Review ArticleThe Great Healing Potential Hidden in Plant Preparations ofAntioxidant Properties: A Return to Nature?

Małgorzata Kiełczykowska and Irena Musik

Chair and Department of Medical Chemistry, Medical University of Lublin, 4A Chodźki Street, 20-093 Lublin, Poland

Correspondence should be addressed to Małgorzata Kiełczykowska; malgorzata.kielczykowska@umlub.pl

Received 29 July 2020; Revised 20 August 2020; Accepted 12 September 2020; Published 10 October 2020

Academic Editor: Patricia Morales

Copyright © 2020 Małgorzata Kiełczykowska and Irena Musik. This is an open access article distributed under the CreativeCommons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided theoriginal work is properly cited.

The application of chemicals in industry and agriculture has contributed to environmental pollution and exposure of livingorganisms to harmful factors. The development of new pharmaceutical agents enabled successful therapy of various diseases, buttheir administration may be connected with side effects. Oxidative stress has been found to be involved into etiology ofnumerous diseases as well as harmful action of drugs and chemicals. For some time, plant origin substances have been studiedas potential protective agents alleviating toxicity of various substances and symptoms of diseases. The aim of the current reviewwas to present the diversity of the research performed during the last five years on animal models. The outcomes showed a hugeprotective potential inherent in plant preparations, including alleviating prooxidative processes, strengthening antioxidantdefence, ameliorating immune parameters, and reversing histopathological changes. In many cases, plant origin substances wereproved to be comparable or even better than standard drugs. Such findings let us suggest that in the future the plantpreparations could make adjuvants or a replacement for pharmaceutical agents. However, the detailed research regarding doseand way of administration as well as the per se effects needs to be performed. In many studies, the last issue was not studied,and in some cases, the deleterious effects have been observed.

1. Introduction

In the recent centuries, a great change of the conditions of thehuman life has taken place, due to the development of indus-try, agriculture, medicine, and pharmacy. The new syntheticsubstances were applied to protection of crops as well as suc-cessful therapy of various diseases. However, except for ben-eficial influence, consisting in numerous facilitations ofhuman existence and extending human life span, negativeeffects have also occurred [1, 2]. A growing pollution of nat-ural environment, resulting from the industry development,has been observed for many years [3–5]. Despite the effortsaiming at alleviating and preventing this phenomenon, it stillbelongs to the most important problems to be solved by themankind. The application of plant protection products hasmade another contribution to environmental contamination[6–9]. As it is not possible to improve the situation immedi-ately, many people, i.e., industrial workers or farmers are still

exposed to harmful substances like heavy metals [4, 10–12],organic chemicals (e.g., CCl4) [13, 14], or pesticides and plantgrowth regulators [8, 15]. Another problem results fromintroducing plenty of new pharmaceutical agents. Theyallowed to relieve suffering of many subject and successivetreatment in cases of mortal diseases. However, on the otherhand, plenty of side effects have also been observed [16, 17].Analgesic and antipyretic drugs like acetaminophen or aspi-rin can induce liver and kidney damage [18–22]. The anti-neoplastic agents can cause severe disturbances liketesticular damage [23], nephrotoxic [16, 24], cardiotoxic[25, 26], and hepatotoxic [27] effects. Antibiotics have alsoproved to show side effects including liver and kidney dam-age [28, 29]. The widespread practice of using different addi-tives to preserve and improve the taste of food makes anothersource of toxic action on human organisms [30]. The grow-ing life span is connected with an increase in incidence ofneurodegenerative disorders like Parkinson’ disease [31] or

HindawiOxidative Medicine and Cellular LongevityVolume 2020, Article ID 8163868, 55 pageshttps://doi.org/10.1155/2020/8163868

Alzheimer’s disease [32]. Furthermore, in the recent decades,obesity, hyperlipidemia, and connected disturbances havebecome a significant worldwide problem [33, 34].

All the presented facts have made the scientists searchfor any agents which could exert protective effects againsttoxic environmental pollutants and chemicals used inindustry and agriculture and replace the standard drugsor make beneficial adjuvants. The return to natural prod-ucts, sometimes used for thousands years in traditionalmedicine, has become one of the significant directions ofthis research [35–39]. It could be stated, without any exag-geration, that “a great return to nature” is recently beingobserved. Plant extracts and plant origin substances per sedo not show so many side effects as pharmacological sub-stances. On the other hand, they contain numerous com-pounds of anti-inflammatory and antioxidative propertieslike polyphenolic derivatives and flavonoids [40–42]. Thepresented facts prompted large-scale research on possibili-ties of application of plant preparations as protective agentsagainst toxicity of various substances as well as adjuvantsalleviating the symptoms of diseases, obesity, and traumata[6, 25, 38, 43–49]. A great quantity of plant species havebeen investigated, and the obtained results seem to be verypromising. Some studies have included the comparison ofthe investigated materials with standard drugs, and the out-comes suggest that in many cases the replacement would bepossible [20, 31, 35, 50–53]. However, many questionsremain to be solved as to the best way of treatment andthe most beneficial dose.

Oxidative stress—the disturbed balance between genera-tion of reactive oxygen species (ROS) and antioxidants’ levelin an organism—has been found to be involved, less or more,into the etiology of most diseases [54–56]. This processinvolves the generation of ROS, active particles capable ofinjuring all bioactive compounds—protein, lipids, andnucleic acids in an organism. Lipid peroxidation caused byROS may lead to damage of membrane lipids. Living organ-isms developed a wide range of endogenous substances, bothenzymatic and low-molecular ones, which can neutralizeROS. Negative effects resulting from stress, exposure totoxic substances, side effects of the standard drugs, or evenfood supplements have also been proved connected withprooxidative processes and deterioration of antioxidantdefence [13, 30, 40, 57, 58]. Plant origin preparations, inturn, have been found to exert a strong antioxidant actiondue to high content of components of antioxidative proper-ties. Numerous studies have revealed their direct influenceon oxidative processes by reducing lipid peroxidation orprotein carbonylation as well as increase in antioxidantenzymes’ activities and low-molecular antioxidant concen-trations [34, 43, 59, 60].

Different pathways involved in oxidative and inflamma-tory processes have been found to be affected in the courseof protective action of plant preparations.

The studies have shown the involvement of Nrf2 andKeap1 proteins. Nrf2 is regarded as a key transcription factormediating the endogenous antioxidant response, and Keap1is its negative regulator. Under oxidative stress conditions,Nrf2 is released and translocated to the nucleus where it

binds to ARE regions in DNA and stimulates antioxidantenzyme gene expression. Both Nrf2 and Keap1 as wellproteins regulated by Nrf2, responsible for defence againstantioxidant stress like HO-1 and γ-GCS, have been foundto be disturbed by harmful factors (cadmium or high-fat diet)and regulated by plant preparations [12, 61]. Plant originsubstances have been reported to cause upregulation ofNrf2, HO-1, and γ-GCS in both nonexposed and Pb-exposed rats [62].

Another pathway connected with oxidative and inflam-matory processes which have been proved involved into pro-tective properties of plant preparations is NF-κB pathway.NF-κB is a transcription factor responsible for expression ofproinflammatory cytokines [56]. Its activation can be trig-gered by TLR receptors, belonging to pattern recognitionreceptors. The inflammation and redox balance have beenfound to be strongly connected with each other [63]. Inter-leukins, γ-interferon and tumour necrosis factor, have beenfound to affect ROS production [64]. The involvement ofthe LPS-TLR4-NF-κB pathway into protective action of plantmaterials has been reported [56, 65]. Other authors havestated that a protective effect of a plant extract, resulting fromantioxidative and anti-inflammatory influence observed indiabetes animal model, could be attributed to inhibition ofNF-κB activation [66].

Mitogen-activated protein kinases (MAPK) belong toenzymes which make mediators of various processes occur-ring in cells like death, proliferation, or differentiation. TheMAPK pathway begins from a signal from an extracellularreceptor and through a cascade of subsequent protein phos-phorylation leads to activation of different proteins includingtranscription factors (e.g., p53 protein) and finally to theexpression of genes. ROS have been proven to be connectedwith particular steps of the MAPK pathway. There are threekinds of MAPK in mammals: p38 MAPK, ERK1 (extracellu-lar signal-regulated kinase 1), and JNK (c-Jun N-terminalkinase) [64, 67]. The studies on plant revealed the influenceof the studied plant materials on some elements of the MAPKpathway [42].

The next pathway connected with oxidative stress whichhas been found affected by plant preparations is the JAK/-STAT pathway. An outside signal, usually being a cytokine,binds to a membrane receptor resulting in its dimerization.The next stage is the activation of JAK which renders possiblephosphorylation of receptor, which in turn enables STATbinding and phosphorylation. Activated by phosphorylationSTAT is then translocated into the nucleus where it acts as atranscription factor [68]. The relationships between thispathway and ROS have been reported [69]. In the currentstudy, disturbances of oxidative balance as well as bone mar-row damage and reduction in pJAK2/JAK2 and pSTAT5a/S-TAT5a, caused by radiation exposure, have been found to beimproved by a plant preparation, which made the authorssuggest that the studied material can stimulate the JAK2/-STAT5a signal pathway [70].

The aim of the current review is to present the results ofthe studies performed in the last five years regarding the pro-tective and medicinal properties of plant origin preparationswith particular emphasis on their antioxidant action.

2 Oxidative Medicine and Cellular Longevity

2. The Protective Properties of PlantPreparations against Toxicity ofVarious Factors

2.1. The Protective Influence of Plant Preparations againstChemicals Applied in Agriculture. The use of different che-micals in food production has been growing dramaticallyin the recent years, causing the contamination of the natu-ral environment and increasing thread to human health.Neurotoxicity, hepatotoxicity, reproductive disturbances,and cancerogenesis belong to the negative effects exertedon organisms [6, 8, 15, 71]. Moreover, chemicals of lipo-philic character can be accumulated in membranes [9].Enhanced generation of ROS was proved involved into theirharmful influence [6, 9, 71]. Plant origin materials wererevealed to show protective properties not only by strength-ening the antioxidant barrier but also by reversing histo-pathological changes. A wide range of different materialswas studied, including simple extracts [2, 6, 7] as well ascommercial products [9, 15]. The saponins from Tribulusterrestris, which were reported to possess antiaging action,were found to exert protective effects against rotenone-induced parkinsonism [15].

The details concerning the above mentioned studies arepresented in Table 1.

2.2. The Protective Influence of Plant Preparations againstToxic Effects of Heavy Metals. Environmental pollution withheavy metals makes a great global problem. The most toxicones are lead, cadmium, and mercury. Even low concentra-tions can cause severe disturbances of organism, includingbrain, hepatic, renal, and reproductive damage [10]. As theirharmful action is connected with oxidative stress induction,plant extracts showing antioxidant properties were studiedas possible protective agents and the obtained results werefound to be promising [10, 11], although the accumulationof a toxic metal could not be prevented in every case [62].

The ability of plant origin substances proanthocyanidinsto prevent lead-induced hepatotoxicity was suggested to beconnected with the Nrf2/ARE pathway (as an increase ofmRNA expression levels of Nrf2 in the liver of mice admin-istrated with proanthocyanidins and/or lead was observed)as well as with the reduction of endoplasmatic reticulumstress via a decrease in stress-related proteins GRP78 andCHOP [62].

In the experiments concerning the toxicity of mercury,plant extracts relieved the negative effects in the case of bothan inorganic form (mercury (II) chloride) and organic one(dimethylmercury); at the same time, the beneficial influenceincluded not only oxidant and immunological parametersbut also histopathological changes [4, 72, 73].

Plant extracts were also found to exert wide protectiveeffects against the third most dangerous heavy metal cad-mium, with the results being confirmed by in vitro studieswith using murine hepatocytes [3]. Additionally, an animalstudy showed the involvement of the Nrf2/Keap1 pathwayinto the protective action of Pyrantha fortuneana extract asthe plant material, given both alone and coadministered withcadmium caused a significant increase in expression of Nrf2

and decrease in expression of Keap1 in the kidneys of ratsvs. the control and Cd-exposed group, respectively [12].

Apart from lead, mercury, and cadmium the researchconcerning metals’ toxicity included also liver injury causedby iron overload. 70% methanol extract of Droseraburmannii Vahl. showed a distinct, dose-dependent efficacyagainst iron-induced hepatoxicity. This effect, particularlyin case of the highest dose, was comparable with that exertedby a standard drug desirox—an iron chelator. Additionally,the studied extract studied in vitro showed the ability to che-late Fe2+ ions. Such findings made the authors suggest thatthe studied preparation might be used as a medicine in cureof iron overload-induced diseases [50].

The details concerning the above-mentioned studies arepresented in Table 2.

2.3. The Protective Influence of Plant Preparations againstVarious Chemicals. Plant origin substances, extracts andtheir particular fractions, essential oils, and seed powderswere found to reverse or alleviate disturbances of organismresulting from exposure to different chemicals. The resentresearch included various compounds, e.g., hepatotoxic tet-rachloromethane (CCl4) used for years as a solvent andnow regarded as an environmental pollutant [14], alumin-ium known for its neurotoxicity [74], aflatoxins producedby toxigenic fungi which made food contaminants [75],and chemicals used in industry and laboratory experimentslike thioacetamide [76] or 1-chloro-2,4-dinitrobenzene[77]. Additionally, plant origin substances were proved todecrease mouse mortality resulting from the acute CCl4 tox-icity [78] as well as from Concanavalin A exposure [79]. Fur-thermore, several studies included the influence of plantmaterials alone, and generally, no harmful effects wereobserved [14, 54, 74, 75, 78, 80, 81].

The details of the performed studies are presented inTable 3.

2.4. The Protective Influence of Plant Preparations againstCarcinogens. Plant extracts were studied using animal modelas for their possible application in tumour therapy due to thepresence of anticancer and antioxidant components. Thenecessity of searching for new agents, suitable for tumourtreatment, was challenged by the lack of effective chemother-apy and severe side effects associated with the used medi-cines. The obtained results seem to be promising as thestudied materials alleviated carcinogen-induced oxidativestress as well as disturbances of immunological parameters[47, 88, 89]. Histolopathological studies confirmed the bene-ficial effects of the investigated preparations [46, 89].

The detailed results of the performed studies are pre-sented in Table 4.

2.5. The Protective Influence of Plant Preparations againstEthanol. Alcohol excessive consumption and addiction leadsto different negative effects: liver injuries including steatosis[56, 91], brain damage [92], and reproductive system damage[93]. The disturbances of oxidative balance were suggested tobe one of the factors underlying alcohol toxicity, which wasconfirmed by intensification of lipid peroxidation as well as

3Oxidative Medicine and Cellular Longevity

Table1:The

protective

prop

erties

ofplantextractsagainsttoxicity

ofsubstances

appliedin

agricultu

re.

Reference

Plant

preparation,

dose,w

ayandtimeof

treatm

ent,

anim

als

The

toxicsubstance,do

se,w

ayand

timeof

expo

sure,and

negative

effects

Protectiveeffectsof

plantpreparation

Effectsof

plantperse

Chaâbaneetal.

[6]

Nitrariaretusa

fruitaqueou

sextract

Pretreatm

entfor6days

andtreatm

entdu

ring

pencon

azoleexpo

sure

300mg/kg

b.w.,p.o.,d

aily

MaleWistarratsabou

t250g

Afungicidepencon

azole-indu

ced

kidn

eyinjury

67mg/kg

b.w.(1/30

LD50)i.p.,every

2days

from

7thun

til15thday

Plasm

a:GGT,A

LP↓;CR,u

rea,UA,L

DH

↑

Urine:volum

e↑,CR,u

rea,UA↓

Kidney:LD

H,M

DA,H

2O2,PC,

AOPP,N

P-SH,

GSH

,MT,C

AT,SOD,G

Px↑

Kidney:enlarged

Bow

man’sspace,

necrosisof

theepithelial

cells

liningthetubu

les,infiltrationof

leucocytes,glomeruli

fragmentation

↑

Plasm

a:ALP

(+),urea,L

DH,G

GT(++),

CR,U

A(+++)

Urea:UA(+),volume,CR,u

rea(++)

Kidney:LD

H,M

DA,H

2O2,PC,

AOPP,N

P-SH,

GSH

,CAT,SOD,G

Px(++),MT(+++)

Kidney:necrosisof

theepithelial

cells

liningthetubu

les(++),

enlarged

Bow

man’sspace,

infiltrationof

leucocytes,glomeruli

fragmentation

(+++)

Plasm

a:urea,L

DH

↑Urine:volum

e↑,CR,

urea

↓

Alzahrani

etal.

[15]

Standardized

Tribu

lusTerrestris

extracttablets

1000

mg(m

in.45%

sapo

nins)

Now

SportsCo.(U

SA)

5or

10mg/kg

daily,p

.o.,

for17

days

MaleSw

issalbino

mice,

20-28g

Apesticideroteno

ne-ind

uced

parkinsonism

,

nine

dosesof

1mg/kg

giveneach

48±2h

,s.c.

Activityindex(18thday)

↓

Substantianigra:%

ofpycnoticneuron

s↑,

%of

viableneuron

s↓

Striatum

:relativeexpression

ofiNOS,

COX-2

andMTH

1,MDA,8-O

H-dG↑,

dopamine,GSH

,SOD,C

AT↓

Activityindex(18thday)

(+5,+++10)

Substantianigra:%

ofviableneuron

s

(+50,+

++10),

%of

pycnoticneuron

s

(++5,+++10)

Striatum

:GSH

,SOD,M

DA(0

5,++10),

CAT

(05,+++10),do

pamine(+

5,++10),

relative

expression

ofCOX-2

andiNOS

(++both

doses),

8-OH-dGandrelative

expression

ofMTH

1

(++5,+++10)

Non

e

Selm

ietal.[71]

Lavand

ulastoechas

essentialo

ils50

mg/kg

b.w.,p.o.,for

30days

Malemice,

8-weekold,

25-30g

Malathion

(apesticide)

200mg/kg

b.w./d

ayfor30

days,p

.o.

Serum:T

↓

Testis:relative

weight,MDA,H

2O2↑,

-SH

grou

ps,G

Px,CAT,SODtotal,

Cu/Zn-SO

D,

Mn-SO

D↓

Epididymis:relativeweight,MDA,

H2O

2↑,-SH

grou

ps,G

Px,CAT,

Serum:T

(+++)

Testis:Mn-SO

D(0),-SH

grou

ps,

SODtotal(++),

relative

weight,MDA,H

2O2,GPx,

Cu/Zn-SO

D,C

AT(+++)

Epididymis:C

ATandH

2O2(++),

relative

weight,MDA,-SH

grou

ps,G

Px,

SODtotal,Cu/Zn-SO

D,M

n-SO

D(+++)

Testis:CAT↑

4 Oxidative Medicine and Cellular Longevity

Table1:Con

tinu

ed.

Reference

Plant

preparation,

dose,w

ayandtimeof

treatm

ent,

anim

als

The

toxicsubstance,do

se,w

ayand

timeof

expo

sure,and

negative

effects

Protectiveeffectsof

plantpreparation

Effectsof

plantperse

SODtotal,

Cu/Zn-SO

D,M

n-SO

D↓

ElA

rem

etal.[7]

Phoenixdactylifera

L.datepalm

fruit

aqueou

sextract

4mL/kg

daily,p

.o.,

for2mon

ths

MaleWistarrats180–200g

Dichloroaceticacid

(afungicide)

0.5g/Lor

2g/Las

drinking

water,

for2mon

ths

0.5g/L:

Weight:testes,epididymis↓

Plasm

a:T,F

SH,L

H↓

Testes:CAT,SOD,L

PO

↑,GSH

↓2g/L:

Weight:testes,epididymis↓

Plasm

a:T,F

SH,L

H↓

Testes:CAT,SOD,L

PO

↑,GSH

,GPx↓

0.5g/Lof

dichloroaceticacid:

Weight:testes,epididymis(+++)

Plasm

a:T,F

SH,L

H(+++)

Testes:CAT,SOD,L

PO,G

SH(+++)

2g/Lof

dichloroaceticacid:

Weight:testes

(++),epididym

is(+++)

Plasm

a:T,F

SH,L

H(++)

Testes:CAT,SOD,G

SH,L

PO

(++),

GPx(+++)

Non

e

Mossa

etal.[9]

Vitisvinifera

grapepo

mace(ElK

room

Com

pany,A

lexand

ria,Egypt)

80%

ethano

licextract

100or

200mg/kg

b.w.,p.o.,28

consecutivedays

Weanlingfemaleratsabou

t50

g

Cypermethrin

(aninsecticide)

25mg/kg

b.w.(1/10

ofLD

50),p.o.,for

28consecutivedays

Relativeweight:liver

↓,kidn

ey↑

Serum:T

P,A

LB↓,AST

,ALT

,ALP

,GGT,

urea

nitrogen,C

R↑

Liver:Kup

ffer

cellactivation

,portal

infiltrationwithinflam

matorycells,

hyperplasiaof

biledu

ct,con

gestion

ofcentralveinandhepaticsinu

soids↑

Kidney:vacuolizationof

endo

thelial

liningglom

erular

tuft,vacuo

lization

ofepithelialliningrenaltub

ules,

necrosisof

epithelial↑

Relativeweight:liver,kidney

(+++both

doses);

Serum:A

LT,C

R(++both

doses),A

ST,

ALP

,GGT,T

P(++100,+++200),A

LB,u

rea

nitrogen

(+++both

doses)

Liver:Kup

ffer

cellactivation

(+100,++

200),

portalinfiltration

withinflam

matory

cells,

hyperplasiaof

biledu

ct,con

gestionof

centralveinandhepaticsinu

soids

(+++both

doses)

Kidney:vacuolizationof

endo

thelial

liningglom

erular

tuft(++100,+++200),

vacuolizationof

epitheliallining

renaltub

ules,

necrosisof

epithelial(+++both

doses)

Bothdo

ses:

Liver:Kup

ffer

cell

activation

↑

Mirzaeietal.[2]

Quercus

bran

tii7

0%ethano

lextractof

internal

layerof

thefruit

500mg/kg,p

.o.,for9days

MaleWistaralbino

rats,150-200

g

Carbend

azim

:methyl-2-benzim

idazolecarbam

ate

(afungicideagent),50mg/kg

p.o.,for

9days

Serum:A

LT,A

ST,A

LP,u

reanitrogen,C

R↑

Liver:MDA↑,GSH

↓Kidney:MDA↑,GSH

↓

Serum:A

LT,A

ST,A

LP,u

reanitrogen,

CR(++)

Liver:MDA(+),GSH

(++)

Kidney:MDA,G

SH(++)

Not

stud

ied

5Oxidative Medicine and Cellular Longevity

Table1:Con

tinu

ed.

Reference

Plant

preparation,

dose,w

ayandtimeof

treatm

ent,

anim

als

The

toxicsubstance,do

se,w

ayand

timeof

expo

sure,and

negative

effects

Protectiveeffectsof

plantpreparation

Effectsof

plantperse

Khalafetal.[8]

Punica

gran

atum

L.po

megranatepeel

methano

lextract

250mg/kg

daily,i.g.,

for4weeks

MaleWistarrats,140-160

g

Gibberellicacid-3

(aplantgrow

thregulator)

20mg/kg

i.g.,daily

for4weeks

Testes:area

percentof

androgen

receptor

immun

oreaction,

SOD,C

AT↓

Testes:area

percento

fand

rogenreceptor

immun

oreaction,

SOD,C

AT(+++)

Non

e

↓:adecrease

vs.con

trol;↑:anincrease

vs.con

trol;(+):aslight

beneficialeffect;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect;(0):no

beneficialeffect.

6 Oxidative Medicine and Cellular Longevity

Table2:The

protective

effectsof

plantorigin

substances

againsttoxicity

ofheavymetals.

Reference

Plant

preparation,

dose,w

ayand

timeof

treatm

ent,anim

als

The

toxicsubstance,do

se,w

ayandtimeof

expo

sure,

andnegative

effects

Protectiveeffectsof

plantpreparation

Effectsof

plant

perse

Abd

elMon

eim

[10]

Indigofera

oblongifo

lialeaves

water-m

ethano

l(1:2)extract

100mg/kg

b.w.p

.o.d

aily,1

hbefore

Pbfor5days

MaleWistarrats,8-w

eek-old,

150–180g

Pblead

acetateacutetoxicity,20mg/kg

b.w.d

ailyfor5days,i.p.

Serum:A

ST,A

LT,A

LP,totalbilirub

in,T

C,

TG,L

DL-c↑,HDL-c↓

Liver:relative

weight,Pbaccumulation,

LPO,

NO

andH

2O2,↑,GSH

,SOD,C

AT,G

Px,GR↓

Liver:expression

ofmRNAof

SOD2,CAT,

GPxandBcl-2↓,Bax

andHO-1↑

Serum:A

LP,totalbilirub

in,T

G,H

DL-c(++),AST

,ALT

,TC,L

DL-c(+++)

Liver:relative

weight,Pbaccumulation,

NO,H

2O2,

SOD,C

AT,G

R(++),LP

O,G

SH,G

Px(+++)

Liver:HO-1(-),expression

ofmRNAof

SOD2,CAT,

GPx,Bax,B

cl-2

(++)

Liver:GSH

,GPx↑

Long

etal.[62]

Proanthocyanidins

extractedfrom

grapeseeds(ZelangMedical

Techn

ologyCom

pany,

Nanjin

g,China)

100mg/kg

b.w.,p.o.,sixdays

every

weekfor6weeks

MaleKun

mingmice,3-week-old

Pblead

acetate0.2%

indrinking

water

for6weeks

Blood

:Pb↑

Serum:A

LT,A

ST,A

LP↑

Liver:GSH

,GPxandSO

D↓,relative

mRNA

expression

ofNrf2,γ-GCS,HO-1

slightly↑,Pband

MDAas

wellasrelative

mRNAexpression

ofBax,

GRP78

andCHOP↑,relative

mRNA

expression

ofBcl-2

↓

Blood

:Pb(0)

Serum:A

LT,A

ST,A

LP(++)

Liver:Pb(+),GPx,SO

D,relativemRNAexpression

ofBax,B

cl-2

GRP78,C

HOP(++),MDA,G

SH(+++),

relative

mRNAexpression

ofNrf2,γ-GCS,HO-1

↑

Liver:relative

mRNA

expression

ofNrf2,γ-GCS,

HO-1

↑

El-Boshy

etal.[11]

Thymus

vulgarisleafethano

lextract

500mg/kg/day,p

.o.,for6weeks

Sprague-Daw

leymalerats,

abou

t150g

Pblead

acetate500mg/Lin

drinking

water,for

6weeks

Serum:T

NF-α,IL-1β

,IL-6↑,IN

F-γ,IL-10↓

Liver:Pb,MDA↑,GSH

,GPx,CAT↓

Kidney:Pb,MDA↑,GSH

,GPx,CAT↓

Serum:IL-1β

,IL-6(++),IN

F-γandIL-10(+++)

Liver:Pb(++),MDA,G

SH,G

Px,CAT(+++)

Kidney:Pb(++),MDA,G

SH,G

Px,CAT(+++)

Serum:IL-10

↑Liver:GSH

,GPx↑

Kidney:GSH

,GPx↑

Dua

etal.[3]

Ipom

oeaaqua

tica

andEn

hydra

fluctuan

saerialpartsaqueou

sextracts

Pretreatm

ent

100mg/kg

b.w.,p.o.,for

5days

followed

bycadm

ium

chloride

Swissmalealbino

mice,1-2

mon

ths,20-30g

Cdcadm

ium

chloride,4

mg/kg

b.w.,for6days,

once

daily,p

.o.

Blood

:RBC,H

GB↓

Serum:A

LT,A

ST,u

rea,TC,T

G↑,HDL-c↓

Liver:cadm

ium,R

OS,LP

O,N

ADH

oxidase,protein

carbon

ylation↑,totalcoenzym

esQ9andQ10,C

AT,

SOD,G

ST,G

Px,GR,G

6PD,G

SH↓

Kidney:cadm

ium,R

OS,LP

O,N

ADHoxidase,protein

carbon

ylation↑,totalcoenzym

esQ9andQ10,C

AT,

SOD,G

ST,G

Px,GR,G

6PD,G

SH↓

Heart:cadmium,R

OS,LP

O,N

ADH

oxidase,protein

carbon

ylation↑,totalcoenzym

esQ9andQ10,C

AT,

SOD,G

ST,G

Px,GR,G

6PD,G

SH↓

Brain:cadmium,R

OS,LP

O,N

ADH

oxidase,protein

carbon

ylation↑,totalcoenzym

esQ9andQ10,C

AT,

SOD,G

ST,G

Px,GR,G

6PD,G

SH↓

Testes:cadm

ium,R

OS,LP

O,N

ADH

oxidase,protein

carbon

ylation↑,totalcoenzym

esQ9andQ10,C

AT,

SOD,G

ST,G

Px,GR,G

6PD,G

SH↓

Bothextracts:

Blood

:RBC,H

GB(++)

Serum:A

LTAST

,urea,TC,T

G,H

DL-c(++)

Bothextracts:

Cadmium

burden,R

OS,G6P

D,N

ADPH

oxidase:

liver,kidney,heart,brain,

testes

(++)

LPO:liver,kidney,heart,brain,

testes

(+++);

Protein

carbon

ylation:liver,kidney,heart,testes(++),

brain(+++)

TotalcoenzymeQ9:liver,brain,h

eart,testes(++),

kidn

ey(+++)

TotalcoenzymeQ10:kidney,brain,

testes

(++),liver,

heart(+++)

CAT:liver,brain,h

eart(++),kidn

ey,testes(+++)

SOD,G

ST:liver,kidney,heart,brain,

testes

(+++)

GPx:liver,h

eart,testes(++),brain,

kidn

ey(+++)

GR:h

eart,testes,brain(++),liver,kidney(+++)

GSH

:heart,kidney,brain(++),liver,testes(+++)

Not

stud

ied

7Oxidative Medicine and Cellular Longevity

Table2:Con

tinu

ed.

Reference

Plant

preparation,

dose,w

ayand

timeof

treatm

ent,anim

als

The

toxicsubstance,do

se,w

ayandtimeof

expo

sure,

andnegative

effects

Protectiveeffectsof

plantpreparation

Effectsof

plant

perse

Olaniyan

etal.[1]

Plukenetia

conophoraseeds

methano

lextract

100or

200mg/kg

b.w.,p.o.,for

54days

afterCdC

l 2treatm

ent

MaleWistarrats,150-190

g

Cdcadm

ium

chloride,a

singledo

se2mg/kg

b.w.,i.p.

Serum:T

,LH,F

SH↓

Epididymalsemen:cou

ntof

cells,m

otility,viability↓

Testis:MDAandNO

↑,SO

D,C

AT,G

Px,GST

,Na+/K

+ATPase,Ca2

+ATPase,Mg2

+ATPase↓

Epididymis:M

DAandNO↑,SO

D,C

AT,G

Px,GST

↓

Serum:L

H(0

100,+200),F

SH(+

both

doses),

testosterone

(++100,+++200)

Epididymalsemen:cou

ntof

cells,m

otility,

viability

(++both

doses)

Testis:Mg2

+ATPase(++both

doses),N

a+/K

+ATPase

(++100,+++200),M

DA,N

O,SOD,C

AT,G

ST(+++both

doses),C

a2+ATPase(+++100,↑200),

GPx(↑

both

doses)

Epididymis:G

Px(+

both

doses),SOD,G

ST,

Na+/K

+ATPaseandCa2

+ATPase(++both

doses),

CAT(++100,+++200),M

DA,M

g2+ATPase

(+++bo

thdo

ses),N

O(+++100,↓200)

Not

stud

ied

Mężyń

ska

etal.[5]

Aroniamelan

ocarpa

L.berries

extract(A

damed

Con

sumer

Health

care,T

uszyn,

Poland)

0.1%

aqueou

ssolution

inform

oftheon

lydrinking

fluidfor3,10,17

or24

mon

ths

FemaleWistarrats,3-4-w

eek-old

Cdcadm

ium

chloride

indiet1mg/kg

(Cd 1)or

5mg/kg

(Cd 5)for3,10,17or

24mon

ths

Liver:SO

D(Cd 1

3,10,17m)and(Cd 5

17m)↓;CAT

(Cd 5

17m)↓;

GPx(Cd 1

3,10,17,24

m),(Cd 5

3,10,17,24

m)↓;GR

(Cd 1

10,24m),(Cd 5

10,17m)↓;GST

(Cd 1

3,10,

17m),(Cd 5

3,10,17m)↓;GSH

/GSSG(Cd 1

17m),

(Cd 5

10,17m)↓;H

2O2(Cd 1

10,17,24

m),(Cd 5

10,

17,24m)↑;OSI

(Cd 1

10,17m),(Cd 5

3,10,17,24

m)

↑;MDA(Cd 1

10,17,24

m),(Cd 5

10,17,24

m)↑

Liver:SO

D:C

d 1(+

3m,0

10m,+

++17

m),

Cd 5

(+++17

m)

CAT:C

d 5(++17

m)

GPx:Cd 1

(+++3,10

m,+

+17,24m),

Cd 5

(03m,+

+10

and17

m,+

++24

m)↓

GR:C

d 1(+++10

m,↑

24m),

Cd 5

(++1m,-

17m)

GST

:Cd 1

(+++3,10,17m),Cd 5

(++3m,0

10m,+

++17

m)

GSH

/GSSG:C

d 1(+++1m),Cd 5

(+++10

m,↑

17m)

H2O

2;Cd 1

(+++10,17,24

m),Cd 5

(+++10,17,24

m)

OSI:C

d 1(+++10,17m),Cd 5

(+++3,10,17,24

m)

MDA:C

d 1(+++10,17,24

m),Cd 5

(+++10,17,24

m)

Liver:CAT10m

↓,GR3m

↓,GSH

/GSSG

24m

↑

Keetal.[12]

Pyracantha

fortun

eana

fruits60%

ethano

lextract

Pretreatm

ent,1hbeforecadm

ium,

250mg/kg,p

.o.,for5days

MaleWistarrats,7-8-w

eek-old,

150-170g

Cdcadm

ium

chloride,6.5mg/kg

daily

for5days,i.p.,

Bod

yweightgain

↓Kidneyweight↑

Plasm

a:UA,u

reaandCR↑

Kidney:Cdaccumulation,

MDA,N

O,expressionof

Keap1,B

axandTNF-αprotein↑,CAT,G

Px,GSH

,SO

D,G

R,expressionof

Bcl-2,H

O-1,γ-G

CS,NQO1

andNrf2protein↓

Bod

yweightgain

(++)

Kidneyweight:(++)

Plasm

a:urea,U

AandCR(++)

Kidney:Cdaccumulation,

MDA,N

O,C

AT,G

Px,

GSH

,SOD,G

R(++),expression

ofBcl-2,B

axand

TNF-αprotein(++),expression

ofKeap1,H

O-1,γ-

GCS,NQO1andNrf2protein↑

Kidney:

expression

ofKeap1,H

O-1,γ-

GCS,NQO1,

Nrf2↑

Kim

etal.[73]

Dendropan

axmorbifera

leaf80%

ethano

lextract

100mg/kg,p

.o.,daily

for4weeks

MaleSprague-Daw

leyrats,

7-week-old

Hgdimethylm

ercury

daily

5μg/kg,i.p.,for4weeks

Hippo

campu

s:Hgconcentration,

ROSprod

uction

,GST

,MDA↑,SO

D1,totalsulfhydrylcon

tent,

CAT,G

Px,GR↓

Hippo

campu

s:CAT,totalsulfh

ydrylcon

tent

(+),

Hgconcentration,

ROSprod

uction

,MDA,

SOD1,GST

,GPx,GR(++)

Non

e

8 Oxidative Medicine and Cellular Longevity

Table2:Con

tinu

ed.

Reference

Plant

preparation,

dose,w

ayand

timeof

treatm

ent,anim

als

The

toxicsubstance,do

se,w

ayandtimeof

expo

sure,

andnegative

effects

Protectiveeffectsof

plantpreparation

Effectsof

plant

perse

Jahanetal.[72]

Chenopodium

albu

mLinn

.seed

ethano

lextract

200mg/kg

b.w.,p.o.,for

30days

Sprague-Daw

leymalerats,

abou

t240g

Hgmercury(II)chloride,0.15mg/kg

b.w.for

30days,i.p.

Bod

yweight↓

Plasm

a:BUN,C

R,cho

lesterol,T

G,L

DL↑,HDL,

T↓

Testiculartissue:T

P,C

AT,SOD,G

ST↓,

ROSandTBARS↑

Dailysperm

prod

uction

:↓

Bod

yweight(+++)

Plasm

a:cholesterol,TG(-),LD

L,CRand

HDL(++),BUN

andT(+++)

Testiculartissue:T

P,C

AT,SOD,G

ST,

ROSandTBARS(++)

Dailysperm

prod

uction

:(+++)

Non

e

Gao

etal.[4]

Rheum

palm

atum

L.driedroot

andRhizoma(Lixian

Pharm

aceuticalsCom

pany,

Longnan,

China)60%

ethano

lextract

1200

mg/kg,i.g.,daily

for7days

Sprague-Daw

leymalerats,

140–160g

Hgmercury(II)chloride,a

singledo

seof

2mg/kg,s.c.,on

the5thday

Bod

yweight:↓

Serum:T

P,A

LB↓BUN,C

R↑

Kidney:GSH

,GPxandCAT↓

Renaltubu

leepithelialcells:swellin

g,necrosis,

granular

degeneration

,interstitial

vascular

congestion

↑

Bod

yweight:(++)

Serum:A

LB,C

R,B

UN

(++);TP(+++)

Kidney:GPx,CAT(0),GSH

(+)

Renaltubu

leepithelialcells:swellin

g(+),

necrosisgranular

degeneration

,interstitial

vascular

congestion

(++)

Not

stud

ied

Ghateetal.[50]

Drosera

burm

anniiV

ahl.70%

methano

lextract

50,100,or200mg/kg

b.w.,p.o.,for

21days

from

thenext

dayafter

firstinjectionof

iron

dextran

MaleSw

issmice,

20g

Iron

-dextran

100mg/kg

b.w.,i.p.,

five

doses(one

dose

everytwodays)

Serum:A

LT,A

ST,A

LP,bilirubin,

ferritin

↑Liver:SO

D,C

AT,G

ST,G

SH↓,LP

O↑

Serum:bilirubin(+

50,+

+100+++200),

ALT

andAST

(++alld

oses),ALP

and

ferritin

(++50

and100,+++200)

Liver:SO

D(0

50,+

+100,+++200);C

AT,

GST

,and

LPO

(+++alld

oses);

GSH

(050,+

+100and200)

Not

stud

ied

↓:adecrease

vs.con

trol;↑:anincrease

vs.con

trol;(+):aslight

beneficialeffect;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect;(0):no

beneficialeffect;(-):intensification

oftheharm

fuleffect.

9Oxidative Medicine and Cellular Longevity

Table3:The

protective

effectsof

plantpreparations

againsttoxicity

ofdifferentchem

icals.

Reference

Plant

preparation,

dose,w

ayandtimeof

treatm

ent,

andanim

als

The

toxicsubstance,do

se,w

ayandtime

ofexpo

sure,and

negative

effects

Protectiveeffectsof

plantpreparation

Effectsof

plantperse

AlSaidetal.[13]

Pipercubeba

fruits

70%

ethano

lextract

Pretreatm

ent250or

500mg/kg

for7days,p

.o.

MaleWistaralbino

rats180–200g

CCl 4-ind

uced

hepatotoxicity,a

singledo

seof

0.4mL/kg,i.p.

Serum:A

LT,A

ST,G

GT,A

LP,bilirubin,

LDH

↑Liver:MDA↑,NP-SH,C

AT,T

P↓

Liver:mRNAexpression

ofTNF-α,IL-6,IL-10,HO-1,

iNOS↑

Serum:A

LT,A

ST,L

DH

(0250,++500),

GGT(+

250,++500),A

LP,bilirubin

(++both

doses)

Liver:TP(0

250,++500),M

DA,C

AT

(+250,++500),N

P-SH

(++250,+++500)

Liver:mRNAexpression

ofIL-10(↑

both

doses),

TNF-α,IL-6,HO-1,iNOS(++)

Not

stud

ied

Bellassou

edetal.[14]

Menthapiperita

L.leaf

essentialo

ilPretreatm

ent

5,15,and

40mg/kg

b.w.,daily

for7days,p

.o.

MaleWistarrats

200–220g

CCl 4:1

mL/kg

b.w.onthe7thday,i.p.

Serum:A

LT,A

ST,A

LP,L

DH,G

GT,T

C,T

G,L

DL,

urea,C

R↑,HDL↓

Liver:LP

O,infl

ammatorycells

andcellu

larnecrosis↑,

SOD,C

AT,G

Px↓

Kidney:LP

O,glomerular

andepithelialcellsof

the

proxim

altubu

lesnecrosis↑,SO

D,C

AT,G

Px↓

Serum:A

LT,A

ST,A

LP,LDH,G

GT,T

C,T

G,H

DL,

LDL,

urea,C

R(+

5,++15,40)

Liver:inflam

matorycells

andcellu

larnecrosis,LPO,

SOD,C

AT,G

Px(+

5,++15,and

40)

Kidney:LP

O,SOD,C

AT,G

Px,glom

erular

and

epithelialcellsof

theproxim

altubu

lesnecrosis(+

5,++15,and

40)

40mg/kg

b.w.only

stud

ied:

none

Simeono

vaetal.[54]

Astragalusmonspessulanu

sL.

n-bu

tano

lic

extract—

obtained

bysuccessive

extraction

of80%

methano

lextractwithCH

2Cl 2,ethylacetate,

andn-bu

tano

l

Pretreatm

ent

100mg/kg,for

7days,p

.o.

MaleWistarrats

200–220g

CCl 4-ind

uced

hepatotoxicity

asingledo

se1.25

mL/kg

of10%

CCl 4in

oliveoil

Serum:A

LT,A

ST,A

LP↑

Liver:MDA↑,GSH

,CAT,SOD,

GPx,GR,G

ST↓

Serum:A

LT,A

ST,A

LP(+++)

Liver:GR,G

SH,C

AT,G

Px,GST

(++),

MDA,SOD

(+++)

Non

e

Shah

etal.[80]

Com

melinanu

difloraL.

methano

lextract

Pretreatm

entfor12

days

and2-day-treatm

ent

150,300,450mg/kg

b.w.,p.o.

MaleSpragueDaw

leyrats,150–250

g

CCl 41.0mL/kg

b.w.,twodo

seson

13thand14

thdays

Serum:A

LT,A

ST↑

Liver:GSH

,GST

,GPx,GR,C

AT,G

6PD,Q

R↓,LP

O,

HNE-m

odified

proteinaddu

cts,8-OHdG

,TNF-α,IL-

6,PGE2↑

Serum:A

LT,A

ST(++alld

oses)

Liver:GSH

,GST

,GR,C

AT,G

6PD,

QR,L

PO,H

NE-m

odified

proteinaddu

cts,

8-OHdG

,TNF-α,IL-6,PGE2(++alld

oses),

GPx(++150,+++300,450)

450mg/kg

b.w.only

stud

ied:

none

Yoshiokaetal.[78]

Sasa

veitchiileafextract

Pretreatm

ent0.2mL(1

mLmadefrom

2.82

gof

leaves)for7days

once

perday,p.o.

Maledd

Ymice,7weeks

CCl 43g/kg

asingleinjection,

i.p.

Plasm

a:ALT

,AST

,BUN,C

R↑

Liver:MDA,C

a↑

Kidney:MDA↑

Plasm

a:ALT

,AST

,BUN

(++),

CR(+++)

Liver:MDA,C

a(++)

Kidney:MDA(+)

Non

e

10 Oxidative Medicine and Cellular Longevity

Table3:Con

tinu

ed.

Reference

Plant

preparation,

dose,w

ayandtimeof

treatm

ent,

andanim

als

The

toxicsubstance,do

se,w

ayandtime

ofexpo

sure,and

negative

effects

Protectiveeffectsof

plantpreparation

Effectsof

plantperse

Linetal.[82]

Chenopodium

form

osan

umKoidz

(red

quinoa):

who

leseed

powder,50%

ethano

licbran

extract,

aqueou

sbran

extract

5.13

g/kg

ofredqu

inoa

who

leseed

powder

(rutin

8.46

mg/kg/day),p.o.

1.54

g/kg

ofredqu

inoa

bran

50%

ethano

lextract(rutin

16.4mg/kg/day),p.o.

1.54

g/kg

ofredqu

inoa

bran

water

extract

(rutin

3.92

mg/kg/day),p.o.

MaleBALB

/cmice

CCl 40.5mL/kg

b.w.,twotimes

weekly(Thu

rsdayand

Sund

ay)for6weeks,i.p.

Serum:A

ST,A

LT,T

P,A

LB,

globulins,bilirub

in,C

R,B

UN

↑,ALP

↓Liver:TBARS,ROS,TNF-α,T

GF-β1,

IL-6

↑,SO

D,C

AT↓

Who

leseed

powder:

Serum:A

LP(0),CR,BUN,A

LB,globu

lins(+),ALT

,TP,bilirubin(++),AST

(+++)

Liver:TBARS,ROS,TNF-α,T

GF-β1,IL-6,SOD,

CAT(+++)

Ethanol

bran

extract:

Serum:A

LP(↓),ALB

,globu

lins,BUN(+),CR,A

LT,

AST

,TP,bilirubin(++)

Liver:TGF-β1(+),ROS(++),TBARS,TNF-α,

IL-6,C

AT(+++),SO

D(↑)

Water

bran

extract:

Serum:B

UN,A

LP(0),CR,bilirubin,ALB

,globu

lins

(+),ALT

,AST

,TP(++)

Liver:CAT,T

GF-β1,ROS(+),IL-6

(++),TBARS,

TNF-α(+++),SO

D(↑)

Not

stud

ied

Parvezetal.[83]

Solanu

msurattense

leaves

70%

ethano

lextract

100and200mg/kg

b.w.,p.o.,for

3weeks

MaleWistarrats,8-9-w

eek-old,

200-220g

CCl 4in

liquidparaffin(1:1)

1.25

mL/kg

b.w.,i.p.

Serum:A

ST,A

LT,A

LP,G

GT,bilirubin,

TC,T

G,

LDL,

VLD

L↑;TPandHDL↓

Liver:MDA↑,NP-SH

↓

Serum:A

ST(0

100,+200),T

P,H

DL

(0100,++200),G

GT,L

DL,

VLD

L(+

100,++200)

ALT

,ALP

,bilirubin,

TC,

TG(++both

doses)

Liver:MDA(0

110,++200),N

P-SH

(++both

doses)

Not

stud

ied

Bahcecioglu

etal.[76]

Pistacia

terebinthu

scoffee

(coff

eebranded

“Harpu

tÇedeneCoff

ee”)

Freshlyprepared

coffee

indrinking

water

(the

contentincreasedby

25%

during

each

preparation,

reaching

upto

100%

atthe

endof

7days),for8weeks

MaleSprague-Daw

leyratsabou

t250g

Thioacetamide-indu

cedchronic

liver

injury,100

mg/kg

b.w.,i.p.,

threetimes

weeklyfor8weeks

Plasm

a:MDA↑

Liver:TNF-α,N

F-κB

,TGF-β↑

Liver:inflam

mation,

necrosis,fi

brosis↑

Plasm

a:MDA(+)

Liver:TNF-α,N

F-κB

,TGF-β(++)

Liver:inflam

mation,

necrosis,fi

brosis(++)

Liver:

TGF-β↓

Tho

maz

al.[84]

Eugeniadysentericaleafhydroalcoh

olicextract

10,100,300

mg/kg/day,p

.o.,for45

days

starting

from

the45

thdayof

AlCl 3administration

MaleSw

issmice,25-30g

AlCl 3-ind

uced

neurotoxicity

100mg/kg/day

p.o.,for

90days

Brain

cortex:M

DA↑,SO

D↓

Hippo

campu

s:MDA↑,CAT,SOD

↓Hippo

campu

sCA1area:%

ofviableneuron

s↓,%

of

necroticneuron

s↑

Brain

cortex:M

DAandSO

D(+++)alld

oses

Hippo

campu

s:CAT(0

10,+

++100and300),M

DA

andSO

D(+++alld

oses)

Hippo

campu

sCA1area:

%of

viableneuron

s(+++10,+

+100,and300),

%of

necroticneuron

s(0

10,+

+100,and300)

Not

stud

ied

Feng

etal.[74]

Defattedwalnu

tmeal(Shaanx

iSea

EcologicalA

griculture

Co.,L

td.,Shangluo

,China)

proteinhydrolysates

1g/kg

perday,for90

days,i.g.,

Malewild

-typeKun

mingmice,8weeks

Neurotoxicityindu

cedby

D-galactose200mg/kg/day,

s.c.(6

hoursafterplantmaterial),and

AlCl 3

(100

mg/kg

inthedrinking

water)for90

days

Brain:SOD,G

Px,ChA

T↓,MDA,A

chE,

TNF-α,IL-1β

↑

Brain:SOD,G

Px,ChA

T(++),

MDA,A

chE,T

NF-α,IL-1β

(+++)

Non

e

11Oxidative Medicine and Cellular Longevity

Table3:Con

tinu

ed.

Reference

Plant

preparation,

dose,w

ayandtimeof

treatm

ent,

andanim

als

The

toxicsubstance,do

se,w

ayandtime

ofexpo

sure,and

negative

effects

Protectiveeffectsof

plantpreparation

Effectsof

plantperse

Kuk

ongviriyapan

etal.[81]

Antidesmathwaitesian

um95%

ethano

licextractof

thefruitspo

mace

100or

300mg/kg

once

daily,p

.o.

MaleSprague-Daw

leyrats,200-220

g

Nω- nitro-L-argininemethylester-ind

uced

nitricoxide

deficiency,

50mg/kg/day

indrinking

water,for

3weeks

Blood

pressure:SBP,D

BP↑

Plasm

a:MDA,P

C↑,NO3- /NO2-level↓

Carotid

artery:sup

eroxideform

ation↑

Aortictissue:eNOSproteinexpression

↓

Blood

pressure:SBP,D

BP(++both

doses)

Plasm

a:PC(0

100,+++200),M

DA,N

O3- /NO2-

level(++100,+++200)

Carotid

artery:sup

eroxideform

ation

(++100,+++200)

Aortictissue:eNOS(+

100,+++200)

Non

e

Yangetal.[77]

Rum

exjaponicusHou

tt.roots

95%

ethano

licextract

4mg/mLand8mg/mL,

topically

tothe

skin

andears,d

ailyfor3weeks

FemaleBalb/cmice,5-week-old

DNCB-(1-chloro-2,4-dinitrobenzene-)indu

ced

atop

icderm

atitis

200μLof

0.5%

DNCB(inaceton

e-oliveoilm

ixture)

tothedo

rsalskin

andear,on

days

1–3

Ear

thickn

ess↑

Lymph

nodesandspleen

weights↑

Skin:m

astcellnu

mber↑

Ear

thickn

ess:(++both

doses,abetter

effectforahigher

dose)

Weightof

lymph

nodes:(+

4,++8)

Weightof

spleen:(++both

doses)

Skin:m

astcellnu

mber(++both

doses,

abetter

effectforahigher

dose)

Not

stud

ied

Zheng

etal.[85]

Dracocephalum

heterophyllum

95%

ethano

lextract

Pretreatm

ent2hbefore

Con

canavalin

A20

mg/kg

b.w.,i.p.

FemaleBALB

/cmice,6-8-week-old

Con

canavalin

A-ind

uced

hepatitissublethald

ose

15mg/kg

b.w.,i.v.

Serum

8,16,and

24ho

ursafterCon

canavalin

A:A

LT,

AST

,IFN

-γ,T

NF-α↑

Liver:MDSC

s↓,Kup

ffer

cells

↑

Serum

8,16,and

24ho

ursafter

Con

canavalin

A:A

LT,A

ST,IFN

-γ,

TNF-α(++)

Liver:Kup

ffer

cells

(+++),MDSC

s↑

Liver:

Kup

ffer

cells

↑

BadrandNaeem

[75]

Physalisperuvian

acape

goldenberry

fruitpo

wder

20%

(w/w

)fruitpo

wderaddition

todiet,for

35days

Malealbino

rats,1

mon

th,140-150

g

AflatoxinsB1andG1

850ng/kgb.w./d

ayfor35

days

Weightgain,foodintake

↓Blood

:HGB,R

BC,P

LT↓,HCT,W

BC↑

Serum:Fe,T-A

OC,cho

lesterol↓,TG,LDL-c,HDL-c,

ALT

,AST

,ALP

,MDA↑

Liver:SO

D,C

AT↓,MDA↑

AFB

1

Weightgain

(++),food

intake

(+++)

Blood

:PLT

,HCT,W

BC,H

GB(++),RBC(+++)

Serum:M

DA(+),LD

L-c,HDL-c,Fe,cho

lesterol,T

-

AOC,T

G,A

LT,A

ST,A

LP(++)

Liver:SO

D,M

DA(++),CAT(+++)

AFG

1

Weightgain

(++),food

intake

(+++)

Blood

:PLT

,HCT,W

BC,H

GB(++),RBC(+++)

Serum:L

DL-c,HDL-c,Fe,cho

lesterol,T

G,A

LT,

AST

,ALP

,MDA(++),T-A

OC(+++)

Liver:SO

D,M

DA(++),CAT(+++)

Non

e

Xuetal.[79]

Polysaccharides

from

Morinda

officina

lisprocessed

root

(processed

root

byBeijin

gSanh

ePharm

aceuticalC

o.,L

td.)

500mg/kg

i.g.,on

ceadayfor18

days

FemaleBalb/cmice

Con

canavalin

A-ind

uced

liver

damage10

mg/kg

i.v.,

once

aweek

Weightindex:liver

andkidn

ey↑,thym

us↓

Serum:A

LTandAST

↑Liver:CAT↓,MDA↑

Weightindex:kidn

ey(0),liver

(+),

thym

us(+++)

Serum:A

LTandAST

(+++)

Liver:CAT,M

DA(+)

Not

stud

ied

12 Oxidative Medicine and Cellular Longevity

Table3:Con

tinu

ed.

Reference

Plant

preparation,

dose,w

ayandtimeof

treatm

ent,

andanim

als

The

toxicsubstance,do

se,w

ayandtime

ofexpo

sure,and

negative

effects

Protectiveeffectsof

plantpreparation

Effectsof

plantperse

Ahm

edetal.[86]

Pulicaria

petiolarisaerialpart

methano

lextract

Pretreatm

ent50

or100mg/kg,p

.o.,

for5days

MaleSw

issalbino

mice,25-27g

LPS-indu

cedhepato-andcardiotoxicity,a

singledo

se10

mg/kg

i.p.

Serum:A

LT,A

ST,A

LP,L

DH,C

K-M

B,cTnI

↑Liver:GSH

,SOD↓,MDA,N

F-κB

,TNF-α,IL-6,

averageseverity

ofhistop

atho

logical

lesion

s↑

Heart:G

SH,SOD

↓,MDA,N

F-κB

,TNF-α,IL-6,averageseverity

ofhistop

atho

logical

lesion

s↑

Serum:A

LT,A

ST,A

LP,C

K-M

B,cTnI

(++both

doses),L

DH

(++50,+

++100)

Liver:averageseverity

ofhistop

atho

logical

lesion

s(+

50,+

+100),N

F-κB

,(++both

doses),

MDA,IL-6,TNF-α,G

SH(++50,+

++100),

SOD

(+++both

doses)

Heart:IL-6,NF-κB

,TNF-α,G

SH,SOD

(++both

doses),average

severity

ofhistop

atho

logicallesions

and

MDA(++50,+

++100)

100mg/kg

onlystud

ied:

Serum:

LDH

↓

Raish

etal.[87]

Lepidium

sativum

seed

ethano

lextract

Pretreatm

ent150and300mg/kg

p.o.,for

14days

MaleWistarrats,2-m

onth-old,180-205

g

D-G

alactosamine+LP

S-indu

cedhepatotoxicity

400mg/kg

and30

μg/kg,respectively,i.p.,on

the15

th

day

Serum:A

LT,A

LP,A

ST,bilirubin,

GGT↑

Liver:CAT,G

SH,SOD↓,MDA,M

PO,N

F-κB

9(p65)

DNAbind

ingactivity,m

RNAexpression

ofTNF-α,

IL-6,IL-10,

HO-1,iNOS↑

Serum:A

LT,A

LP,A

ST,G

GT(++both

doses),

bilirub

in(++150,+++300)

Liver:CAT(+

150,++300),G

SH,SOD,M

DA,

MPO,N

F-κB

9(p65)

DNAbind

ingactivity,m

RNA

expression

ofTNF-α,IL-6,HO-1,iNOS

(++both

doses)

Liver:expression

ofIL-10(+

150,↑300)

The

greaterthedo

sethemoredistincttheeffect

Not

stud

ied

Albrahim

and

Binobead[30]

Moringa

oleifera

leaf

water

extract

200mg/kg

b.w.,i.g.,for4weeks

Malealbino

rats,9-10weeks,110-130

g

Mon

osod

ium

glutam

ate-indu

cedhepatotoxicity,

5mg/kg

b.w.,i.g.,for4weeks

Serum:T

P,globu

lins↓,ALT

,AST

↑Liver:CAT,SOD,G

ST,G

SH↓,MDA,D

NAdamage,

expression

ofPCNAand

P53

proteins

↑

Serum:globu

lins(+),TP(++),ALT

,AST

(+++)

Liver:CAT,SOD,G

ST,G

SH,M

DA(++);DNA

damage(++),expression

ofPCNAandP53

proteins

(++)

Non

e

↓:adecrease

vs.con

trol;↑:anincrease

vs.con

trol;(+):aslight

beneficialeffect;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect;(0):no

beneficialeffect.

13Oxidative Medicine and Cellular Longevity

Table4:The

protective

effectsof

plantpreparations

againstcarcinogens.

Reference

Plant

preparation,

dose,w

ayandtimeof

treatm

ent,

andanim

als

The

carcinogen,d

ose,way

andtimeof

expo

sure,

andnegative

effects

Protectiveeffectsof

plantpreparation

Effectsof

plantperse

Bingületal.

[89]

Vaccinium

corymbosum

L.blueberriesho

mogenate

addedto

diet8%

(w/w

)and

givento

ratsfor16

weeks

MaleWistarrats,200-250

g

Diethylnitrosam

ine200mg/kg,i.p.,at

4th,

6thand8thweekof

theexperiment

Serum:A

LT,A

ST,L

DH

↑Liver:MDA,D

C,P

C,G

SH,G

ST↑,SO

D,

CAT,G

Px↓

Liver:relative

mRNAexpression

of

SOD,C

AT,G

Px↓,of

GST

-pi↑

Serum:A

LT(++),AST

(+++),LD

H(↓)

Liver:GPx,GSH

,GST

,SOD,C

AT(+),PC(++),

MDA(+++),DC(↓)

Liver:relative

mRNAexpression

ofSO

D,C

AT,

GPx(0),of

GST

-pi(++)

Non

e

Khanetal.

[88]

Phoenixdactylifera

L.(A

iwadates)water

extract

0.5or

1.0g/kg

b.w.,daily

for10

weeks,startingon

the

next

dayafterdiethylnitrosamine

MaleWistarrats,5-6-w

eek-old,

100-120g

Diethylnitrosam

ine-indu

cedhepatocellu

lar

carcinom

a,twodo

ses

180mg/kg

b.w.at15

days

interval,p

.o.

Serum:A

LT,A

ST,A

LP,IL-1α

,IL-1β

,GM-C

SF,

MDA↑,SO

D,G

R,G

Px,CAT,IL-2,IL-12,IL-4

↓

0.5g/kg

b.w.:

Serum:C

AT,M

DA,IL-1β

(-),IL-4

(0),IL-2

(+),

SOD,G

R,G

M-C

SF,A

LP(++),ALT

,AST

,GPx,IL-1α,IL-12

(+++)

1.0g/kg

b.w.:

Serum:IL-4,CAT(0),ALP

,MDA,

AST

,IL-1α

(↓),

SOD,G

R,IL-β,G

M-C

SF,IL-2(++),

ALT

(+++),GPx,IL-12(↑)

Not

stud

ied

Cho

ietal.

[46]

Centella

asiatica

leaf

(MartinBauer

GmbH

&Co.KG,V

estenb

ergsgreuth,

Germany)

75%

ethano

lextract

100or

200mg/kg,p

.o.,daily

for5days

followingcarcinogen

MaleSprague-Daw

leyrats,6-w

eek-old,

180-200g

Dim

ethylnitrosamine-indu

cedliver

injury

30mg/kg,i.p.

Serum:A

ST,A

LT,A

LP,totalbilirub

in,T

NF-α,IL-1β

,IL-6,

INF-γ,IL-10,IL-12,IL-2,G

M-C

SF↑

Liver:fibrosis,intralobu

lardegeneration

,focalnecrosis,

MDA↑,GPx,SO

D,C

AT↓

Serum:A

ST,INF-γ(↓

both

doses),IL-10

(++100,0200),IL-12

(++100,+200),total

bilirub

in,A

LT(+

100,++200),

ALP

(++100,+++200),

IL-12(+++100,++200),T

NF-α,IL-1β

,IL-6,

GM-C

SF(+++both

doses)

Liver:SO

D,C

ATandfibrosis(+

100,++200),

GPx(++100,+++200),intralobu

lar

degeneration

andfocaln

ecrosis(++both

doses),

MDA(+++100,↓200)

Not

stud

ied

Kiziltas

etal.

[47]

Ferulago

angulata

flow

ers80%

methano

lextract

150or

300mg/kg

b.w.,p.o.,d

aily,for

21days

MaleWistarrats,4-w

eek-old,

abou

t200g

N-N

itrosodimethylamine(dim

ethylnitrosamine)-ind

uced

oxidativestress,10mg/kg

b.w.,i.p.,forthefirst7days

Liver:SO

D,G

Px,CAT↓

Liver:SO

D(+

150,++300),

GPx,CAT(++both

doses)

Bothdo

ses:

Liver:CAT

↓

Rou

hollahi

etal.[90]

Curcumapu

rpurascens

BI.rhizom

edichloromethane

extract

250or

500mg/kg,p

.o.,on

ceadayfor

2mon

ths,afterazoxym

ethane

MaleSprague-Daw

leyrats,6

weeks,200–220

g

Azoxymethane-ind

uced

aberrant

cryptfoci

15mg/kg,s.c.,on

ceaweekfor2consecutiveweeks

Colon

:CAT,G

Px,SO

D↓,aberrant

cryptfoci

form

ationandMDA↑

Colon

:aberrantcryptfociform

ation,

MDA,C

AT(++both

doses),

GPxandSO

D(++250,+++500)

Not

stud

ied

↓:adecrease

vs.con

trol;↑:anincrease

vs.con

trol;(+):aslight

beneficialeffect;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect;(0):no

beneficialeffect;(-):intensification

oftheharm

fuleffect.

14 Oxidative Medicine and Cellular Longevity

deterioration of antioxidant barrier, observed in animalsexposed to ethanol [44, 56, 91]. The involvement of oxidantstress into ethanol toxicity was also showed by Phunchagoet al. [92] who observed the protective influence of antioxi-dant vitamin C. The studies presented in the current reviewproved that plant materials showed a wide range of protectiveactions including ameliorating of liver markers, oxidativeparameters, and alleviation of histopathological changes[56, 91, 92]. The involvement of LPS-TRL4-NF-κB pathwaywas also been proved [56, 65].

The detailed results of the performed studies are pre-sented in Table 5.

2.6. The Protective Influence of Plant Preparations againstToxic Effects of Antipyretic and Analgesic Drugs. The applica-tion of antipyretic and analgesic drugs has been growing rap-idly in recent years. Acetaminophen, known also asparacetamol, N-acetyl-p-aminophenol or APAP, a substituteof aspirin, is one of the most often used over-the-countermedicines. However, its application can cause severe hepato-toxicity, and this fact is all the more dangerous because ofpossible overdose resulting from self-administration [18, 22,40, 95]. Another side effect, connected with paracetamolapplication, is nephrotoxicity [22, 40]. The harmful actionof acetaminophen includes oxidative stress, particularly thedepletion of GSH and protein sulfhydryl groups blocking[96]. Several studies revealed the possibility of plant extractapplication as protective adjuvants, wherein Moringaperegrine, Genista quadriflora, Teucrium polium geyrii, andCassia surattensis showed the best influence which includednot only amelioration of liver damage markers but alsoimprovement of antioxidant parameters and reduction ofthe lipid peroxidation process [19, 20, 96].

The details concerning the mentioned investigations arepresented in Table 6.

2.7. The Protective Influence of Plant Preparations againstToxic Effects of Antibiotics. Not only are antibiotics used forthe treatment of Gram-negative bacterial infection, but theyalso can cause side effects to occur [98, 99]. Gentamycinbelongs to those which are used in case of strains resistantto other antibiotics, but its application can lead to hepatoand nephrotoxicity [28]. The similar properties are shownby an antibiotic polymyxin, whose application was ceasedbecause of its nephrotoxicity, but an increased drug resis-tance of Gram-negative strains has rendered it being usedagain [99]. Oxidative stress as well as inflammation processeswas suggested to take part in the development of the men-tioned negative effects [29, 98, 99]. Materials obtained fromplants containing antioxidant components and affectingimmune functions were investigated as to their possible pro-tecting application, and the results seem to be promisingalthough they also pointed to the necessity of taking properprecautions and precise choosing the dose as in some casesthe higher dose showed a better influence [29, 98], whileother authors reported quite opposite results [28].

The details concerning the above mentioned issues arepresented in Table 7.

2.8. The Protective Influence of Plant Preparations againstToxic Effects of Anticancer Drugs. Cancer successful therapyis often a great problem because of the side effects of theapplied agents which include deterioration of reproductiveproficiency [23], nephrotoxicity [16, 100], and hepatotoxicity[37] and cardiotoxicity [26]. The results of the studies pre-sented below clearly show that the toxic action of anticancerdrugs is strongly connected with the prooxidative processes,deterioration of antioxidant barrier, and histopathologicalchanges. The extracts of different plants, used as spices anddrugs in traditional medicine for centuries, were studied fortheir protective potential [101]. Both simple extracts and par-ticular fractions [25, 26] proved their protective propertieswhich included the amelioration of the disturbed oxidantparameters. Antioxidant and antiapoptotic properties ofplant extracts were confirmed by in vitro investigationsperformed on renal tubular epithelia cells [100] and cardio-myocytes [25]. Histopathological changes were also foundto be relieved by plant materials [16, 23, 24, 26, 102].

The details concerning the above mentioned issues arepresented in Table 8.

2.9. The Protective Influence of Plant Preparations againstSide Effects of Various Drugs. Many drugs’ administration isaccompanied with numerous side effects which cause lifecomplication and may negatively influence patients’ compli-ance. These facts prompted the searching for any adjuvantsreversing or at least alleviating side effects. Recently, a grow-ing interest in plant origin substances, often those used in tra-ditional medicine, is being observed [104, 105]. The studiespresented below revealed the effectiveness of plant extractsagainst toxicity of diverse drugs: psychiatric (lithium carbon-ate), thyrostatic (Propylthiouracil), and cardiac activity stim-ulators (Isoproterenol), a contrast medium (Iodixanol), anddermatological medicine (Triamcinolone acetonide). Thenegative influence of the studied drugs often included deteri-oration of antioxidant barrier [105, 106]. The studiedpreparations showed beneficial effects, and in vitro studiesconfirmed their antioxidant potential [104, 107].

The details concerning the above mentioned issues arepresented in Table 9.

2.10. The Protective Effects of Plant Preparations Observed inAnimal Models of Different Disorders

2.10.1. The Protective Effects of Plant Preparations Observedin Arthritis. Arthritis has recently become a serious, world-wide problem as this disease is related with pain and physicaldisability, and no effective therapy except for a surgery can beapplied [49]. As the risk of it increases with age, the growingspam life contributes to the still enhancing incidence. Plantsubstances were found to prevent enhancement of the proin-flammatory cytokines like IL-1β, IL-6, and TNF-α, involvedinto osteoarthritis pathogenesis of OA. Additionally, thereduction of metalloproteinases responsible for joint damageas well as upregulation of their inhibitors—TIMPs and extra-cellular matrix components—was observed [48, 49]. Further-more, plant origin substances were reported to reverse

15Oxidative Medicine and Cellular Longevity

oxidative parameters’ disturbances, also taking part in osteo-arthritis development [55].

The detailed outcomes of the performed studies are col-lected in Table 10.

2.10.2. The Protective Effects of Plant Origin Materials inCases of Neurodegenerative Disorders. The next type of dis-orders studied with using an animal model was neurode-generative diseases. ROS have been reported to beinvolved in the development of Alzheimer’s, Huntington’s,and Parkinson’s diseases. Extracts obtained from plantsused in traditional Chinese and Ayurveda medicine, posses-sing numerous therapeutic properties and containing anti-oxidant components, were shown to exert a considerablebeneficial influence [31, 32, 39].

Traumatic brain injury, regarded as a worldwide gravechallenge being a cause of many death and disability cases,is considered to need an effective therapy. Water extractsof plant commercial products were revealed to show abeneficial influence on immunological and oxidativeparameters [38, 60].

Psychiatric disorders like anxiety or depression were alsoproved to be connected with neurodegenerative disturbancesas well as changes of immunological and oxidative parame-ters which were alleviated by plant extracts [111, 112].

The detailed outcomes of the performed studies are col-lected in Table 11.

2.10.3. The Protective Effects of Plant Origin Materials inCases of Animal Menopause Model. In menopausal women,the deficiency of sex hormones can lead to various distur-bances of organism. The research concerning hormonereplacement therapy showed that it can cause different sideeffects, so the attention was paid to nonpharmaceuticalagents, all the more because plant flavonoids were provedto possess phytoestrogen properties [114]. In the performedstudies, plant origin materials improved some elements oflipid profile and oxidative parameters deteriorated by ovari-ectomy [115]. Bone mineral density in rats was also amelio-rated, although this effect became less distinct along withlengthening of the experiment [114]. However, in some cases,the obtained results were not so distinctly beneficial [116].

The details of the performed studies are collected inTable 12.

2.10.4. The Protective Effects of Plant Origin Materials inLung Disorders. Plant origin substances were shown to pos-sess some efficacy against lung disorders, and the beneficialeffect included the improvement of oxidative and inflamma-tory parameters, morphological disturbances, and factorscontrolling extracellular matrix functions and vascularhomeostasis [117–119].

The details of the performed studies are collected inTable 13.

2.10.5. The Protective Effects of Plant Origin Materials inLipid Profile Disturbances. Lipid profile disturbance is associ-ated with severe diseases like diabetes as well as hepatic andcardiovascular disorders [120]. It is rated among the mainfactors causing disability and death [34]. Factors which were

used to induce such a condition were also found to causeintensification of prooxidative processes connected withdeterioration of antioxidant defence and DNA damage. Plantpreparations proved to display beneficial effects, althoughonly in one case per se influence was studied [120].

The detailed results of the performed studies are collectedin Table 14.

2.10.6. The Protective Effects of Plant Origin Materials inIschaemia/Reperfusion Model. Ischaemia/reperfusion dam-age is a serious problem which can occur as a consequenceof surgery, e.g., transplantation or coronary bypass, andmay lead to severe injuries, resulting among other thingsfrom increase in ROS generation. Pretreatment with plantmaterials, obtained from species used in traditional medicine,was found to be effective against prooxidative processes andhistopathological changes observed in ischaemia/reperfusionanimal model [123–126].

The detailed results of the performed studies are collectedin Table 15.

2.10.7. The Protective Effects of Plant Origin Materials inAnimal Model Diabetes. Plant origin substances wereobserved to be effective at reversing disturbances observedin the course of diabetes. A wide range of agents was studied,simple extracts, combinations of two extracts as well as an oil,banana pasta or substances separated from plant material. Agreat variety of species was investigated, including herbs,fruits, or vegetables. Many of them had been known as beinguseful in different fields of medicine, sometimes from ancienttimes [66, 127–129]. In several studies, biochemical, oxidant,and inflammatory parameters in the blood and organsincluding the lens, brain, liver, pancreas, kidney, and heartwere found considerably improved or restored by differentmaterials [42, 57, 66, 128, 129]. Histopathological investiga-tion revealed that plant preparations showed a considerableability to attenuate pancreas, kidney, and liver damageobserved in the animal model of diabetes [127, 128, 130].The beneficial influence of plant extracts on the deteriorationof sperm quality [131], diabetes-associated cataract, and ret-inopathy and an ability to suppress MAPK signal transduc-tion [42] and the amyloidogenic pathway [57] werereported. However, there are limitations of these investiga-tions as in most of them the effect of the applied plant sub-stance was not studied.

The detailed results of the performed studies are collectedin Table 16.

2.10.8. The Protective Effects of Plant Origin Materials inAnimal Model of Obesity. Plant origin preparations were alsoinvestigated as to their potential to prevent pathological pro-cesses connected with obesity. This direction seems to be ofgreat importance as obesity and related disturbances, result-ing from sedentary lifestyle as well as excessive consumption,are becoming more and more serious world problem [132,133]. Diet-induced obesity was found to be connected withdifferent disturbances of various parameters including livermarkers and lipid profile as well as inflammation, lipogene-sis, and oxidative balance. The performed research revealed

16 Oxidative Medicine and Cellular Longevity

Table5:The

protective

effectsof

plantorigin

substances

againsttoxicity

ofethano

l.

Reference

Plant

preparation,

dose,w

ayandtimeof

treatm

ent,and

anim

als

The

dose,w

ayandtimeof

expo

sure,and

negative

effects

Protectiveeffectsof

plantpreparation

Effects

ofplant

perse

Akbari

etal.[93]

Zingiberoffi

cina

leRoscoe(ginger)rhizom

ehydroalcoh

olicextract

1g/kg

ofb.w./d

,p.o.,for28

days

Sprague-Daw

leymalerats,about

220g

Ethanol4g/kg

ofb.w./d

,p.o.,for28

days

Serum:T

,SHBG,D

HEAs↓

Testes:weight,Zn,

Mg,Fe,C

u↓;SO

D,

GPx,CAT↓,MDA,tHcy

↑

Serum:T

(++),SH

BG,D

HEAs(+++)

Testes:Zn(-),Cu(+),Mg,weight,SO

D,G

Px,

CAT,M

DA,tHcy

(+++),

Fe(↑)

Serum:

T↓

Testes:

Fe↑,Zn,

Mg,Cu

↓

Phu

nchago

etal.[92]

Tiliacoratriand

raaerialpartsaqueou

sextract,

100,200or

400mg/kg

b.w.,p.o.,for

14days

after

developing

ethano

ldependenceby15-w

eek

alcoho

ltreatment

MaleWistarrats,8

weeks

Ethanol-dependencecaused

byagradual

increase

ofethano

lcon

tent

indrinking

fluidfrom

5%up

to30%,a

15-w

eek

alcoho

ltreatment

Hippo

campu

s:AChE

,MDA↑,SO

D,

CAT,G

Px↓,neuron

densityin

subregions

CA1,CA2,CA3

anddentategyrus↓

Hippo

campu

s:AChE

(+100,++200,0400),

CAT(+++100and200,++400),G

Px

(↑100and200,+++400),M

DA,SOD(++alld

oses),

neuron

densityin

subregions

CA1,CA2,

andCA3anddentategyrus

(++alld

oses)

Not

stud

ied

Liuetal.[91]

Ginseng

oligop

eptidesextractedfrom

rootsof

Pana

xginseng

C.A.M

eyer

(JilinTaigu

BiologicalE

ngineering

Co.,

Ltd.,C

hina)

Pretreatm

ent:0.0625,0.125,0.25,and0.5g/kg

b.w.,for30

days,p

.o.,

Sprague-Daw

leymalerats,180-220

g

One

dose

of50%

ethano

l7g(17.5mL)/kgb.w.,i.g.

Serum:A

LT,A

ST,T

G,A

LP,T

NF-α,IL-

6,IL-1βandLP

S↑,TC,H

DL-c,LD

L-c,

TP↓

Liver:steatosisandMDA↑,SO

D,G

SH,

GPx↓

Serum:A

LP(-lower

doses,0thehigheston

e);

LDL-c,TP(0

alld

oses),HDL-c(0

thelowestdo

se,

+otheron

es),TC(++alld

oses),TG(++lower

doses,

+++higher

ones),LP

S(+++except

for0.25

mg/kg

++),

ALT

,AST

,(+++alld

oses),TNF-α,IL-6

andIL-1β(↓

alld

oses)

Liver:steatosis(++alld

oses),GPx(+

lower

doses,+++

0.25,↑

0.5),G

SH(+

lower

doses,+++higher

ones),

MDA(+++alld

oses),SO

D(+

lower

doses,++higheston

e)

Not

stud

ied

Jung

etal.[94]

Glycyrrhiza

uralensisFisher

root

70%

ethano

lextract

100mg/kg

b.w.,p.o.,for

4weeks

MaleC57BL/6mice

Dietary

ethano

lLieber–D

eCarliliq

uiddiet—36%

ofenergy

from

ethano

l,for4weeks

Serum:T

NF-α,A

LT,A

ST↑

Liver:GSH

↓,TGandmRNAexpression

ofSrebf1,C

d36,Lp

l,Fatp4↑

Serum:T

NF-α,A

LT,A

ST(++)

Liver:TG,m

RNAexpression

ofSrebf1,C

d36

andLp

I(++),GSH

andmRNAexpression

ofFatp4(+++)

Not

stud

ied

Louetal.[65]

Lind

erae

radix(preparedslices,Z

hejiang

Tiantaishan

Wuyao

BiologicalE

ngineering

Co.,L

td.,China)extractedfrom

tubers

ofLind

eraaggregata(Sim

s)Kostern,75%

ethano

lextract

1,2or

4g/kg,i.g.,for20

days

MaleSprague-Daw

leyrats,160–180

g

50%

alcoho

l10

mL/kg

b.w.,on

ceadayfor20

days,

i.g.

Serum:A

LT,totalbilirub

in,IL-6,IL-8,

TNF-α,N

F-κB

↑Portalvein:

LPS↑

Smallintestine:expressionof

tight

junction

proteins

claudin-1and

occlud

in↓

Serum:IL-6(+

1and2,+++4),T

NF-α

(+++1,++2,04),N

F-κB

(++1,+++2,and4),

ALT

,totalbilirub

in,IL-8(+++alld

oses)

Portalvein:

LPS(+++alld

oses)

Smallintestine:expressionof

tightjunction

proteins

claudin-1(+

alld

oses)andocclud

in(+++1,++2,04)

Not

stud

ied

17Oxidative Medicine and Cellular Longevity

Table5:Con

tinu

ed.

Reference

Plant

preparation,

dose,w

ayandtimeof

treatm

ent,and

anim

als

The

dose,w

ayandtimeof

expo

sure,and

negative

effects

Protectiveeffectsof

plantpreparation

Effects

ofplant

perse

Tang

etal.[56]

Cynarascolym

usL.

(articho

ke)in

freeze-dried

powder

(HuimeiAgriculturalScience

andTechn

ology

Co.,L

td.,China)

Pretreatm

ent,1ho

urbefore

alcoho

l0.4,0.8or

1.6g/kg

b.w.,p.o.,d

ailyfor10

days

MaleInstituteof

CancerResearch,

mice,

7-week-oldabou

t25

g

Ethanol

12mL/kg

b.w.,p.o.,

daily

for10

days

Liverindex:↑

Serum:A

LT,A

ST,T

G,T

C↑

Liver:SO

D,G

SH↓,MDA↑,expression

levelofT

LR4andNF-κB

p50↑,scoreof

steatosis,inflam

mationandnecrosis↑

Liverindex:(++alld

oses)

Serum:A

LT(0

0.4,+0.8,+++1.6),TG(0

0.4,++0.8

and1.6),A

ST(+

0.4and0.8,++1.6),

TC(+

0.4,++0.8and1.6)

Liver:SO

D,G

SH(++0.4and0.8,+++1.6),M

DA(+

0.4,+++0.8,and1.6),score

ofsteatosis(+

0.4,++0.8,

and1.6),score

ofinflam

mation(+

0.4,++0.8,and1.6),

scoreof

necrosis(++alld

oses),expression

ofTLR

4(+

0.4,++0.8,+++1.6),expressionof

NF-κB

p50

(++0.4,+++0.8and1.6)

Not

stud

ied

Dogan

and

Anu

k[44]

Platan

usorientalisL.

leas

water

extract

20or

60mg/mLleafinfusion

adlibitum

,for

28days

MaleWistarrats,2

mon

thsaged,about

200g

20%ethano

lwaterad

libitum

for28

days

Serum:A

ST,A

LT,LDH,G

GT,U

A,urea

↑,cholesterol,HDL-c↓

Liver:GSH

↓,GST

,MDA↑

Erythrocytes:GST

,MDA↑

Kidney:MDA↑,SO

D,G

Px,CAT↓

Serum:G

GT(-20,++60),ALT

,urea(+

20,0

60),HDL-

c(+

both

doses),LDH(++20,+

++60),cholesterol(++

20,+

60),AST

,UA(+++both

doses)

Liver:GSH

andGST

(+both

doses),

MDA(++both

doses)

Erythrocytes:GST

(0both

doses),

MDA(++20,+

++60)

Kidney:SO

D(-20,+

60),CAT(-20,+

+60),

MDA(+++both

doses),G

Px(+++20,↑

60)

Not

stud

ied

↓:adecrease

vs.con

trol;↑:anincrease

vs.con

trol;(+):aslight

beneficialeffect;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect;(0):no

beneficialeffect;(-):intensification

oftheharm

fuleffect.

18 Oxidative Medicine and Cellular Longevity

Table6:The

protective

effectsof

plantsubstances

againsttoxicity

ofantipyreticandanalgesicdrugs.

Reference

Plant

preparation,

dose,w

ayandtimeof

treatm

ent,andanim

als

The

nameof

drug,d

ose,way

andtimeof

expo

sure,and

negative

effects

Protectiveeffectsof

plantpreparation

Effectsof

plant

perse

Bou

zenn

aetal.[21]

Pinu

shalepensisL.

needlesessentialo

ilPretreatm

ent,1%

(w/w

),withado

seof

1mL/kg,p

.o.,for56

days

FemaleWistarrats,150-200

g

Aspirin-ind

uced

liver

and

kidn

eydamage

600mg/kg

thrice

adayfor4days,p

.o.

Weight:body,liver,kidney↓

Serum:glucose,T

C,A

ST,A

LT,LDH,C

R,urea

↑Liver:TBARS↑,SO

D,C

AT,G

Px↓

Kidney:TBARS↑,SO

D,C

AT,G

Px↓

Weight:body,liver,kidney(+++)

Serum:glucose,T

C,A

ST,A

LT,L

DH,C

R,

urea

(+++)

Liver:TBARS,SO

D,C

AT,G

Px(+++)

Kidney:TBARS,SO

D,C

AT,G

Px(+++)

Non

e

Ahm

adand

Zeb

[18]

Trifoliu

mrepens

leaf

water

extract

11mgof

solid

weight/mL;

1,2,

or3mLof

extractperdayfor2weeks

Malealbino

miceabou

t28.6g

Acetaminop

hen-indu

cedhepatotoxicity

300mg/kg

for2weeks

Serum:T

C,T

G,L

DL-c,ALT

,AST

,ALP

,glucose↑,HDL-c↓

Blood

:RBC,H

GB,H

CT,P

LT↓,

WBC↑

Liver:TBARS↑,GSH

↓

1mL:

Serum:A

LP,glucose

(0),TC,T

G(+),HDL-c,ALT

,AST

(++),LD

L-c(+++)

Blood

:PLT

(0),HCT(+),WBC(++),RBC,H

GB(+++)

Liver:GSH

(+),TBARS(++)

2mL:

Serum:T

C(+),ALT

,AST

,ALP

,TG,H

DL-c,

glucose(++),LD

L-cholesterol(+++)

Blood

:PLT

(+),RBC,H

GB,H

CT,W

BC(+++)

Liver:GSH

,TBARS(++)

3mL:

Serum:H

DL-c(0),TC,A

ST,A

LT,A

ST(++),

glucose,LD

L-c(+++)

Blood

:PLT

,RBC,H

GB,H

CT,W

BC(+++)

Liver:TBARS,GSH

(++)

Stud

iedon

lyfor

the1mLdo

seSerum:T

C↓,

HDL-c↑

Azim

etal.[19]

Moringa

peregrinaleaves

70%

ethano

lextract

200mg/kg

b.w.p

.o.,on

eho

urpriorto

acetam

inop

hen,

for4weeks

Femalealbino

rats,about

160g

Acetaminop

hen-indu

cedhepatotoxicity

750mg/kg

b.w.,p.o.

Serum:A

LT,A

ST,A

LP,G

GT↑

Blood

:GSH

,CAT,SOD↓,MDA↑

Liver:GSH

,CAT,SOD

↓,GPx,MDA↑

Brain:G

SH,SOD↓,GPxandMDA↑

Serum:A

LT,A

LP(++),AST

,GGT(+++)

Blood

:GSH

,CAT,SOD,M

DA(+++)

Liver:GSH

,CAT,SOD,G

Px,MDA(+++)

Brain:G

Px,MDA(++),GSH

,SOD(+++)

Not

stud

ied

Mishra

etal.[97]

Pand

anus

odoratissimus

root

ethano

licextract

200or

400mg/kg

b.w.,p.o.,onceadayfor7

days

Wistarrats180-200g

Paracetam

ol-ind

uced

hepatotoxicity

2g/kg

b.w.,p.o.,onthe5thday

Serum:A

ST,A

LT,A

LP,d

irectbilirub

in,total

bilirub

in,T

G↑

Serum:A

LT,A

ST,A

LP,d

irectbilirub

in,

totalb

ilirubin,

TG(++);

The

protective

effectwas

better

for

thehigher

dose.

Not

stud

ied

Rashid

etal.[40]

FagoniaolivieriDC.aerialp

arts

95%

methano

licextract

200and400mg/kg,i.g.,for7days

MaleSprague-Daw

leyrats,

6-week-old,

180-200g

Acetaminop

hen-indu

cedtoxicity

750mg/kg

for7days,i.g.

Serum:A

ST,A

LT,A

LP,L

DH,totalbilirub

in,

cholesterol,TG,H

DL,

LDL↑

Blood

:HGB,W

BC↓,PLT

↑Liver:weight,CAT,SOD,G

Px,GR,G

SHand

TP↓,DNAfragmentation

andTBARS↑

Serum:A

ST,A

LT,L

DH,L

DL(++)both

doses,

ALP

,totalbilirub

in,T

G,H

DL(++200,+++400),

cholesterol(+++200,400↓)

Blood

:HGB(++both

doses),W

BC(+++both

doses),

PLT

(+++200,↑400)

Liver:TP(0

200,++400),

DNAfragmentation

,SOD,G

R,G

SH,T

BARS(++both

doses),w

eight,CAT,

GPx(++200,+++400)

400mg/kg

stud

iedon

lySerum:T

G,

HDL,

cholesterol↓

Blood

:WBC↑,

HGB↓

Liver:TBARS↓

19Oxidative Medicine and Cellular Longevity

Table6:Con

tinu

ed.

Reference

Plant

preparation,

dose,w

ayandtimeof

treatm

ent,andanim

als

The

nameof

drug,d

ose,way

andtimeof

expo

sure,and

negative

effects

Protectiveeffectsof

plantpreparation

Effectsof

plant

perse

Ebada

[95]

Chamom

illarecutita

L.(chamom

ile)and

Cum

inum

cyminum

L.(green

cumin)

essentialo

ils(H

ashem

BrothersforEssentialOils

and

Aromaticprod

ucts)

Pretreatm

entp.o.,for

14days,

400mg/kg/day

(cum

in),250mg/kg/day

(chamom

ile)

MaleWistarrats,180-200

g

Acetaminop

hen-indu

cedhepatotoxicity

1g/kg

p.o.,a

singledo

seon

the14

thday

Serum:A

LTandAST

↑Liver:GSH

↓,MDAandSO

D↑

Liverhistop

atho

logy:h

epatocytenecrosis,

inflam

mation,

degeneration

,dilated

centralvein,

hemorrhage↑

Cum

inessentialo

il:Serum:A

LTandAST

(+++)

Liver:GSH

(0),MDA(-)andSO

D(0)

Liverhistop

atho

logy:hepatocytenecrosis,infl

ammation,

degeneration

,dilated

centralvein,

hemorrhage(++)

Chamom

ileessentialo

il:Serum:A

LT(++)andAST

(0)

Liver:MDA(-),GSH

,SOD(++)

Liverhistop

atho

logy:h

epatocytenecrosis,h

emorrhage

inflam

mation,

dilatedcentralvein,

degeneration

(+)

Not

stud

ied

Baalietal.[20]

Rich-po

lyph

enol

(n-butanol)fraction

sof

80%

methano

licextractof

Genista

quadriflora

Mun

byand70%

methano

licextractof

Teucrium

poliu

mgeyriiMaire

Pretreatm

ent

300mg/kg

daily,p

.o.,for10

days

MaleWistarrats,about

142g

Acetaminop

hen-indu

cedhepatotoxicity

Asingledo

seof

1g/kg,p

.o.

Plasm

a:AST

,ALT

↑Liver:SO

D,G

Px,GR,G

SH,G

ST↓,CYP2E

1,TBARSandmRNAof

TNF-αexpression

↑Livermitocho

ndria:CSandrespiratorychain

complexes

IandII↓

Genista

quadriflora

Plasm

a:AST

,ALT

(+++)

Liver:SO

D,G

Px,GSH

,GST

,TBARS,CYP2E

1and

mRNAof

TNF-αexpression

(+++),GR↑

Livermitocho

ndria:CSandrespiratory

chaincomplex

I(+++),respiratory

chaincomplex

II↑

Teucrium

poliu

mgeyrii

Plasm

a:AST

,ALT

(+++)

Liver:SO

D,G

Px,GSH

,GST

,TBARS,CYP2E

1and

mRNAof

TNF-αexpression

(+++),GR↑

Livermitocho

ndria:CS(+++),respiratory

chaincomplexes

IandII↑

Not

stud

ied

UthayaKum

aretal.[96]

Cassiasurattensisseed

methano

lextract

Pretreatm

ent250or

500mg/kg

b.w.,p.o.,

once

daily

for7days

MaleSw

issalbino

mice,6-8-week-old,

25-

30g

Paracetam

ol-ind

uced

hepatotoxicity

Asingledo

seof

1g/kg

b.w.,p.o.

Relativeliver

weight:↑

Serum:A

LT,A

ST,A

LP↑

Liver:GSH

,SOD↓,MDA↑

Relativeliver

weight:(+++both

doses)

Serum:A

LT,A

ST,A

LP(++both

doses)

Liver:MDAandGSH

(++250,+++500),

SOD(++250,↑500)

Not

stud

ied

Chinn

appan

etal.[22]

Eurycomalongifo

liaroot

water

extract

Physta®

(Biotrop

icsMalaysia)

100,200or

400mg/kg,p

.o.,1ho

urbefore

paracetamol,

for14

days

MaleWistarrats,12-week-old,

120-150g

Paracetam

ol-ind

uced

neph

rotoxicity

200mg/kg

daily

for14

days,i.p.

Serum:T

P,A

LB↓,creatinine

↑Blood

:urea↑

Creatinineclearance:↓

100mg/kg:

Serum:A

LB,creatinine(0),TP(+)

Blood

:ureaand(0)

Creatinineclearance:(0)

200and400mg/kg:

Serum:T

P,A

LB,creatinine(+++)

Blood

:urea(+++)

Creatinineclearance:(+++)

Not

stud

ied

↓:adecrease

vs.con

trol;↑:anincrease

vs.con

trol;(+):aslight

beneficialeffect;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect;(0):no

beneficialeffect;(-):intensification

oftheharm

fuleffect.

20 Oxidative Medicine and Cellular Longevity

Table7:The

protective

prop

erties

ofplantextractsagainstside

effectsof

antibiotics.

Reference

Plant

preparation,

dose,treatment

way

andtime,andanim

als

The

nameofdrug,dose,expo

sureway

andtime,andnegative

effects

Protectiveeffectsof

plantpreparation

Effectsof

plantperse

Valipou

retal.[98]

Ferulago

angulata

Ethanol:w

ater

(70:30,v/v)

extract

200,400,or

800mg/kg

b.w.,

p.o.,for

7days

MaleWistarrats,about

200g

Gentamicin

120mg/kg

b.w.,daily

for

7consecutivedays,i.p.

Serum:H

DL↓;TG,T

C,L

DL,

UA,

urea,C

R,P

C,T

NF-α,M

DA↑

Kidney:CAT,SODandAA↓,MDA

andrelative

expression

ofTNF-α↑

Serum:H

DL(0

200and400,+++800),C

R(+

200,++400and800),P

C(+

200,++400,+++800),

UAandurea

(++alld

oses),TC,L

DL,

TNF-αand

MDA(++200and400,+++800),T

G(++200,+++400and800)

Kidney:SO

D(0

200,++400and800),relative

expression

ofTNF-α(0

200,++400,+++800),

AA(0

200,+++400and800),C

AT(++200and

400,+++800),M

DA(++200,+++400and800)

Not

stud

ied

Borou

shaki

etal.[29]

Rheum

turkestanicum

root

70%

ethano

lextract

100or

200mg/kg,for

6days,i.p.,1

hour

before

gentam

ycin

MaleWistarrats,250-300

g

Gentamycin

80mg/kg/day,

for6days,i.p.

Serum:C

Randurea

↑Kidney:MDA↑,totalSH

content↓

Urine:p

rotein

andglucose↑

Serum:C

R,u

rea(++both

doses)

Kidney:MDA,totalSH

content(++both

doses)

Urine:p

rotein

(0100,++200),

glucose(+

100,++200)

Not

stud

ied

Apaydin

Yild

irim

etal.[28]

Helichrysum

plicatum

DC.sub

sp.

plicatum

aerialpartsethano

lextract

100or

200mg/(kg·d

)i.p.,for8days

MaleSprague-Daw

leyrats

Gentamicin

80mg/(kg·d

)i.p.,for8days

Serum:B

UN

andcreatinine

↑Liver:CATandSO

D↓;MDA,

degeneration

,necrosis,inflam

matory

cells, biliaryhyperplasia↑

Kidney:SO

D,C

AT,G

Px↓,MDA,

inflam

matorycells,d

egeneration,

necrosis↑

Serum:B

UN

andcreatinine

(++both

doses)

Liver:SO

D(++100,0200),M

DA(++100,+++200),

CAT(+++100,++200),n

ecrosis,degeneration

(++

100,+200),infl

ammatorycells

(+++100,+200),

biliary

hyperplasia(++both

doses)

Kidney:GPx(bothdo

ses),SOD(+++100,0200),

MDA,C

AT(+++100,++200)

Kidney:degeneration

andinflam

matorycells

(++100,+200),n

ecrosis(++both

doses)

Serum:B

UN

(↓100,↑200)

Liver:CAT(↓

200),infl

ammatory

cells,biliaryhyperplasiaandnecrosis

(↑200),d

egeneration

(↑both)

Kidney:CAT(↑

both

doses),

inflam

matorycells

andnecrosis

(↑200),d

egeneration

(↑both)

Zhang

etal.

[99]

Pana

xnotoginsengsapo

nins

(GuangxiWuzho

uPharm

aceutical

Co.,L

td.H

angzho

u,China)

10mg/kg,twiceadayfor

14days,i.m

.FemaleICRmice,18-20g

Polym

yxin-ind

uced

neph

rotoxicity

15mg/kg

twiceadayfor14

days,i.m

.Kidneyweight:body

weightratio:↑

Serum:B

UN,C

R↑

Kidney:SO

D↓,MDAandnu

mberof

apop

toticcells

↑

Kidneyweight:body

weightratio:(++)

Serum:B

UN,C

R(+++)

Kidney:nu

mberof

apop

toticcells

(++),

SODandMDA(+++)

Non

e

↓:adecrease

vs.con

trol;↑:anincrease

vs.con

trol;(+):aslight

beneficialeffect;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect;(0):no

beneficialeffect;(-):intensification

oftheharm

fuleffect.

21Oxidative Medicine and Cellular Longevity

Table8:The

protective

effectsof

plantpreparations

againstside

effectsof

anticancer

agents.

Reference

Plant

preparation,

dose,treatmentway

andtime,andanim

als

The

nameof

drug,d

ose,expo

sure

way

andtime,andnegative

effects

Protectiveeffectsof

plantpreparation

Effectsof

plantperse

Kim

etal.[100]

Dendropan

axmorbifera

The

CHCl 3fraction

of70%

methano

l

leafextract

25mg/kg

once

at24

hbefore

cisplatin

andon

ceadayfor5days

after,i.p.

SpragueDaw

leymalerats,

8weeks,about

200g

Cisplatin,a

singleadministrationof

6mg/kg,i.p.

Bod

yweight:↓

Kidney/body

weightratio:↑

Serum:B

UN,C

R↑

Kidney:SO

D↓,cleavedcaspase-3

andacutetubu

larnecrosisscore↑

Bod

yweight:(++)

Kidney/body

weightratio:(+++)

Serum:C

R(++),BUN

(+++)

Kidney:acutetubu

larnecrosisscore

(++),SO

Dandcleaved

caspase-3(+++)

Not

stud

ied

Kpemissi

etal.[102]

Com

bretum

micranthu

mleaf

ethano

l-water

(8:2)extract

200or

400mg/kg/day

p.o.,for

10days

MaleWistarrats,

6-8-week-aged,200-250

g

Cisplatin

7.5mg/kg,i.p.,

asingleinjectionon

the5thday

Bod

yweight:↓

Relativekidn

eyweight:↑

Serum:C

R,u

rea,UA,A

LT,A

ST,

GGT,A

LP↑,TP,A

LB,C

a,

Mg,P,N

O,F

RAP↓

Urine:C

R,u

rea,UA,P

↓,TP,A

LB,C

a,Mg,↑

Kidney:MDA↑,FR

AP,

NO,G

SH↓

Bod

yweight(++both

doses)

Relativekidn

eyweight:

(+++200,++400)

Serum:urea(+++200,++400),C

R,U

ATP,A

LB,

Ca,Mg,P,A

LT,A

ST,A

LP,N

O,F

RAP

(+++both

doses),G

GT(↓

both

doses)

Urine:C

R,u

rea,UATP,

(+++200,++400),A

LB,

Ca,Mg,P(+++both

doses)

Kidney:NO,G

SH(++both

doses),F

RAP

(+++200,++400),

MDA(+++both

doses)

Not

stud

ied

Hosseinian

etal.[16]

Nigellasativa

seeds70%

ethano

lextract

100or

200mg/kg,i.p.

(i)Pretreatm

ent(6

days)+salin

efor

5days

aftercisplatin

(ii)Pretreatm

ent(6

days)+extractfor

5days

aftercisplatin

MaleWistarrats,230-300

g

Cisplatin

6mg/kg

onthe6thdayof

theexperiment,i.p.

Serum:totalSH

↓,MDA↑

Kidney:totalSH

↓,MDA↑slightly

Renaltissue

damage:↑

(i)Serum:M

DA(+++both

doses),

totalSH

(+++100,↑200)

Kidney:MDA(-both

doses),

totalSH

(+++both)

Renaltissue

damage:(++both

doses)

(ii)Serum:M

DA(+++both

doses),

totalSH

(↑both)

Kidney:MDA(-100,+++200),

totalSH

(+++both)

Renaltissue

damage:(++both

doses)

Not

stud

ied

Chenetal.[25]

Totalflavon

oids

from

Clin

opodium

chinense(Benth.)

Pretreatm

ent

20,40,or

80mg/kg,i.g.,for15

days

MaleSprague-Daw

leyrats,220-250

g

Doxorub

icin-ind

uced

cardiotoxicity

3mg/kg,i.p.,everytwodays

fora

totalo

fthreeinjections

Bod

yandheartweight:↓

Serum:A

ST,L

DH,C

K↑

Heart:SOD,C

AT,G

Px↓,MDA↑

Bod

yandheartweight:

(++20,+

++40

and80)

Serum:C

K,L

DH

(++20,+

++40

and

80),AST

(+++alld

oses)

Heart:G

Px(+

20,+

+40

and80),CAT

(++alld

oses),MDA,SOD

(++20,+

++40

and80)

80mg/kg

only

stud

ied:

none

22 Oxidative Medicine and Cellular Longevity

Table8:Con

tinu

ed.

Reference

Plant

preparation,

dose,treatmentway

andtime,andanim

als

The

nameof

drug,d

ose,expo

sure

way

andtime,andnegative

effects

Protectiveeffectsof

plantpreparation

Effectsof

plantperse

Ahm

edetal.[24]

Allium

sativum

(garlic)aqueou

sextract

1mL/100gb.w.,p.o.,d

ailyfor7days

before

and7days

aftermetho

trexate

MaleWistarrats,100–120

g

Metho

trexate-indu

ced

neph

rotoxicity

20mg/kg,a

singleinjection,

i.p.

Serum:u

rea,CR,K

,P↑,Na↓

Kidney:GSH

,CAT↓,MDA,

ADA,N

O↑

Serum:u

rea(↓),P(+),

CR,K

,Na(+++)

Kidney:MDA,N

O(++),GSH

,CAT,A

DA(+++)

Non

e

Tag

etal.[37]

Morus

nigra(m

ulberry)

leaves

50%

ethano

lextract

500mg/kg,i.g.,daily

for14

days

Malealbino

rats,180–200

g

Metho

trexate-indu

ced

hepatotoxicity,a

singledo

se,

20mg/kg,on4thday,i.p.

Liverweight/body

weight:↑

Serum:A

ST,A

LT,A

LP,L

DH

↑Liver:totalp

atho

logicalscore

↑,meanscoreof

hepatocyte

degeneration

,con

gestion,

cellu

lar

infiltration,

fibrosis↑

Liverweight/body

weight:(++)

Serum:A

LP(++),AST

,ALT

,LDH

↓Liver:totalp

atho

logicalscore

(++),

meanscoreof

hepatocytedegeneration

,congestion

,cellularinfiltration

and

fibrosis(++)

Serum:A

ST,A

LT,

ALP

,LDH

↓

Moghadam

etal.[103]

CurcumalongaL.,ethanol

extract

100or

200mg/kg,p

.o.,for30

days

MaleWistarrats,220–280

g

Metho

trexate-indu

ced

hepatotoxicity,a

singledo

se

20mg/kg

i.p.,on

day30

th

Bod

yweight:

Liverweight:↑

Serum:A

LB,T

P↓,ALT

,AST

,ALP

,

bilirub

in↑

Plasm

a:TAS↓

Liver:SO

D,G

Px,CAT↓,MDA,

numberof

neutroph

ils,d

egree

ofinjury

↑

Bod

yweight:

Liverweightratio:(++both

doses)

Serum:A

ST,A

LP(++both

doses),

ALB

,ALT

,bilirubin,

TP

(++100,+++200)

Plasm

a:TAS(++100,+++200)

Liver:MDA,n

umberof

neutroph

ils(+

100,++200),d

egreeof

injury

(++both

doses),

SOD,C

AT,G

Px(++100,+++200)

The

higher

dose:

Liver:CAT↑

Plasm

a:TAS↑

Omole

etal.[26]

Kolaviron

—amixture

offlavon

oids

obtained

from

Garciniakolaseeds

Pretreatm

ent

200or

400mg/kg/d,p

.o.,for14

days

MaleWistarrats,120-150

g

Cycloph

osph

amide50

mg/kg/d,

i.p.,24

hoursafterthelastdo

seof

kolaviron,

for3days

Relativeheartweight:↑

Heart:SOD,C

AT,G

Px,GSH

↓,LD

H,C

K,M

DA,H

2O2,

MPO

andcT

nI↑

Relativeheartweight:

(+++200,++400)

Heart:LDH,C

K,cTnI,MPO,and

GSH

(++both

doses),G

Px,CAT,M

DA,

H2O

2(+++200,++400),

SOD

(+++)both

doses

Non

e

23Oxidative Medicine and Cellular Longevity

Table8:Con

tinu

ed.

Reference

Plant

preparation,

dose,treatmentway

andtime,andanim

als

The

nameof

drug,d

ose,expo

sure

way

andtime,andnegative

effects

Protectiveeffectsof

plantpreparation

Effectsof

plantperse

Shew

eita

etal.[101]

Essentialoilsof

Foeniculum

vulgareMiller

(fennel)seeds,

Cum

inum

cyminum

L.(cum

in)seeds,andSyzygium

arom

aticum

L.(clove)flow

erbu

ds(0.12mL/kg

b.w.,

0.10

mL/kg

b.w.,and0.106mL/kg

b.w.,(1/50LD

50do

ses),

respectively),p.o.for28

days

MaleSw

issalbino

mice,abou

t25

g

Cycloph

osph

amide

2.5mg/kg

b.w.for

28days,p

.o.

Serum:A

LT,A

ST,A

LP↑

Liver(S9fraction

):TBARS↑;GSH

,GPx,GR,G

ST,SOD,C

AT↓

Hepaticmicrosomalfraction

:NADPH-cytochrom

ec

redu

ctase↑

Serum:A

LT,A

ST,A

LP(++allo

ils)

Liver(S9fraction

):TBARS(++clove

oil,+++fenn

elandcumin

oils);GPx,

GSH

,GR,SOD,C

AT(+++allo

ils);

GST

↑allo

ilsHepaticmicrosomalfraction

:NADPH-

cytochromecredu

ctase

(0allo

ils)

Liver:TBARS↓,

GPx,CAT,G

ST↑(alloils),GR↑

(cum

inandclove),G

SH,SOD

↑(cum

in),NADPH-cytochrom

ec

redu

ctase↑(all)

Rahateand

Rajasekaran

[27]

Desmostachya

bipinn

ataStapf(L.)

roots—

thepo

lyph

enolicfraction

of70%

methano

lextract

100or

200mg/kg

b.w.,p.o.,21days

Sprague-Daw

leyfemalerats,150–200

g

Tam

oxifencitrate

45mg/kg

b.w.,p.o.,10th–21s

tdays

Serum:p

rotein

↓,AST

,ALT

,ALP

,

cholesterol,TG,u

rea,CR,

UA,bilirubin↑

Liver:LP

O↑,GSH

,GPx,

SOD,C

AT↓

Serum:p

rotein,A

ST,A

LT,cho

lesterol,

TG,u

rea,UA(++both

doses),C

R,

bilirub

in(++100,+++200),

ALP

(++100,↓200)

Liver:CAT(+

100,++200),LPO,G

SH,

GPx,SO

D,(++both

doses)

Not

stud

ied

↓:adecrease

vs.con

trol;↑:anincrease

vs.con

trol;(+):aslight

beneficialeffect;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect;(0):no

beneficialeffect;(-):intensification

oftheharm

fuleffect.

24 Oxidative Medicine and Cellular Longevity

Table9:The

protective

effectsof

plantpreparations

againstside

effectsof

variou

sdrugs.

Reference

Plant

preparation,do

se,treatmentw

ayandtime,

anim

als

The

nameof

drug,d

ose,expo

sure

way

andtime,

negative

effects

Protectiveeffectsof

plantpreparation

Effectsof

plant

perse

Ben

Saad

etal.[104]

Opu

ntiaficus-indica

cladod

eextracto

btainedby

homogenizationwith10

mM

TrisHCl,pH

7.4,

andsubsequent

centrifugation

Pretreatm

ent,100mg/kg

b.w.

30-day

pretreatmentandthen

for30

days

together

withlithium

MaleWistarrats,2

mon

ths

Li(lithium

carbon

ate),25mg/kg

b.w.,i.p.,

twicedaily

for30

days

Serum:glucose,T

C,T

G,A

LT,A

ST,

LDH,A

LP↑

Blood

:RBC,H

GB,H

CT↓,WBC↑

Liver:SO

D,C

AT,G

Px↓,MDA↑

Serum:A

LT,A

ST(++),glucose,TC,T

G,

ALP

,LDH

(+++)

Blood

:RBC,H

GB,H

CT,W

BC(++)

Liver:CAT(++),SO

D,G

Px,MDA(+++)

Non

e

Khalil

etal.[105]

Withaniasomnifera

leaf

70%

ethano

lextract

Pretreatm

ent,100mg/kg

b.w.,

for4weeks

MaleWistarrats,140–160

g

Isop

rotereno

l85mg/kg

b.w.,s.c.on

29thand30

th

days

Serum:T

C,T

G,V

LDL-c,cT

nI,C

K-M

B,

LDH,A

ST,A

LT↑,HDL-c↓

Heart:SOD,G

R,G

Px,GST

↓,MDA,w

eight↑

Serum:C

K-M

B(0),TC,T

G,V

LDL-c,

cTnI,L

DH

(++),HDL-c,AST

,ALT

(+++)

Heart:SOD,w

eight(++),GR,G

Px,

GST

,MDA(+++)

Serum:

HDL-c↑

Heart:G

Px,

GST

↑

Dianita

etal.[106]

Labisiapu

mila

var.alatawater

and80%

ethano

licextracts

100,200,or

400mg/kg,p

.o.,for28

days

MaleWistarrats,150-200

g

Isop

rotereno

l,85

mg/kg

ofs.c.,on29

thand30

th

dayof

theexperiment

Serum:cTnI,C

K-M

B,L

DH,A

ST,A

LT↑,

SOD,C

AT,G

Px↓

Heart:SOD,C

AT,G

Px↓

Serum:cTnI

(water

extract++alld

oses,

ethano

lextract++100and200,+++400),

CK-M

B,L

DH,A

ST,A

LT,SOD,C

AT,

GPx(++both

extractsalld

oses)

Heart:SOD,G

Px(w

ater

extract+100,++200

and400,ethano

lextract++alld

oses),

CAT(++both

extracts,alldo

ses)

Not

stud

ied

Shahat

etal.[107]

Rhu

stripartita80%methano

lextractof

thestem

partof

malegeno

type

250or

500mg/kg/day

p.o.,for

21days

(19-day-pretreatment)

MaleWistarrats,about

180g

Isop

rotereno

l85mg/kg,s.c.on20

thand21

stdays

Serum:A

ST,A

LT,G

GT,A

LP,L

DH,C

K,T

C,

TG,L

DL-c,VLD

L-c↑,H

DL-c↓

Heart:M

DA↑,NP-SH

andTP↓

Serum:L

DH,H

DL-c(+

250,++500),A

ST,

ALT

,GGT,A

LP,C

K,T

C,T

G,L

DL-c

andVLD

L-c(++both

doses)

Heart:M

DA,N

P-SH

andTP

(++both

doses)

Not

stud

ied

Kem

kaNguim

atio

etal.[108]

Afram

omum

melegueta

seed

water

and

methano

lextracts

20or

100mg/kg

for28

days

MaleWistarrats,sexually

experienced,

3-mon

th-old,200-250

g

Propylth

iouracil-indu

cedhypo

thyroidism

causingejaculatorycomplications

10mg/[kg·d

ay]for28

days

Plasm

a:T↓,TSH

andprolactin↑

Proejaculatoryactivity

(con

tractileactivity

ofthestriated

bulbospo

ngiosusmuscles):nu

mber

ofcontractions

aftertactile

stim

ulationand

pharmacologicalactivation

(dop

amine)

↓,intrasem

inalpressure

aftertactile

stim

ulationand

pharmacologicalactivation

(dop

amine)

↓

Water

extract:

Plasm

a:TSH

(0both

doses),T

(+20,+

++100),

prolactin(+

20,+

+100)

Proejaculatoryactivity:con

traction

snu

mber

afterboth

stim

uli(+++20,↑

100),intraseminal

pressure:tactilestim

ulation(↑

both

doses),

pharmacologicalactivation

(+++both

doses)

Methano

lextract:

Plasm

a:TSH

(020,+

100),T

(+20,+

+100),

prolactin(++20,+

100)

Proejaculatoryactivity:con

traction

snu

mber

afterboth

stim

uli(↑both

doses),intraseminal

pressure:tactilestim

ulation(↑

both

doses),

pharmacologicalactivation

(+++20,↑100)

Not

stud

ied

25Oxidative Medicine and Cellular Longevity

Table9:Con

tinu

ed.

Reference

Plant

preparation,do

se,treatmentw

ayandtime,

anim

als

The

nameof

drug,d

ose,expo

sure

way

andtime,

negative

effects

Protectiveeffectsof

plantpreparation

Effectsof

plant

perse

Nasrietal.

[109]

Green

tea70%

ethano

lextract

Posttreatment:afteriodixano

l,10

mg/kg/d,i.p.,for3days

Pretreatm

ent10

mg/kg/d,i.p.,for3

days

andiodixano

lonthe3r

dday

MaleWistarrats,6-w

eek-aged,200-250

g

Iodixano

l,acontrastmedium

10mL/kg,i.v.,asingledo

seRenaltubu

larcells:d

ilatation

,degeneration

,vacuo

lization,

debris↑

Posttreatment:

Renaltubu

larcells:d

ilatation

,degeneration

,vacuo

lization,

debris(++)

Pretreatm

ent:

Renaltubu

larcells:d

ilatation

,degeneration

,vacuo

lization,

debris(++)

Pretreatm

entshow

edaslightlybetter

effect

Not

stud

ied

El-Rahman

etal.[110]

Saussurealapparoots

70%

ethano

lextract

600mg/kg,p

.o.,daily

Cotreatmentfor2weeks

concurrently

withthedrug

Pretreatm

entfor1weekandthen

for2weeks

concurrentlywiththedrug

Malealbino

rats,150–160

g

Triam

cino

lone

aceton

ide

40mg/kg,i.p.,twiceaweekfor2weeks

Serum:T

NF-α,C

RP,IL-12,IgG

,IgM

↓Lu

ng:G

Px,SO

D↓,MDA↑

Spleen:G

Px,SO

D↓,MDA↑

Histopathologicallesion

score:spleen

andlung

↑

Cotreatment:

Serum:T

NF-αandCRP(0),IL-12and

IgG(+),IgM

(++)

Lung:G

Px(+),SO

D,M

DA(++)

Spleen:G

Px,SO

D,M

DA(++)

Histopathologicallesion

:spleen

andlung

(++)

Pretreatm

ent:

Serum:T

NF-α,IL-12,C

RP(0),IgG,IgM

(++)

Lung:G

Px,SO

D,M

DA(++)

Spleen:G

Px,SO

D(++),MDA(+++)

Histopathologicallesion

:spleenandlung

(++)

Serum:T

NF-α,

CRP,IL-12,↓,

IgG,IgM

↑Lu

ng:G

Px,

SOD↑,MDA↓

Spleen:G

Px,

SOD↑,MDA↓

↓:adecrease

vs.con

trol;↑:anincrease

vs.con

trol;(+):aslight

beneficialeffect;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect;(0):no

beneficialeffect.

26 Oxidative Medicine and Cellular Longevity

Table10:T

heprotective

effectsof

plantorigin

materialsin

theanim

almod

elof

arthritis.

Reference

Plant

extract,do

se,w

ayandtimeof

treatm

ent,

andanim

als

Indu

cing

factor

andnegative

effects

Protectiveeffectsof

plantmaterial

Effectsof

plant

perse

Cho

udhary

etal.[49]

Spinacia

oleracea

leaf

ethano

lextract

250or

500mg/kg/day,for

28days,p

.o.

Health

yandpathogen-freefemaleSprague-

Daw

leyrats,4–16weeks,180-200

g

Osteoarthritis,indu

cedby

mon

osod

ium

iodo

acetate,asingleinjectionof

3mgthroughthe

intra-articularjointof

theleftkn

eeSerum:G

ST,C

OMP↑

Urine:C

TX-II↑

Isolated

bone

region

containing

cartilage

andsub-

chon

dralbone:relativemRNAexpression

ofIL-1β,

TNF-α,C

OL1

0,MMP-1,M

MP-3,M

MP-13↑,

relative

mRNAexpression

ofBMP2,COL2

,AGGRECAN,T

IMP1,TIM

P2↓

Serum:C

OMP(+

250,++500),G

ST(++both

doses)

Urine:C

TX-II(+

250,++500)

Isolated

bone

region

containing

cartilage

andsub-chon

dralbone:relativemRNA

expression

ofTNF-αandMMP-13

(+250,++500);relativemRNAexpression

ofIL-

1β,C

OL1

0,MMP-1,M

MP-3

(++both

doses);

relative

mRNAexpression

ofBMP2,COL2

and

TIM

P1(0

250,++500),relativemRNAexpression

ofTIM

P2andAGGRECAN

(++both

doses)

Not

stud

ied

Jeon

getal.

[48]

Morus

alba

L.leafwater

extract

100mg/kg,p

.o.,on

ceperdayfor3weeks

MaleSpragueDaw

leyrats,180-240

g,5-week-old

Osteoarthritis,indu

cedby

mon

osod

ium

iodo

acetate,asingleinjection3mg/kg

into

therightkn

eejoint

Serum:IL-1β

,IL-6,TNF-α,INF-γ,

NO,P

GE2,COMP,C

TX-II↑

Articular

cartilage:expressionof

MMP-13↑

Serum:INF-γ(0),IL-1β,IL-6,TNF-α,

NO,P

GE2,

CTX-II,COMP(++)

Articular

cartilage:expressionof

MMP-13(++)

Articular

cartilage:a

slight

increase

inMMP-13

expression

Sund

aram

etal.[55]

Guggulip

id,anethylacetateextractrich

inlip

idsfrom

Com

miphora

whighitiigum

resin,

obtained

byextraction

ofgugguluoleoresin

(NKCAph

armacy,Musurum

India)

50or

100mg/kg/day,for

15days,p

.o.

Adu

ltWistarrats,10-week-old

Experim

entalarthritisindu

cedby

100μLof

FCA

(Freun

d’scompleteadjuvant

containing

10mg/mL

heat-killed

Mycobacterium

tuberculosis)injected

attheback

surfaceof

righthind

paw,s.c.

Blood

:WBC↑,RBC,H

GB,P

LT↓

Serum:expressionof

MMP-1,M

MP-3,

MMP-9,M

MP-13↑

Serum:A

LTAST

,SOD,C

ATandGST

↑Liverandspleen:R

OS,hydrop

eroxides,L

PO,P

C,

NO2- ,

GSSG,SOD,C

AT,G

ST↑,GSH

,GPx,GR↓

Ank

lejointho

mogenate:ACP,A

LP↑

Blood

:HGB(0

50,+

+100),W

BC,R

BC

(++bo

thdo

ses),P

LT(++50,+

++100)

Serum:M

MP-1

(+50,+

++100),M

MP-3

(+50,+

+100),M

MP-9

(++50,+

++100),

MMP-13(+++both

doses)

Serum:A

LT,A

ST,C

AT(++50,+

++100),

SOD

andGST

(+++both

doses)

Liver:ROS,hydrop

eroxides,G

Px,CAT(++both

doses),L

PO,P

C,N

O2- ,

SOD,G

SH,

GSSGandGR(++50,+

++100)

Spleen:R

OS,hydrop

eroxides

(++both

doses),

LPO,P

C,N

O2- ,

GR,G

SH,G

SSG(++50,+

++100),

SOD,C

AT,G

ST(+++both

doses)

Ank

lejointho

mogenate:ACP(+

50,+

+100),

ALP

(++both

doses)

Not

stud

ied

↓:adecrease

vs.con

trol;↑:anincrease

vs.con

trol;(+):aslight

beneficialeffect;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect;(0):no

beneficialeffect.

27Oxidative Medicine and Cellular Longevity

Table11:T

heprotective

effectsof

plantorigin

materialsin

theanim

almod

elof

neurod

egenerativedisorders.

Reference

Plant

extract,do

se,w

ayandtimeof

treatm

ent,

andanim

als

Disorder,indu

cing

factor,and

negative

effects

Protectiveeffectsof

plantmaterial

Effects

ofplant

perse

Hritcuetal.[32]

Pipernigrum

fruitsmethano

licextract50

or100mg/kg,p

.o.,daily,for

21days

MaleWistarrats,3

mon

th-old,about

250g

Animalmod

elof

Alzheim

er’sdisease

400pm

olAβ(1–42),i.c.v.,20

days

prior

tomethano

licextract

Amygdala:G

Px,GSH

↓,CAT,P

C,M

DA↑

The

lower

dose:

Bilateralamygdala:G

Px↑,GSH

(0),

PCandCAT↓,MDA(+++)

The

higher

dose:M

DA,P

C,C

AT↓,

GSH

(++),GPx(+++)

Not

stud

ied

Malik

etal.[39]

Celastrus

paniculatusseed

ethano

lextract

Pretreatm

entfor6days

100or

200mg/kg,

p.o.,and

then

treatm

entconcom

itantly

with3-nitrop

ropion

icacid

MaleWistarrats,220–250

g

3-Nitroprop

ionicacid-ind

uced

Hun

tington’sdiseasesymptom

s,10

mg/kg,i.p.,for14

days

Bod

yweight↓

Striatum

:MDA,N

O2-↑,CAT,SOD,G

SH↓

Cortex:MDA,N

O2-↑,CAT,SOD,G

SH↓

Bod

yweight:(++both

doses)

Striatum

:MDA,N

O2- ,

CAT,SOD,

GSH

(++both

doses)

Cortex:MDA,N

O2- ,

CAT,SOD,

GSH

(++both

doses)

Not

stud

ied

Cho

npatho

mpiku

nlert

etal.[31]

Apium

graveolens

L.,70%

methano

licextract

125,250,and375mg/kg

b.w.,p.o.,for

21days

MaleC57BL/6mice,2mon

ths,25–30g

Parkinson

’sdiseaseindu

cedby

1-methyl-4-

phenyl-1,2,3,6-tetrahydrop

yridine,15

mg/kg

perday,i.p.,dividedinto

4injections

at2h

intervalson

asingleday

Cortex:MDA,M

AO-A

,MAO-B

↑,GPx↓

Striatum

:MDA,M

AO-A

,MAO-B

↑,GPx↓

The

lowestdo

se:

Cortexandstriatum

:MAO-A

,GPx(0),MDA,

MAO-B

(++)

The

middledo

se:

Cortex:MAO-B

MAO-A

,GPx(++),

MDA(+++)

Striatum

:MAO-B

MAO-A

,GPx

andMDA(++)

The

highestdo

se:

Cortex:MDA,M

AO-B,M

AO-A

andGPx(+++)

Striatum

:MDA↓,MAO-B,M

AO-A

,GPx(+++)

Not

stud

ied

Wangetal.[38]

Rhizomadrynariae(a

commercialprod

uct)

madefrom

driedrootsof

Dryna

riafortun

eiwater

extract

20mg/kg

p.o.,d

aily,for

14or

28days

MaleSprague-Daw

leyrats,about

250g

Con

trolledcorticalim

pact(CCI)mod

elof

traumaticbraininjury

Plasm

a:IL-6

after1,3,7,14,21,and28

days

↑Brain:m

icroglialactivationafter1,3,7,

and14

days

↑

Plasm

a:IL-6

(0after3and7days,++after1day,

+++after14,21,and28

days)

Brain:m

icroglialactivation(0

after1day,

++after3,7,and14

days)

Not

stud

ied

Xuetal.[60]

Rhu

barb

(three

speciesareassigned

asoffi

cial

Rhu

barb,i.e.,Rheum

palm

atum

L.,R

heum

tanguticum

Maxim

.exBalf.,

andRheum

officina

leBaill),a

commercialprod

uct,water

extract

3,6,12

g/kg

ofRhu

barb

p.o.,after

trauma

MaleSprague-Daw

leyrats,200-300

gsacrificed

8,16,or24

hoursafterRhu

barb

Con

trolledcorticalim

pact(CCI)mod

elof

traumaticbraininjury

Brain

8hafterRhu

barb:M

DA↑,SO

D,

CAT,G

SH/G

SSG↓

Brain

16hafterRhu

barb:M

DA↑,SO

D,

CAT,G

SH/G

SSG↓

Brain

24hafterRhu

barb:M

DA↑,SO

D,

CAT,G

SH/G

SSG↓

Brain

8hafterRhu

barb:M

DAand

CAT(0

3and6,++12),SO

D(0

3,+6,++12),GSH

/GSSG

(+3,++6,+++12)

Brain

16hafterRhu

barb:M

DA

(03,++6and12),SO

D(++3and6,+++12),CAT

(03,++6and12),GSH

/GSSG(0

3,+6,++12)

Brain

24hafterRhu

barb:M

DA(++3and6,++

+12),SO

D(+

3,++6,+++12),CAT(0

3,++6

and12),GSH

/GSSG(+

3,++6,+++12)

Not

stud

ied

28 Oxidative Medicine and Cellular Longevity

Table11:C

ontinu

ed.

Reference

Plant

extract,do

se,w

ayandtimeof

treatm

ent,

andanim

als

Disorder,indu

cing

factor,and

negative

effects

Protectiveeffectsof

plantmaterial

Effects

ofplant

perse

Linetal.[113]

Uncaria

hirsuta95%

ethano

land

water

extractsof

stem

swithho

oks

80mg/kg/day

p.o.for4or

8weeks

MaleBALB

/cmice,8week-old

D-G

alactose-ind

uced

neurotoxicity

(12gin

100mLof

norm

alsalin

e)0.1mLper10

gof

weight,s.c.on

ceaday,

for4or

8weeks

Plasm

a4weeks:M

DA↑

Plasm

a8weeks:M

DA↑

Brain

8weeks:M

DA↑

Ethanol

extract:

Plasm

aMDA:4

weeks

(++),

8weeks

(+++)

Brain

MDA:8

weeks:(++)

Water

extract:

Plasm

aMDA:4

weeks

(++);

8weeks

(+++)

Brain

MDA:8

weeks

(++)

Not

stud

ied

Moh

aleetal.[111]

Nerium

indicum

flow

ersethylacetateextract

200and400mg/kg,oncedaily

p.o.

MaleSprague-Daw

leyrats,200–250

g

Anx

iety

indu

cedby

21-day

isolation

indark

room

Blood

:LPO

↑,SO

D,C

AT,G

SH↓

Brain:L

PO

↑,SO

D,C

AT,G

SH↓

Blood

:GSH

(+both

doses),

SOD(++both

doses),C

AT

(++200,+++400),L

PO

(+++both

doses);

Brain:C

AT(++)both

doses,SO

DandGSH

(++200,+++400),L

PO

(+++both

doses)

Not

stud

ied

Wuetal.[112]

Malva

sylvestrisL.

leafandflow

er95%

methano

lextract

250mg/kg

perday,i.g.,for7days

Adu

ltSP

F-grademice

Lipo

polysaccharide-ind

uced

depression

250μg/kg

i.p.,adaybefore

treatm

ent(priorto

injectionsulin

dacsulfide

3.75

or7.5mg/kg

for>3

weeks)

Cortex:astroglio

sis,IL-1,IL-6,TNF-α↑,

numberof

survivalneuron

s↓

Hippo

campu

s:astroglio

sis,IL-1,IL-6,

TNF-α↑,nu

mberof

survivalneuron

s↓

Cortex:nu

mberof

survivalneuron

s,astroglio

sis,IL-1,IL-6,TNF-α(++)

Hippo

campu

s:nu

mberof

survivalneuron

s,astroglio

sis,IL-1,IL-6,TNF-α(++)

Not

stud

ied

↓:adecrease

vs.con

trol;↑:anincrease

vs.con

trol;(+):aslight

beneficialeffect;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect;(0):no

beneficialeffect.

29Oxidative Medicine and Cellular Longevity

Table12:T

heprotective

effectsof

plantorigin

materialsin

theanim

almod

elof

menop

ause.

Reference

Plant

extract,do

se,w

ayandtimeof

treatm

ent,

andanim

als

Indu

cing

factor

andnegative

effects

Protectiveeffectsof

plantmaterial

Effectsof

plantperse

Leun

getal.[115]

Cam

ellia

sinensisO.K

tze(black

tea)

extract(Q

P-lackteaextract,

QualityPhytochem

icalsLL

C)

15mg/kg/day,i.g.,for4weeks,3

mon

ths

afterovariectom

yFemaleSprague-Daw

leyrats,

3mon

ths,200–230g

Ovariectomy

Bod

yweight:↑

Serum:17β

-estradiol,cGMP↓,no

n-HDL-c,HDL-c,TC,T

G↑

Aorta:p

eNOS↓,NOX2,NOX4↑

End

otheliu

mof

aorta:ROS↑

Bod

yweight:(0)

Serum:T

G↓,17β-estradiol,

non-HDL-c(0),HDL-c,TC

(++),cG

MP(+++)

Aorta:p

eNOS,NOX2,NOX4(+++)

End

otheliu

mof

aorta:ROS(+++)

Not

stud

ied

Galanisetal.[114]

Glycyrrhiza

glabra

root

methano

lextract,in

theform

ofdrinking

water

atsuch

avolume

soas

toobtain

theup

perthresholdof

glycyrrhizin

(the

mainactive

compo

nent)

of12.4mg/kg/rat

perday,adayaftersurgery,

for3or

6mon

ths

FemaleintactmatureWistar

rats,10mon

ths

Ovariectomy

Totaltibiabone

mineraldensity:after3

and6mon

ths↓

Proximaltibiabone

mineraldensity:

afterboth

3and6mon

ths↓

Uterine

weight:after6mon

ths↓

Totaltibiabone

mineraldensity:(+++after3

mon

ths,++after6mon

ths)

Proximaltibiabone

mineraldensity:

after3mon

ths(+++),after6mon

ths(++)

Uterine

weight:(++)

Not

stud

ied

Ham

metal.[116]

Hum

ulus

lupu

lusL.,h

opsflavon

oid-rich

extract

(MetaG

enics,AlisoViejo,C

A,U

SA)

400mg/kg

infood

,daily,for

11weeks

FemaleC57BL/6mice,7mon

ths

Ovariectomy

Uterusweight↓

Visceraladipo

setissue

weight↑

Liver:TG↑

Ileum:A

LP↑

Uterusweight(0)

Visceraladipo

setissue

weight(+)

Livertriglycerides(+++)

Ileum: A

LP(0)

Uterusweight

↓Ileum:A

LP↑

↓:adecrease

vs.con

trol;↑:anincrease

vs.con

trol;(+):aslight

beneficialeffect;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect;(0):no

beneficialeffect.

30 Oxidative Medicine and Cellular Longevity

Table13:T

heprotective

effectsof

plantorigin

materialsin

lung

disorders.

Reference

Plant

extract,do

se,w

ayandtimeof

treatm

ent,and

anim

als

Indu

cing

factor

andnegative

effects

Protectiveeffectsof

plantmaterial

Effectsof

plantperse

Taguchi

etal.[118]

Saku

ranetin,

aflavon

oidobtained

from

methano

lextractof

aerialpo

rtions

ofBaccharisretusa

bysuccessive

extraction

andseparation

from

CH

2Cl 2

phase

Posttreatment-20mg/kg

viaintranasalinstillationon

days

0,7,14,and

28(the

endof

theexperiment)

C57BL6

malemice,7-9-week-old,

25g

Emph

ysem

aindu

cedby

elastase,50μL

(6.6un

its/mg),anintranasaldrop

(0.667

IU)

BALF

:macroph

ages,lym

phocytes,

neutroph

ils,eosinop

hils,totalcells

↑Lu

ng:N

F-κB

,M-C

SF,IL-1β

,MCP-1,T

NF-α

↑,expression

ofTIM

P-1,M

MP-9,M

MP-12↑

Lung:collagenandelasticfiberdepo

sition

↑

BALF

:eosinop

hils(-),macroph

ages,

lymph

ocytes,n

eutrop

hils,totalcells

(++)

Lung:M

CP-1

(+),M-C

SF,IL-1β

,TNF-α,N

F-κB

(+++),expression

ofTIM

P-1

↑,expression

ofMMP-9,M

MP-12(++)

Lung:collagenandelasticfiberdepo

sition

(++)

BALF

:eosino

phils

↑

Kaveh

etal.[117]

Portulacaoleracea

leaves,70%

ethano

lextract

1,2and4mg/mLin

drinking

water

for21

days

MaleWistarrats,about

220g

Asthm

aratssensitized

ondays

1,2,and3

by1mg/kg

ofovalbu

min

(OVA)+100mg

Al(OH) 3,i.p.,andexpo

sedto

1%OVAaerosol

for20

min

ondays

6,9,12,15,18,and

21Serum:thiol,SOD,C

AT↓,NO2- ,

NO3- ,

MDA↑

Blood

:lym

phocytes↓,totalW

BC,eosinop

hils,

neutroph

ils↑

Serum:thiolandMDA(0

1,+2,++4),SOD(0

1,+2,+++4),C

AT(0

1,++2and4),N

O2-(++

1,+++2and4),N

O3-(++alld

oses)

Blood

:neutrop

hilsandlymph

ocytes

(01,++2,

+++4),eosinop

hils(0

1,+++2and4),total

WBC(+++alld

oses)

Not

stud

ied

Wangetal.[119]

Salviamiltiorrhiza

Bge.f.albaroot

aqueou

sextract

4.6or

14g/kg

b.w.d

ailyin

thedrinking

water,21days

afterMCT

MaleSprague-Daw

leyrats,200-220

g

Pulmon

aryhypertension

anim

almod

elcaused

bymon

ocrotalin

e(M

CT)—

asingle

dose

of60

mg/kg

b.w.,s.c.

Meanpu

lmon

aryartery

pressure,right

ventricularsystolicpressure

↑Plasm

a:NO,6-K

eto-PGF1

α↓,

ET-1

andTXB2↑

Lung:T

GF-β1↑

Meanpu

lmon

aryartery

pressure

andright

ventricularsystolicpressure

(++both

doses)

Plasm

a:6-Keto-PGF1

αandTXB2(++both

doses),N

O,E

T-1

(++4.6,+++14)

Lung:T

GF-β1(++both

doses)

Not

stud

ied

↓:adecrease

vs.con

trol;↑:anincrease

vs.con

trol;(+):aslight

beneficialeffect;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect;(0):no

beneficialeffect;(-):intensification

oftheharm

fuleffect.

31Oxidative Medicine and Cellular Longevity

Table14:T

heprotective

effectsof

plantorigin

materialsin

lipid

profi

ledisturbances.

Reference

Plant

extract,do

se,w

ayandtimeof

treatm

ent,andanim

als

Indu

cing

factor

andnegative

effects

Protectiveeffectsof

plantmaterial

Effectsof

plant

perse

deToledoEspindo

laetal.[121]

Cam

poman

esia

adam

antium

root

aqueou

sextract

200mg/kg

b.w.,p.o.,8

weeks

after

hyperlipidem

iaWistarrats,60days,140-150

g

Hyperlip

idem

iaindu

cedby

high

fructose

dietfor16

weeks

Bod

yweightgain:↑

Serum:T

C,T

G↑

Bod

yweightgain:(++du

ring

theexperiment,

+in

theend)

Serum:T

C,T

G(+++)

Not

stud

ied

Veber

etal.[34]

Brassicaoleracea

L.redcabbage

aqueou

sextract

125or

250mg/kg,p

.o.,twiceaday,

for3days

MaleWistarrats,200-300

g

Hyperlip

idem

iaindu

cedby

asingleadministrationof

TritonWR-1339

400mg/kg,i.p.

Serum:M

DA,P

C↑

RBC:SOD↑,CAT↓

Liver:MDA,P

C,SOD,G

Px↑,CAT↓

Kidney:MDA,P

C,G

Px↑,SO

D,C

AT↓

Cerebralcortex:SO

D↓,MDA,P

C↑

Hippo

campu

s:SO

D,C

AT↓,GPx,MDA↑

Serum:M

DA(0

both

doses),P

C(0

125,+++250)

RBC:C

AT(0

125,+++250),SOD

(+++both

doses)

Liver:CAT(0

125,+++250),P

C(+++125,++250),

MDA,SOD,G

Px(+++both

doses)

Kidney:MDA(0

both

doses),G

Px

(0125,+++250),

PC,SOD,C

AT(+++both

doses)

Cerebralcortex:SO

D(0

125,+++250),P

C(++125,+++250),M

DA(+++both

doses)

Hippo

campu

s:SO

D(0

125,+++250),M

DA

(++125,+++250),C

ATandGPx

(+++both

doses)

Not

stud

ied

Khlifi

etal.[120]

EricamultifloraL.

leafmethano

licextract

Pretreatm

ent150or

250mg/kg,i.g.,

1ho

urbefore

TritonWR-1339

MaleWistarrats,150-200

g

TritonWR-1339-indu

cedhyperlipidem

ia,a

single

dose

300mg/kg,i.p.

Serum:H

DL-c↓,TC,T

G,V

LDL-c,LD

L-c↑

Plasm

a:ALT

,AST

↑Liver:SO

D,G

Px,CAT↓,MDA↑

Liver:totalD

NAdamage↑

Serum:H

DL-c(0

150,++250),T

G,

VLD

L-c,LD

L-c

(++both

doses),T

C(++150,+++250)

Plasm

a:ALT

(++150,+++250),A

ST(+++both

doses)

Liver:SO

D(+

150,++250),M

DA

(++both

doses),

GPx(+

150,+++250),C

AT(++150,++250)

Liver:totalD

NAdamage(++both

doses)

250mg/kg

only

stud

ied:

Serum:V

LDL-c,

TG↑

Liver:SO

D↑

Onyenibeetal.[122]

Monodoramyristica

fruitaqueou

sextract

100or

200mg/kg

b.w.,p.o.,fi

vetimes

aweekfor8weeks

MaleWistaralbino

rats,120-140

g

Hypercholesterolemiaindu

cedby

cholesterol,p.o.

40mg/kg/0.3mL,

five

times

aweekfor8weeks

Serum:H

DL-c↓,LD

L-c,TC,T

G,A

ST,A

LT↑

Liver:SO

D,C

AT,G

SH↓,MDA↑

Heart:SOD,C

AT↓,MDA↑

Serum:L

DL-c(0

100,+200),A

ST,T

C(++both

doses),T

G,A

LT(+++both

doses),

HDL-c(↑

both

doses)

Liver:MDA(++both

doses),SOD,C

AT,

GSH

(+++)both

doses

Heart:M

DA(++100,+++200),SOD

(+++)both

doses,CAT(↑

both

doses)

Not

stud

ied

↓:adecrease

vs.con

trol;↑:anincrease

vs.con

trol;(+):aslight

beneficialeffect;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect;(0):no

beneficialeffect.

32 Oxidative Medicine and Cellular Longevity

Table15:T

heprotective

effectsof

plantorigin

materialsin

anischaemia/reperfusion

mod

el.

Reference

Plant

extract,do

se,w

ayandtimeof

treatm

ent,andanim

als

Indu

cing

factor

andnegative

effects

Protectiveeffectsof

plantmaterial

Effectsof

plantperse

Casku

rlu

etal.[124]

Nigella

Sativa

seedsoil

Pretreatm

ent,asingledo

seof

400mg/kg

p.o.,3

days

before

reperfusion

MaleSprague-Daw

leyrats,250-300

g,10-12weeks

Renalreperfusioninjury

45min

occlusionof

thebilateralrenalpedicles

+reperfusion(24h)

Kidney:tubu

lointerstitialdamage↑,glom

erular

injury

score↑,GPx,CAT↓,MDA↑

Kidney:tubu

lointerstitialdamage(++),

glom

erular

injury

score(++),GPx,CAT,

MDA(++)

Not

stud

ied

Sravanthiand

Rao

[126]

Pentapetes

phoeniceamethano

licextract

Pretreatm

ent,for10

days

100,200or

400mg/kg/day

MaleWistarrats,300–350

g

Globalcerebralischemiaindu

cedby

tempo

rary

bilateralcarotid

artery

occlusion(30min)

andsubsequent

4hreperfusion

Brain:w

eight,water

andproteincontent,infarct

volumeandLP

O↑,SO

D,C

AT,G

SH,G

Px,GR,G

ST↓

Brain:w

eight,water

andproteincontent,

infarctvolume,MDA,SOD,C

AT,G

SH,

GPx,GR,G

ST(++alld

oses)

The

greaterthedo

sethebetter

theeffect

Not

stud

ied

Cakir

etal.[123]

Hypericum

perforatum

80%

ethano

lextract

50mg/kg,i.p.,at

thebeginn

ingof

ischem

iaMaleSprague-Daw

leyrats,300–350

g

Right

neph

rectom

yandsubsequent

ischaemia

(45min)/reperfusion(3h)

oftheleftkidn

eySerum:B

UN

andcreatinine

↑Kidney:CAT,SOD,G

Px↓,MDA↑

Kidney:hydrop

icchanges,tubu

lardilation

,tubu

lardesquamationcongestion

↑

Serum:B

UN

andcreatinine

(-)

Kidney:CAT,SOD,G

PxandMDA(+++)

Kidney:tubu

lardesquamationcongestion

,hydrop

icchanges,tubu

lardilation

(++)

Not

stud

ied

God

inho

etal.[125]

Trichiliacatiguaethyl-acetatefraction

ofaceton

e-water

(7:3)extract

200mg/kg,0.5hbefore

and1haftersurgery

(totaldo

se400mg/kg),p.o.

MaleWistarrats,3-m

onth-old

Cerebralischaem

ia-reperfusion

4-VO

mod

elof

transientglobalcerebralischaemia,15min

ischaemia

Brain:G

SH,G

SH/G

SSG,C

AT,SOD

↓,GSSG, P

CG,M

DA↑

Brain:C

AT(0),GSH

,GSSG,G

SH/G

SSG,

SOD,P

CG,M

DA(+++)

Not

stud

ied

↓:adecrease

vs.con

trol;↑:anincrease

vs.con

trol;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect;(0):no

beneficialeffect;(-):intensification

oftheharm

fuleffect.

33Oxidative Medicine and Cellular Longevity

Table16:T

heprotective

effectsof

plantorigin

materialsin

anim

almod

elsof

diabetes.

Reference

Plant

extract,do

se,w

ayandtimeof

treatm

ent,andanim

als

Indu

cing

factor

andnegative

effects

Protectiveeffectsof

plantmaterial

Effectsof

plantper

se

Ben

Salem

etal.[128]

Cynarascolym

usleaves

75%

ethano

lextract

200or

400mg/kg

b.w.d

aily,p

.o.,

for28

days

MaleWistarrats,10-12-w

eek-old,

160–200g

Alloxanmon

ohydrate-ind

uced

diabetes,a

singledo

se150mg/kg

b.w.,i.p.

Bod

yweightgain:↓

Blood

glucose:↑

Serum:α

-amylase,pancreaticlip

ase,ALT

,AST

,ALP

,urea,CR↑

Plasm

a:TG,T

C,L

DL-c↑,HDL-c↓

Blood

:RBC,W

BC,H

GB,P

LT↓

Liver:SO

D,C

AT,G

SH↓,MDA,A

OPP↑

Pancreas:SO

D,C

AT,G

SH↓,MDA,A

OPP↑

Kidney:SO

D,C

AT,G

SH↓,MDA,A

OPP↑

Bod

yweightgain:(+++both

doses)

Blood

glucose:(+++200,++400)

Serum:A

LP(++both

doses),u

rea(++200,+++400),

CR(+++200,++400),A

LT,A

ST,α

-amylase,

pancreaticlip

ase(+++both

doses)

Plasm

a:TG,T

C,L

DL-c,HDL-c(+++both

doses)

Blood

:WBC(0

200,++400),P

LT(++both

doses),

RBCandHGB(+++both

doses)

Liver:MDA,SOD,C

AT,A

OPP(+++both

doses),

GSH

(+++200,↑400)

Pancreas:SO

D(++both

doses),M

DA,C

AT

(+++200,++400),G

SH,A

OPP(+++both

doses)

Kidney:SO

D(+

200,++400),C

AT(+++200,++400),

GSH

,MDA,A

OPP(+++both

doses)

Not

stud

ied

Dra

etal.[127]

Carallumaeuropaea

aerialpartextract

obtained

bysuccessive

extraction

with

dichloromethane

andmethano

l250or

500mg/kg

b.w.,p.o.,a

singledo

se,

followed

for10

hSw

issalbino

mice,8weeks

Alloxanmon

ohydrate-ind

uced

diabetes

type

1,asingledo

seof

200mg/kg

b.w.,i.p.

Blood

:glucose

↑Isletsdiam

eter:↓

The

lower

dose:

Blood

glucose:after2,4,and6h(++),after8

h(+++)

andafter10

h(↓);isletdiam

eter

(++)

The

higher

dose:

Blood

glucose:after2(++),after4and6h

(+++),after8and10

h(↓)

Not

stud

ied

Silvaetal.[59]

Musa×paradisiacaL.greenbanana

pasta

Com

mercialfeed

containing

25,50,or

75%

ofgreenbanana

pasta,for12

weeks

MaleWistarrats,6-8

weeks

old,180-300g

Alloxan-indu

ceddiabetes,type1,i.p.,asingle

dose

of150mg/kg

Serum:glucose,A

LT,A

ST,T

C,T

G,

fructosamine↑

Liver:totallipids,LP

OandPC↑

Kidney:PC↑

Serum:A

ST(0

alld

oses),glucose,fructosamine(+

25and50,+

++75),TC(0

25,+

++50,0

75),ALT

(025,+

++50

and75),TG(+++alld

oses)

Liver:totallipids(+

25and50,+

++75),LP

O(0

25,+

++50,↓

75),PC(0

25,+

+50,+

++75)

Kidney:PC(0

25,+

++50,↓

75)

Not

stud

ied

Duetal.[66]

Polysaccharideseparatedfrom

Lycium

barbarum

100,250,or

500mg/kg,p

.o.,for4weeks

MaleSpragueDaw

leyrats

8weeks

old,

180–220g

High-fatdietfor8weeks

andthen

diabetes

indu

cedby

streptozotocin

injection,

30mg/kg

foraweek

Fastingbloodglucose:↑

Serum:insulin,SOD,G

Px↓,BUN,IL-2,IL-6,

TNF-α,INF-α,M

CP-1,ICAM-1

↑Urine:A

LB↑

Fastingbloodglucose:(+

100,++250,and500)

Serum:INF-α(0

100and250,++500),insulin,IL-2,

ICAM-1

(0100,+250,++500),SOD,T

NF-α,B

UN

(0100,+250,+++500),G

Px,IL-6

(0100,+++250and

500),M

CP-1

(+250,+++250and500)

Urine:A

LB(+

250,++250and500)

Not

stud

ied

Wattanathorn

etal.[42]

The

combination

of50%

hydroalcoh

olic

extractsof

Man

gifera

indica

L.seedsand

Polygonu

modoratum

L.aerialparts

prepared

ataratio1:5

2,10,or50

mg/kg

b.w.,daily,for

10weeks

MaleWistarrats,180–220

g

Diabetescataractandretino

pathyindu

cedby

asingleinjectionof

streptozotocin

55mg/kg

b.w.

Blood

glucoseafter5and10

weeks

↑Grade

ofcataractseverity

↑Totalretinalthickness

↓Lens:SOD,C

AT,G

Px↓,MDA,V

EGF,ERK1/2,

p38M

APK,A

R↑

Lens:opacity

index↑

Blood

glucoseafter5weeks:(+2and50,+

+10)

Blood

glucoseafter10

weeks:(+2,010,-

50)

Totalretinalthickness:(++2and10,0

50)

Grade

ofcataractseverity:(++alld

oses)

Lens:SOD(++2,+10,-

50),MDA(++2and10,0

50),

GPx(+

2and50,++10),CAT,A

R,ERK1/2,p38M

APK

(++alld

oses),VEGF(+

2,++10,+

++50)

Lens:opacity

index(++alld

oses)

Not

stud

ied

34 Oxidative Medicine and Cellular Longevity

Table16:C

ontinu

ed.

Reference

Plant

extract,do

se,w

ayandtimeof

treatm

ent,andanim

als

Indu

cing

factor

andnegative

effects

Protectiveeffectsof

plantmaterial

Effectsof

plantper

se

Balbaa

etal.[57]

Nigella

sativa

seed

oil

2.0mL/kg

b.w.,i.g.,for21

days

after

diabetes

developm

ent

MaleWistarrats,about

125g

Type2diabetes

indu

cedby

ahigh-fat

dietfor2

weeks,followed

byasingleinjectionof

streptozotocin

35mg/kg,i.p.

Serum:T

NF-α,IL-6,AGE↑

Brain:T

BARS,XO,N

O,T

NF-α,IL-6,IL-1β,

iNOS,AGE,A

ChE

,Aβ-42,ID

E↑,GSH

,GPx,

GST

,SOD,glucose

↓

Serum:T

NF-α,IL-6(+++),AGE↓

Brain:A

ChE

(↓),TBARS,XO,IL-6,IL-1β(++),NO,

TNF-α,iNOS,GSH

,GST

,SOD,A

GE,A

β-42,ID

E,

glucose(+++),GPx(↑)

Serum:IL-6

andAGE↓

Brain:A

ChE

and

Aβ-42↓,TBARS,

NO,IDE,G

Px,

GST

,SOD↑

Fajri

etal.[131]

Equisetumarvenseaerialparts,methano

licextract

250or

500mg/kg

b.w.,daily

p.o.,for

45days

afterdiabetes

indu

cing

Malemice,6-8weeks

Streptozotocin-ind

uced

diabetes,

50mg/kg

b.w.i.p.,for5days

Sperm:viability,motility

↓,percentage

ofmorph

ologicalabno

rmalities,DNAdamage

andnu

clearim

maturity↑

The

lower

dose:viability,percentage

ofmorph

ological

abno

rmalitiesandDNAdamage(++),motility

and

percentage

ofnu

clearim

maturity(+++)

The

higher

dose:viability,motility

(++),percentage

ofmorph

ologicalabno

rmalities,DNAdamageand

nuclearim

maturity(+++)

Not

stud

ied

Khanra

etal.[129]

Abrom

aau

gustaL.

leaf

methano

lextract

100or

200mg/kg,p

.o.,daily

for4weeks

MaleWistarrats,2–3-m

onth-old,

abou

t180g

Type2diabetes

indu

cedby

asingleinjectionof

streptozotocin

65mg/kg

i.p.,15

min

later

nicotinamide110mg/kg,i.p

.Fastingbloodglucose:↑

Serum:H

DL-c,insulin

↓,TC,T

G,H

bA1c,

ALT

,AST

,urea,LD

H,C

K,C

RP↑

Kidney:DNAfragmentation

,ROS,TBARS,PC,

IL-1β,IL-6,TNF-α,↑,totalcoenzymes

Q9and

Q10,G

SH,C

AT,SOD,G

ST,G

Px,GR,G

6PD,

ATP,B

cl-2/Bax

↓Kidney:expression

ofNF-κB

,PKC(α,β

,δ,ε),caspase3,caspase9↑

Heart:R

OS,TBARS,PC,IL-1β

,IL-6,TNF-α,

GPx,GR,D

NAfragmentation

↑,total

coenzymesQ9andQ10,G

SH,C

AT,SOD,G

ST,

G6P

D,A

TP,B

cl-2/Bax

↓Heart:expressionof

NF-κB

,caspase

3,caspase9,PKC(α,β

,δ,ε)↑

Fastingbloodglucose:(++both

doses

Serum:T

C,T

G,H

bA1c,A

LT,A

ST,u

rea,LD

H,

CK,C

RP,insulin

(++both

doses),

HDL-c(++100,+++200)

Kidney:ROS,TBARS,PC,totalcoenzymeQ9,SO

D,IL-

1β,IL-6,TNF-α,D

NAfragmentation

,ATPandBcl-

2/Bax

(++both

doses),totalcoenzymeQ10,G

SH,

GST

,GPx,GR,G

6PD(++100,+++200),C

AT

(+++both

doses)

Kidney:expression

ofNF-κB

,PKC(α,β

,δ,ε),

caspase3,caspase9(++both

doses)

Heart:R

OS,TBARS,PC,G

SH,C

AT,SOD,IL-1β

,IL-6,

TNF-α,A

TP,B

cl-2/Bax,D

NAfragmentation

(++both

doses),G

ST,G

6PD(++100,+++200),totalcoenzymes

Q9andQ10

(+++both

doses),G

Px,GR(↑

both

doses)

Heart:expressionof

PKC(α,β

,δ,ε),caspase3,caspase

9(++both

doses),N

F-κB

(+++both

doses)

Not

stud

ied

Omod

anisi

etal.[130]

Moringa

oleifera

leafextractobtained

bysuccessive

extraction

withn-hexane

and

80%

methano

l,250mg/kg

b.w.,p.o.,

for6weeks

MaleWistarrats,10weeks

Streptozotocin-ind

uced

diabetes,a

singledo

seof

55mg/kg,i.p.

Plasm

a:glucose↑

Serum:T

P,A

LB↓

Kidney:weightandrelative

weight↑

Kidney:GPx,SO

Dslightly↓,CAT↓,

TNF-αslightly↑,

MDA,IL-6↑

Plasm

a:glucose(++)

Serum:A

LB(+),TP(+++)

Kidney:weightandrelative

weight(++)

Kidney:GPx(-),CAT(0),TNF-α,IL-6(+),

SOD(++),MDA(+++)

Plasm

a:glucose↓

Serum:T

P,A

LB↑

Kidney:SO

D↑,

GPx,IL-6,

TNF-α↓

↓:adecrease

vs.con

trol;↑:anincrease

vs.con

trol;(+):aslight

beneficialeffect;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect;(0):no

beneficialeffect;(-):intensification

oftheharm

fuleffect.

35Oxidative Medicine and Cellular Longevity

the protective effect of plant preparations which involvedimprovement of oxidative balance by activation of theNrf2/HO-1 antioxidant pathway [61] and the amelioratingeffect on lipid status [132, 133]. The latter was also confirmedin vitro as the lipolysis-promoting influence in 3T3-L1 cellswas observed [61]. In mice fed a high-fat diet, coadministra-tion of Euterpe oleracea extract reversed the changes of lipo-genic proteins expression in the liver. Additionally, theinvestigated preparation increased hepatic expression ofABCG5 and ABCG8 transporters responsible for removingexcess of cholesterol by secretion into bile [43].

The detailed results of the performed studies are collectedin Table 17.

2.10.9. The Protective Influence of Plant Preparations againstGastric Ulcer-Inducing Factors. The gastric ulcers areregarded as the most common disease of gastrointestinaltract, but they can be caused by many various factors. Ther-apy of different disorders with using nonsteroidal anti-inflammatory drugs like indomethacin and excessiveconsumption of alcohol belong to important ones [45, 134].As pharmaceutical agents are not fully effective and theirapplication may also be connected with development of sideeffects, an alternative ways of treatment became the subjectof research. Plant origin substances showed a wide rangeof beneficial effects, including alleviated or reversed oxida-tive stress which was found to be involved into gastriculcer etiology as well as mechanism of indomethacintoxicity [135–137].

The detailed results of the performed studies are pre-sented in Table 18.

2.10.10. The Protective Effects of Plant Origin Materials inAnimal Model of Different Disorders. The symptoms of manyother various disturbances were affected in a positive way byusing plant materials of experimentally confirmed antioxi-dant properties and containing acknowledged antioxidantslike phenolic acids and flavonoids [36, 41, 138]. A wide rangeof diseases: lithiasis, thyroid disorders, retinal degeneration,irritable bowel syndrome, hyperthyroidism, periodontitis,and mammary gland hyperplasia, were studied, pointing togreat possibilities “hidden” in plant origin agents.

The details of the performed studies are presented inTable 19.

2.11. The Protective Effects of Plant Origin Materials againstRadiation. Plant extracts also showed some efficacy againstradiation-induced damage. The research revealed theinvolvement of JAK-STAT pathway into the mechanism ofthe protective influence on the hematopoietic system [70].Animal studies also showed the reversing effect of plantmaterial on the disturbances of antioxidant defence causedby γ-radiation in blood and organs [145, 146]. One of therecent in vitro investigations, performed on keratinocytecells, confirmed the antioxidant action of a plant preparationagainst UVB radiation, which could contribute to develop-ment of new skin protective strategies [147].

The details of the performed studies are presented inTable 20.

3. The Comparison of Plant Preparations withStandard Drugs and Supplements: TheDependence of Effects on Treatment Wayand Doses

The effects of plant origin materials were often investigatedin comparison with those shown by standard drugs. Theresults clearly show that there may be a possibility to replacedifferent medicines with plant preparations which do notcause so many severe side effects, but the detailed researchmust be performed before the final conclusions can be made.

The question of advantage of plant origin extracts overany standard drug is complicated, and a univocal answer isvery difficult as in some cases the differences in the influenceof the compared agents were strongly dependent on theapplied dose [45, 135] and studied parameters [115, 129].

Hamm et al. [116] found that hops (Humulus lupus L.)flavonoid-rich extract protected against ovariectomy-induced visceral adiposity and increase in liver triglyceridesobserved in 7-month-old retired breeder C57BL/6 mice.However, particularly in case of the former parameter, theobserved effect was not so distinct as that noted in animalsreceiving 17-β-estradiol. Additionally, hops extract couldnot prevent the loss of uterus weight caused by the surgerywhile estrogen showed quite a considerable reversing effect.

Leung et al. compared the effect of black tea extract withthat exerted by estrogen in ovariectomized rats. The resultswere characterized by a considerable diversity. In case ofbody weight reduction, estradiol’s benefit influence wasmuch better. In contrast, aortic cGMP and serum TC andpeNOS, NOX2, NOX4, and ROS generation in the aorta wereaffected in similar or even entirely the same way by bothagents. Additionally, in case of serum TG the plant materialsproved to possess much better ability to restore the valuesobserved in sham-operated control animals [115].

3.1. The Comparison of Crude Extracts and the ParticularSubstances Separated from Plant Materials. The plant extractcan show better properties than particular compoundsadministered alone as there may occur some synergisticeffects among its components. Such an assumption couldbe supported by the results reported by He et al. [148] whocompared the influence of Paeonia suffruticosa seed extractand 10 compounds (oligostilbenes) isolated from it withusing an in vitro IL-1β-induced osteoarthritis model. In thestudy performed on rabbit chondrocytes, IL-1β caused a sig-nificant decrease in viability and 10 studied components usedalone showed an improving effect, but the intensity of thiseffect was markedly different, depending on the structure.However, the application of the extract containing all the oli-gostilbenes showed the best effect, comparable with thatobserved for diacerein—a drug of IL-1β-inhibition action,used in osteoarthritis therapy. Such results made the authorssuggest the possibility of synergism among the particularoligostilbenes.

3.2. Plant Preparations as Lipid Profile Regulating Agents –The Comparison with Standard Drugs. Plan preparationswere studied in regard to the possibility of their application

36 Oxidative Medicine and Cellular Longevity

Table17:T

heprotective

effectsof

plantorigin

materialsin

anim

almod

elsof

obesity.

Reference

Plant

extract,do

se,w

ayandtimeof

treatm

ent,andanim

als

Indu

cing

factor

andnegative

effects

Protectiveeffectsof

plantmaterial

Effectsof

plant

perse

deOliveira

etal.[43]

Euterpeoleracea

Mart.(açaí)seed

hydroalcoh

olicextract

300mg/kg/d,i.g.,for12

weeks

MalemiceC57BL/6,4weeks

Diet-indu

cedobesity

60%

fatdietfor12

weeks

Epididymalandretrop

eriton

ealfat

mass↑

Bod

yweightgain↑

Liver/body

weight:↑

Glikaemia:↑

Plasm

a:adipon

ectin↓,leptin

↑Serum:T

C,T

G,L

DL,

VLD

L↑

Liver:SO

D,C

AT,G

Px↓,cholesterol,

TG,M

DA,P

C↑

Liverexpression

oflip

ogenicproteins:

pAMPK,p

ACC/A

CC↓,

SREBP-1c,HMG-C

oA-R

↑

Epididymalandretrop

eriton

ealfat

mass(++)

Bod

yweightgain

(++)

Liver/body

weight:(+++)

Glikaemia:(++)

Plasm

a:leptin,adipo

nectin

(+++)

Serum:T

C,T

G,L

DL,

VLD

L(++)

Liver:cholesterol,TG(++),SO

D,C

AT,G

Px,PC(+++),

MDA(↓),CAT(↑)

Liverexpression

oflip

ogenicproteins:p

AMPK,

SREBP-1c,HMG-C

oA-R,p

ACC/A

CC(+++)

Liver:TG↓,

SOD↑

Bud

riesietal.[133]

Castaneasativa

Mill

bark

extract

(ENC®,

SilvaT

eam

S.p.a.,San

Michele

Mon

dovì,Italy)

20mg/kg,p

.o.,for21

days

MaleSprague-Daw

leyrats,9-w

eek-

old,

270-300g

High-fatdietfor10

weeks

andthen

during

extractadministration

Bod

yweightgain:↑

Serum:T

C,L

DL-c,TG↑,HDL-c↓

Plasm

a:IL-1α,IL-1β

,IL-2,IL-5,IL-6,IL-7,

IL-12p70,IL-17A,IL-18,T

NF-α↑,

IL-4,IL-10,IL-13

↓Liver:SO

D,G

SSG-red,U

DPGT↓

Ileum:M

DA↑

Colon

:MDA↑

Bod

yweightgain:(++)

Serum:T

G(++),TC,L

DL-c,HDL-c(+++)

Plasm

a:IL-1β(-),IL-5,IL-18

(0),IL-7,T

NF-α(+),

IL-1α,IL-2,IL-6,IL-12pro70,IL-4,IL-10

(++),

IL-17A

,IL-13

(+++)

Liver:UDPGT(++),SO

D,G

SSG-red

(↑)

Ileum:M

DA(+++)

Colon

:MDA(++)

Liver:SO

D↑

Ileum:M

DA↑

ElA

yedetal.[132]

10%

ethano

lextractof

Vitisvinifera

grapeseed

(50%

)andskin

(50%

)500mg/kg

b.w.,i.p.,daily

for6weeks

MaleWistarrats,210–230

g

High-fatdiet(40%

fat,45%

carboh

ydrate,

15%

protein)

for6weeks

Bod

yandlung

weight:↑

Lung

lipid

content:↑

Plasm

a:adipon

ectin,

HDL-c↓,CRP,T

G,

TC,V

LDL-c,LD

L-c/HDL-c,LD

L-c↑

Lung:C

AT,SOD,Z

n,Mg↓,MDA,lipase,

Ca,Fe

↑

Bod

yandlung

weight:(+++)

Lung

lipid

content:(+++)

Plasm

a:CRPandadipon

ectin(++),TG,T

C,

VLD

L-c,LD

L-c,LD

L-c/HDL-c,HDL-c(+++)

Lung:M

DA(++),CAT,SOD,lipase,Mg,Zn,

Ca,Fe

(+++)

Plasm

a:TG,

TC,V

LDL-c,

LDL-c,HDL-c,

LDL-c/HDL-c

↓Lu

ng:Z

n↑,

MDA,M

g↓

Qiu

etal.[61]

Hedansanq

iTiaozhi

Tang(a

Chinese

herbalprescription

)contains

four

traditionalC

hinese

herbalmedicines:

Pana

xnotoginsengdryroot,Salvia

miltiorrhiza

Bun

gedryroot,C

rataegus

pinn

atifida

Bge.fruit,

Nelum

bonu

cifera

Gaertnleaf

350,700,1400

mg/kg/day,i.g.,

once

aday,for4weeks

MaleSprague-Daw

leyrats,180–190

g

Hyperlip

idaemiaindu

cedby

high-fat

diet

(2%

cholesterol,10%

lard,10%

eggyolk,0.5%

bilesodium

,77.5%

standard

diet(w

/w),for4weeks

Bod

yweight↑

Serum:T

C,T

G,L

DL-c,AST

,ALT

,MDA↑,

HDL-c,SO

D,C

AT,

GPx,T-A

OC↓

Liver:T-A

OC,SOD,C

ATandGPx↓,

TC,T

G,M

DA↑

Liver:steatosis,lobu

larinflam

mation,

hepatocellu

larballoon

ing↑

Bod

yweight:(+

350,++700and1400)

Serum:L

DL-c,TC,(+350,++700and1400),CAT(+

350,

+++700and1400),TG,G

Px(++350and700,+++1400),

T-A

OC,M

DA,SOD(++350,+++700and1400),

HDL-c,ALT

,AST

,(+++alld

oses)

Liver:MDA(+

350,+++700and1400),TC,T

G,

GPx(++350and700,+++1400),T-A

OC,C

AT

(++350,+++700and1400),SO

D(+++alld

oses)

Liver:steatosis(+

alld

oses),lobu

larinflam

mation

(++alld

oses),hepatocellu

larballoon

ing

(++350and700,+++1400)

4200

mg/kg

stud

ied:

none

37Oxidative Medicine and Cellular Longevity

Table17:C

ontinu

ed.

Reference

Plant

extract,do

se,w

ayandtimeof

treatm

ent,andanim

als

Indu

cing

factor

andnegative

effects

Protectiveeffectsof

plantmaterial

Effectsof

plant

perse

Shengetal.[33]

Morus

alba

var.multicaulis(Perrott.)

Loud

.(mulberry)

leaves

20%

mulberryleafpo

wderaddition

tohigh

fatdiet,13weeks

MaleC57BL/6J

mice,

4-week-old,

15-20g

Obesitycaused

byhigh

fatd

iet(60%calories

from

fat),providedbefore

(aroun

d8weeks)

anddu

ring

mulberryadministration

Bod

yweight,fatmass↑

BAT:bod

yweightratio↓

Fastingbloodglucoseandplasmainsulin

↑HOMA-IR↑

Serum:A

ST,C

R↑

Bod

yweight:(++beginn

ingfrom

6thweek

oftreatm

ent)

FatmassandBAT:bod

yweightratio(++),

fastingbloodglucoseandplasmainsulin

(++),HOMA-IR(+++)

Serum:A

ST,C

R(+++)

Not

stud

ied

↓:adecrease

vs.con

trol;↑:anincrease

vs.con

trol;(+):aslight

beneficialeffect;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect;(0):no

beneficialeffect;(-):intensification

oftheharm

fuleffect.

38 Oxidative Medicine and Cellular Longevity

Table18:T

heprotective

effectsof

plantorigin

materialsin

anim

almod

elsof

gastriculcers.

Reference

Plant

preparation,

dose,w

ay,tim

eof

treatm

ent,andanim

als

Indu

cing

factor

andnegative

effects

Protectiveeffectsof

plantpreparation

Effectsof

plantperse

Rtibi

etal.[135]

Ceratonia

siliqua

L.po

daqueou

sextract

Pretreatm

ent,500,1000,and

2000

mg/kg,b.w.,p.o.,

during

15days

MaleWistarrats,220–250

g

Ethanol

4g/kg,b.w.,p.o.,one

dose

Ulcer

index↑

Ulcer

mucus

volume↓

Stom

achmucosa:MDA,H

2O2↑,-SH

grou

ps,SOD,C

AT,G

Px↓

Ulcerindex:(++alldoses,a

decreasealon

gwithan

increaseddo

se)

Ulcer

mucus

volume:(++500and1000,+

++2000)

Stom

achmucosa:SO

D,C

AT(++500and1000,+

++2000);MDA

(++500and1000,+

++2000);H

2O2,-SH

grou

ps,G

Px

(0500,++1000,+

++2000)

Not

stud

ied

Chand

aetal.[45]

Paederia

foetidaL.

leafmethano

lextract

100,200mg/kg

b.w./d

ay,

for4days

Wistarrats,150-180

g

Indo

methacin-pylorusligation

indu

cedulcer

Indo

methacin25

mg/kg,s.c.,on

cedaily

for4days

+surgicalprocedure

onthe4thday

Gastricsecretion:

volume,acid

output

↑,pH

↓Ulcer

index:↑

Gastricsecretion:

volumeandacid

output

(++bo

thdo

ses),

pH(++100,+++200)

Ulcer

index:(++both

doses)

Not

stud

ied

Sabiuetal.[136]

Spondias

mom

binandFicus

exasperata

leafaqueou

sextracts

Pretreatm

ent

100or

200mg/kg

b.w.,

p.o.,for

21days

Wistarrats,about

180g

Indo

methacin-indu

cedgastric

ulceration

,asingledo

seof

30mg/kg

b.w.,p.o.

Ulcer

index:↑

Gastricsecretion:

acid

output

↑,pH

↓Stom

ach:

MDA↑,SO

D↓

Gastricjuice:pepsin

activity

↑,mucin

content↓

Ulcer

index:(++both

dosesof

both

extracts)

%ulcerinhibition

:(++both

dosesof

both

extracts)

Gastricsecretion:

acid

output

andpH

(++both

dosesof

both

extracts)

Ficusexasperata

Stom

ach:

MDA,SOD(++both

doses)

Gastricjuice:pepsin,m

ucin

(++both

doses)

Spondias

mom

bin

Stom

ach:

MDA,SOD(++both

doses)

Gastricjuice:pepsin,m

ucin

(++both

doses)

The

higher

dosesshow

edbetter

beneficialeffects

200mg/kg

b.w.only

stud

ied,

slight

effects

Gastricsecretion:

acid

output

↑,pH

↓Gastricjuice:mucin

content↓

Sattar

etal.[137]

Myristica

fragrans

seeds

70%

ethano

lextract

200mg/kg,anho

urbefore

ethano

l,on

ceadayfor15

days

Wistarrats,150-300

g

90%

ethano

l-indu

cedgastriculcers

5mL/kg

for15

days,onceaday

Gastriccontents:p

H↓,totalacidity

↑;averagenu

mberof

ulcers

peranim

al↑

Ulcer

index:↑

Gastriccontents:p

H↑,totalacidity

(++)

Average

numberof

ulcersperanim

al(++)

Ulcer

index:(++)

%ulcerinhibition

:(++)

Not

stud

ied

Raeesi

etal.[134]

Biebersteinia

multifida

root

70%

methano

lextract

Pretreatm

ent150or

300mg/kg,

p.o.,1

hbefore

ulcerindu

ction

MaleWistarrats,200-250

g

75%

ethano

l-indu

cedgastriculcer

4mL/kg,p

.o.

Ulcer

area/stomach↑;

Num

berof

ulcers/stomach↑;

Gastricmucosa:T-A

OC↓

Ulcer

area/stomach:

(+++both

doses)

Num

berof

ulcers/stomach:

(++both

doses)

Gastricmucosa:T-A

OC(↑

both

doses)

Not

stud

ied

↓:adecrease

vs.con

trol;↑:anincrease

vs.con

trol;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect.

39Oxidative Medicine and Cellular Longevity

Table19:T

heprotective

effectsof

plantorigin

materialsin

anim

almod

elsof

variou

sdiseases.

Reference

Plant

extract,do

se,w

ayandtimeof

treatm

ent,

andanim

als

Disorder,indu

cing

factor,and

negative

effects

Protectiveeffectsof

plantmaterial

Effectsof

plant

perse

Benhelim

aetal.[139]

Nigellasativa

L.seedsessentialo

il,5mL/kg

b.w.

from

1stto

28thor

from

15thto

28th

days,p

.o.

MaleWistarrats,120-130

g

Lithiasisindu

cedby

0.75%

ethylene

glycol

(EG)and1.0%

ammon

ium

chloride

indrinking

water

for28

days,first3

days

both,

then

onlyEG,for

25days

Bod

yweight:↓

Urine:M

g,Ca↓,oxalate,UA,p

hosphate↑

Serum:C

R,U

A,B

UN

↑Kidney:oxalate,Ca,ph

osph

ate↑

From

1stto

28th

Bod

yweight:(++)

Urine:C

a,Mg,oxalate,UA,p

hosphate(++)

Serum:C

R,U

A,B

UN

(++)

Kidney:oxalate,Ca,ph

osph

ate(++)

From

15stto

28th

Bod

yweight:(++)

Urine:C

a,Mg,oxalate,UA,p

hosphate(++)

Serum:C

R(+),UA,B

UN

(++)

Kidney:oxalate,Ca,ph

osph

ate(++)

The

latter

treatm

entshow

edworse

effects

Not

stud

ied

Chang

etal.[140]

Lycium

barbarum

fruitwater

extracts

Blend

ed:p

articles

3:58

±3:8

μm

Subm

icron:

particles100±

70nm

Dietary

pretreatment:250mg/kg

for54

days,p

.o.

MaleSprague-Daw

leyrats,8–10

week,200-300g

Retinaldegeneration

indu

cedby

whitecool

light,the

intensity1,400–1,500luxfor2

days,12hlight/12hdark

cycle

Retinalthickn

ess:↓

Retina:GSSG+GSH

↓,MDA↑

Subm

icronextract:retinalthickness

(++)

Retina:GSSG+GSH

↑,MDA(+++)

Blend

edextract:retinalthickness

(+)

Retina:GSSG+GSH

(++),MDA(+++)

Not

stud

ied

Cojocariu

etal.[141]

Chrysan

thellum

american

umpo

lyph

enolic

(butanol)fraction

of80%

ethano

licextract

100mg/kg

b.w.,i.g.,2days

during

and4days

afterstressparadigm

FemaleWistarratsabou

t200g

Irritablebowelsynd

romeanim

almod

elindu

cedby

multifactorialstressexpo

sure

paradigm

for7days

Tem

porallobe:SO

DandGPx↓,MDA↑

Tem

porallobe:SO

DandGPx,MDA(++)

Non

e

Sdayriaetal.[41]

Euphorbiaretusa

leafmethano

lextract

Pretreatm

ent200mg/kg,p

.o.

Swissalbino

mice,20–30g

Inflam

mation,

indu

cedby

1%carrageenan

(in0.9%

NaC

l)injectionof

100μLinto

the

subp

lantar

region

oftherighthind

paw

Hindpaw:M

DA↑,SO

D,C

AT,G

Px↓

Liver:SO

D,C

AT,G

Px↓

Hindpaw:M

DA,C

AT,G

Px,SO

D(++)

Liver:SO

D,C

AT,G

Px(++)

Not

stud

ied

Hatipoğlu

etal.[142]

Crataegus

orientalisM

Bieber.fruit70%

ethano

lextract

100mg/kg/day,orogastrically,atplacem

ent

oftheligature,for11

days

MaleWistarrats,aged4mon

ths,abou

t340g

Periodo

ntitiscaused

bysubm

erging

a4/0silk

ligaturein

thesulcus

ofthe

mandibu

larrightfirstmolarsof

rats,kept

subgingivally

foraperiod

of11

days

Serum:T

OS,OSI

↑,TAS↓

Interdentalareabetweenfirstandsecond

molars:inflam

matorycells,osteoclasts,

osteoblasts↑

Serum:T

OS,OSI,T

AS(+++)

Interdentalareabetweenfirstandsecond

molars:

osteob

lasts(0),inflam

matorycells

and

osteoclasts(++)

Not

stud

ied

40 Oxidative Medicine and Cellular Longevity

Table19:C

ontinu

ed.

Reference

Plant

extract,do

se,w

ayandtimeof

treatm

ent,

andanim

als

Disorder,indu

cing

factor,and

negative

effects

Protectiveeffectsof

plantmaterial

Effectsof

plant

perse

Kon

daetal.[138]

Azimatetracan

tharoot

95%

ethano

lextract

Pretreatm

ent250or

500mg/kg,p

.o.,60

min

priorto

glycerol

MaleWistaralbino

rats,150-250

g

Acuterenalfailure

caused

byhyperton

icglycerol,a

singledo

seof

8mL/kg,i.m

.,into

both

hind

limbs

Serum:C

R,B

UN

↑,TP,A

LB↓

Urine

output:↓

Kidney:SO

D,G

SH,G

R,G

Px,CAT↓

The

lower

dose:

Serum:T

P,C

R,B

UN,A

LB(++)

Urine

output:(++)

Kidney:GPx(0),CAT(+),SO

D,G

R(++),

GSH

(+++)

The

higher

dose:

Serum:T

P,A

LB(++),BUN,C

R,(+++)

Urine

output:(+++)

Kidney:SO

D,G

SH,G

R,G

Px,CAT(+++)

Only500mg/kg

stud

ied

Urinary

output:↑

Kidney:SO

D↓

Panth

etal.[36]

Salicorniaeuropaea

water

extract

1400

mg/kg/day

p.o.,for

6weeks

Malerats:spo

ntaneous

hypertensive

(SHR)rats

andSprague-Daw

ley,6weeks,about

200g

Vasculardysfun

ctionandhypertension

,NaC

l-indu

ced,

800mg/kg/day,p

.o.

for6weeks

SDrats:systolic

anddiastolic

pressure

↑SH

Rrats:systolic

anddiastolic

pressure

↑

SDrats:systolic

pressure

(+++),diastolic

pressure

(++)

SHRrats:systolic

pressure

(++),diastolic

pressure

(+)

Not

stud

ied

El-Kashlan

etal.[143]

Phoenixdactylifera

L.datepalm

pollen

(com

mercialprod

uct)

80%

ethano

lextract

150mg/kg,p

.o.,everydayfor56

days

MaleWistarrats,about

250g

L-thyroxine-indu

cedhyperthyroidism

300μg/kg,i.p.,everydayfor56

days

Weight:finalb

ody,testes,epididymis,

prostategland,

seminalvesicle↓

Serum:fT3,fT4,E2↑,LH

,FSH

,T,T

SH↓

Testis:SD

H,L

DH,A

LP,A

CP,G

6PD,C

AT,

SOD,G

Px,GR,G

SH↓,MDA,

NO,A

ST,A

LT↑

6-N-propyl-2-thiouracil-indu

ced

hypo

thyroidism

10mg/kg,i.p.,every

dayfor56

days

Weight:finalb

ody,testes,epididymis,

prostategland,

seminalvesicle↓

Serum:fT3,fT4,LH

,FSH

,T↓,E2,TSH

↑Testis:SD

H,L

DH,A

LP, A

CP,G

6PD,C

AT,

SOD,G

Px,GR,G

SH↓,MDA,

NO,A

ST,A

LT↑

Hyperthyroidism

Weight:finalb

ody,testes,epididymis,p

rostate

gland,

seminalvesicle(++)

Serum:fT3,TSH

,E2(++),fT4,LH

,FSH

,T(+++)

Testis:ALP

(++),SD

H,L

DH,A

CP,G

6PD,G

R,G

SH,

MDA,N

O,A

ST,A

LT,G

Px(+++),CAT,SOD↑

Hypothyroidism

Weight:finalb

ody,testes

(0),epididym

is,

prostategland,

seminalvesicle(++)

Serum:T

SH,fT3,fT4(0),E2(++),LH

,FSH

,T(+++)

Testis:ALP

,NO

(++),SD

H,L

DH,A

CP,G

6PD,G

R,

GSH

,MDA,A

ST,A

LT(+++),GPx,CAT,SOD

↑

Weight:prostate

gland,

epididym

is,

seminalvesicle↑

Serum:fT3,fT4↓

LH,T

,E2↑

Testis:SD

H,

LDH,G

R,C

AT,

SOD,G

Px,GSH

↑,MDA,N

O↓

You

etal.[144]

Ferm

entedpapaya

extracts(obtainedby

ferm

entation

ofpapaya

throughAspergillu

soryzae

for3mon

thsandthen

for3mon

thsusing

Saccharomyces

cerevisiae

yeasts)

30,15or

5mL/kg.p

.o.,days

1–30

FemaleSP

FSprague-Daw

leyrats,

180–200g,7-8weeks

Mam

maryglandhyperplasiaindu

cedby

estrogen

andprogestin,

0.5mg/kg

ofestradiolb

enzoate

Days1-25

and4mg/kg

ofprogestin

days

26–30,i.m

.Serum:E

2,progesterone,L

H,F

SH,M

DA,

AST

,totalbilirub

in↑;GPx,SO

D,A

LT↓

Liver:MDA↑;GPx,SO

D↓

Mam

marygland:

GPx,SO

D↓,

hyperplasia,MDA↑

Serum:M

DA(0

5,++15

and30),progesterone

(+5and

15,+

+30),totalb

ilirubin(0

5,++5,+++30),E2(++all

doses),LH(+

5,++5,+++30),FSH,A

LT,A

ST(++5and

15,+

++30);GPxandSO

D(0

5,+++15

and30)

Liver:MDA(0

5,++15

and30),GPx,SO

D(0

5,++15,+

++30)

Mam

marygland:

hyperplasia(0

5,+15,+

+30),MDA,

GPx(0

5,++15

and30),SO

D(0

5,+++15

and30)

Only30

mL/kg

stud

ied

Serum:SOD

↑Liver:SO

D↑

↓:adecrease

vs.con

trol;↑:anincrease

vs.con

trol;(+):aslight

beneficialeffect;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect;(0):no

beneficialeffect.

41Oxidative Medicine and Cellular Longevity

Table20:T

heprotective

effectsof

plantpreparations

againstradiation.

Reference

Plant

preparation,

dose,w

ayandtimeof

treatm

ent,anim

als

The

dose

andnegative

effects

Protectiveeffectsof

plantpreparation

Effectsof

plantper

se

Don

getal.[70]

Spatholobu

ssuberectus

Dun

n(Ji-Xue-TengBeijin

gLvye

Pharm

aceuticalC

o.Ltd.,C

hina)75%

ethano

lextract

40g/kg,p

.o.,for21

consecutivedays

afterirradiation

Chinese

Kun

Ming(K

M)mice,6–8weekaged

60Coγ-radiation,

ado

seof

6Gy

Bod

yweight:↓

Blood

:WBC,R

BC,P

LT,H

GB↓

Bon

emarrowtissue:B

cl-2

expression

,ph

osph

orylationof

JAK2andST

AT5a

↓Liver:ROS,MDA↑,SO

D,G

Px↓

Femur:bon

emarrowcells

↓

Bod

yweight:(+++)

Blood

:WBC,P

LT,H

GB(++),RBC(+++)

Bon

emarrowtissue:p

hospho

rylation

ofJA

K2(++),

phosph

orylationof

STAT5a

andBcl-2

expression

(+++)

Liver:ROS,MDA(++),SO

D,G

Px(+++)

Femur:bon

emarrowcells

(++)

Not

stud

ied

Jeenaetal.

[145]

Zingiberoffi

cina

leR(ginger)essentialo

il(K

ancore

IngredientsLimited,A

ngam

ali,Kerala,India)

100or

500mg/kg

b.w.p

.o.,5-daypretreatment

andthen

for14

days

MaleBalb/Cmice,6-8week

γ-Radiation

,6Gy,who

lebody

expo

sure

Blood

:WBC,H

GB↓

Intestinalmucosa:SO

D,C

AT,

GPx,GSH

↓

Blood

:WBC(++),HGB(+++)

Intestinalmucosa:SO

DCAT,G

PxandGSH

(++100,+++500)

Not

stud

ied

Khattab

etal.[146]

Boragooffi

cina

lisL.

seedsoil

Posttreatment:50

mg/kg

b.w./d

ay,p

.o.,3ho

urs

afterirradiationandfor2weeks

Pretreatm

ent:50

mg/kg

b.w./d

ay,p

.o.,on

eweekbefore

irradiationandfor2weeks

Malealbino

rats,160-180

g

γ-Radiation

asinglesublethald

oseof

6.5Gy

ofwho

lebody

Serum:G

SH,H

DL-c↓,AST

,ALT

,GGT,

MDA,T

G,T

C,L

DL-c↑

Liver:GSH

↓,MDA↑

Posttreatment:

Serum:A

ST,A

LT(++),GGT,M

DA,T

G,T

C,

GSH

,LDL-c,HDL-c(+++)

Liver:GSH

(++),MDA(+++)

Pretreatm

ent:

Serum:A

ST,A

LT(++),GGT,M

DA,T

G,T

C,

GSH

,LDL-c,HDL-c(+++)

Liver:GSH

(++),MDA(+++)

Non

e

Wang

etal.[147]

Rub

usidaeus

redraspberryethano

licextract

750μg/mLappliedon

thedo

rsalregion

ofthe

nude

mice1daybefore

UVBandthen

for5days

Femalenu

demice(ICR-Foxn/nu

strain)

UVB30

mJ/cm

2in

thedo

rsalregion

,on

ceadayfor5days

Totaldo

seof

150mJ/cm

2permou

seSkin

epidermalthickn

ess:↑

Transepidermalwater

loss↑

Erythem

a↑

Skin:C

OX-2,D

NAoxidationand

proteincarbon

ylation↑

Skin

epidermalthickn

ess:(+++)

Transepidermalwater

loss

(++)

Erythem

a(++)

Skin:C

OX-2,D

NAoxidation(++),protein

carbon

ylation(+++)

Not

stud

ied

↓:adecrease

vs.con

trol;↑:anincrease

vs.con

trol;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect.

42 Oxidative Medicine and Cellular Longevity

as lipid profile normalizing agents, and the results seem to beauspicious [120–122]. Additionally, the researchers per-formed comparisons with standard drugs. The outcomesshowed that the efficacy of plant material needs not be worsethan that showed by acknowledged pharmaceutical agents.However, it should be emphasized that the final effects maybe different, depending on the applied dose.

Veber et al. [34] compared the effects of two doses (125 or250mg/kg) of aqueous extract of red cabbage with thatshowed by fenofibrate, a drug used in therapy of abnormallipids in the blood, on oxidative stress parameters in rats withhyperlipidemia caused by Triton WR-1339. Although thehigher dose proved to possess protective properties generallycomparable with the drug, the lower one in some casesshowed no efficiency.

Erica multiflora L. leaf methanolic extract (150 or250mg/kg) effect was studied in rats with Triton WR-1339-induced hyperlipidemia in comparison with fenofibrate tak-ing into account chosen lipid and antioxidant parameters.The higher dose showed comparable or even better protectiveaction than the medicine. In contrast, total DNA damage wasalleviated much better by the used drug [120].

Onyenibe et al. [122] investigated the efficiency of twodoses of Monodora myristica aqueous extract as a protectiveagent in case of deterioration of lipid profile and oxidativeparameters in hypercholesterolemic rats and compared theobtained results with those noted for a standard drug Ques-tran. The authors found that generally two doses of plantpreparation, namely, 100 and 200mg/kg b.w., showed a bet-ter influence.

The effects of lipid-lowering drugs simvastatin and cipro-fibrate as well as aqueous extract of Campomanesia adaman-tium O. Berg root were compared in rats with high-fructosediet-induced hyperlipidemia. The plant material exerted theentirely comparable influence in case of lipid parametersand even better as regards body weight gain lowering [121].

3.3. The Comparison of Plant Extracts of HepatoprotectiveProperties with Pharmaceutical Agents. Liu et al. [51] com-pared the protective action of pretreatment with Sonneratiaapetala fruit water extract (100, 200, and 400mg/kg) againsthepatic damage caused by acetaminophen in mice with theeffect of an acknowledged antidote NAC (N-acetyl-L-cyste-ine). The scientists observed the protective influence of plantpreparation, which was not only comparable but in some casesbetter—particularly for serum ALT and AST as well as hepaticlipid peroxidation, antioxidant enzymes, TNF-α, and IL-6.

Similarly, the rich polyphenol fractions of methanolicextracts of Genista quadrifloraMunby and Teucrium poliumgeyriiMaire showed a protective effect against hepatoxicity ofacetaminophen (APAP) and the comparison with N-acetyl-cysteine showed their comparable properties with the drug,except for histological changes where Teucrium polium geyriiMaire exerted a better influence than two other studiedagents [20].

3.4. The Comparison of Plant Extracts with Silymarin, anAcknowledged Dietary Supplement of HepatoprotectiveProperties. Many drugs and chemicals are distinguished by

their hepatoxic effects. In view of the increasing environmen-tal pollution as well as more and more common applicationof different drugs, often over-the-counter ones, the protectiveagents are highly desirable [18]. Silymarin, a preparationobtained from Silybum marianum L., has been used as ahepatoprotective adjuvant for years. Currently, the attentionhas been pointed to other plants, often those used sinceantiquity in traditional medicine [44]. Different hepatotoxic-ity animal models were used to perform comparison withsilymarin.

The possibility of replacing silymarin by an extract ofCassia fistula L. leaves was studied by Kaur et al. [35] in ratsexposed to thioacetamide. The studied extract was applied atthree doses (50, 100, and 200mg/kg b.w.), and beneficialeffects of the two higher ones were not worse than thoseobserved in rats receiving silymarin.

The similar observations were reported by Fahmi et al.[53] who compared the protective properties of dietary gin-ger against diethylnitrosamine hepatotoxicity in rats withthose showed by silymarin and found that the studied mate-rial in the form of ginger powder or essential oil exerted thesame or even better beneficial action.

Choi et al. [46] studied the possibility of Centella asiaticaleaf ethanol extract (100 or 200mg/kg) using as a protectiveagent against dimethylnitrosamine-induced hepatotoxicityin rats. The authors determined different inflammatory cyto-kines and mediators, liver injury markers, oxidant parame-ters, and histophological changes. In some cases (liverhistology, serum IL-1β, TNF-α, and IL-2), both doses of theextract showed a better action than silymarin. In case ofAST, ALP, IL-6, and INF-γ or liver MDA, both agents dis-played the similarly significant properties. Furthermore, liverantioxidant enzymes were best ameliorated by the higherdose of plant preparation.

El-Hadary and Ramadan [52] in turn stated thatMoringaoleifera leaf extract displayed protective properties againsthepatotoxic action of diclofenac sodium. The comparisonwith silymarin proved that the plant preparation exertedcomparable or even better effect.

Ahmad and Zeb [18] in turn compared an effectiveness ofsilymarin and different doses of water extract of Trifoliumrepens leaves against acetaminophen-induced hepatoxicityin mice. The authors reported that in case of most studiedhematological, serum biochemical, and liver oxidativeparameters, the effect of the highest dose was not worse thanthat shown by silymarin.

However, the comparison of protective action of leafextract of Solanum surattense with that observed for sily-marin in CCl4-exposed rats revealed that the latter hadentirely better effect regarding liver injury markers and lipidprofile in serum as well as lipid peroxidation process in theliver [83].

On the other hand, Dogan and Anuk [44] observedthat in ethanol-exposed rats water extract of leaves ofPlatantus orientalis L. generally showed the protectiveeffects comparable or even better than those observed insilymarin-given animals. Interestingly, in case of someparameters, both silymarin and extracts showed insuffi-cient effectiveness.

43Oxidative Medicine and Cellular Longevity

The possibility of applying a plant extract as an adjuvantwhich could augment an action of an acknowledged agentwas also studied on an example of silymarin. Azim et al.[19] investigated effects of silymarin alone, Moringa pere-grina leaf extract alone, and coadministration of those sub-stances in rats subjected to acetaminophen. Generally, asregards plasma liver injury markers and oxidative parame-ters, the protective influence of all three treatments wasfound to be practically complete, but in some cases, the com-bination of both agents exerted the best effect. Interestingly,DNA damage was most markedly alleviated by plant extractalone while silymarin showed the slightest efficacy.

3.5. Immunosuppressive and Anti-Inflammatory Drugs vs.Plant Preparations. Pistacia weinmannifolia root extractwas compared regarding anti-inflammatory effects withroflumilast—a drug used in the therapy of lung inflammatorydisorders, in mice with pulmonary inflammation induced bycigarette smoke and lipopolysaccharide. The results of theexperiment showed that the studied preparation possessedprotective properties absolutely comparable with the appliedmedicine [149].

Sundaram et al. [55] studied the protective effect of gug-gulipid (an extract from Commiphora whighitii gum resin)against morphology changes, cartilage degradation, and pro-oxidative processes in rats with experimental arthritis. Alongwith the evaluation of the plant preparation properties, theauthors performed the comparison with a standard nonste-roidal anti-inflammatory drug ibuprofen. The influence ofthe studied extract proved to be comparable or even muchmore effective, particularly in cases of hematological andoxidative parameters.

In a study performed on mice subjected to 1-chloro-2,4-dinitrobenzene with the aim of inducing atopic dermatitis-like skin lesion, the effect of Rumex japonicus Houtt. rootextract was compared with the efficacy of a synthetic gluco-corticoid dexamethasone. The alleviation of the diseaseseverity caused by the topical application of the plant extractwas not much worse (particularly in the case of the higherdose) than that observed in animals treated intraperitoneallywith dexamethasone [77].

Kaveh et al. [117] in turn compared the influence of dif-ferent doses of hydroethanolic extract of Portulaca oleraceawith that exerted by dexamethasone in rats with experimen-tal asthma. According the authors, the effect of the highestdose (4mg/mL in drinking water) was comparable with thedrug. However, the lowest dose (1mg/mL in drinking water)in some cases showed no beneficial influence.

In some cases, the pharmaceutical agents showed a bettereffect. Sdayria et al. [41] reported that in mice withcarrageenan-induced paw edema pretreatment with a non-steroidal anti-inflammatory drug indomethacin or Euphor-bia retusa methanol extract showed comparable effectsconcerning % edema inhibition, although indomethacin dis-played a little better properties. However, in case of oxidantparameters in the liver and paw, the drug exerted more dis-tinct beneficial influence.

In the experiment performed by Jeong et al. [48], a non-steroidal anti-inflammatory drug celecoxib proved to be

much better in reversing the changes of biochemical param-eters observed in rats with monosodium iodoacetate-inducedosteoarthritis than a water extract of leaves of Morus alba L.Histological examinations confirmed the drug advantage.

3.6. Standard Drugs vs. Plant Preparations in Stomach UlcerAnimal Model. Sattar et al. [137] performed a comparisonof protective action of Myristica fragrans extract and sucral-fate (a drug used for stomach ulcer treatment) in rats withethanol-induced gastric ulcers. Although the plant prepara-tion was not so effective with regard to amelioration of totalacidity of stomach contents as well as macroscopic evaluationof gastric mucosa, ulcer index, and percentage of protection,its application did not cause serious increase in pH of stom-ach content as sulfacrate (4.25 vs. 5.0).

On the other hand, Biebersteinia multifida hydrometha-nolic extract showed a quite comparable or better protectiveeffect than another drug—namely, omeprazole—in cases ofgastric ulcers caused by 75% ethanol in rats. This effectincluded a decrease in ulcer area and number as well asenhancement of total antioxidant capacity in gastricmucosa [134].

Ateufack et al. [150] compared the effect of Piptadenias-trum africanum stem bark aqueous and methanol extracts(125, 250, or 500mg/kg) in rat gastric ulcer induced by theHCl/ethanol mixture, indomethacin, and acetic acid withthat showed by standard drugs (Maalox, Misoprostol, orRanitidine). Plant extracts, particularly aqueous one whenapplied in the highest dose, displayed the protective actioneven better than the investigated drugs in case of animalsexposed to HCl/ethanol mixture or indomethacin, but notin those treated with acetic acid.

Rtibi et al. [135] reported that in rats exposed to ethanol,pretreatment with Ceratonia siliqua L. aqueous extract (500,1000, and 2000mg/kg b.w.) showed a better or comparableeffect with the standard drug famotidine when applied atthe highest dose, while the lowest one was found to be eitherless effective or even ineffective at all.

The interesting results were reported by Chanda et al.[45]. The scientists studied the possibility of using Paederiafoetida Linn. leaf methanol extract (100 and 200mg/kgb.w.) as a gastroprotective agent in rats with gastric ulcersinduced by indomethacin-pylorus ligation, alcohol, or waterimmersion stress. The effects were compared with thoseobtained for standard drugs ranitidine, sucralfate, and lanso-prazole, respectively. As concerns ulcer protection, in the firstand third models, there were no distinct differences betweenthe plant material (particularly the higher dose) and theapplied drug. In contrast, in the second model, the higherdose of extract showed much better effectiveness than thelower one, but nonetheless not so high as sucralfate.

3.7. The Comparison of Plant Preparations withCytoprotective Adjuvants Used in Radio and Chemotherapy.The advantage of plant origin substances over drugs was alsoshown by Dong et al. [70]. Ethanol extract of JXT (a tradi-tional herb obtained from the Spatholobus suberectus Dunndry rattan) given orally to mice caused a significant improve-ment of the biochemical parameters previously disturbed by

44 Oxidative Medicine and Cellular Longevity

60Co γ-radiation, i.e., morphology, bone marrow cell num-ber, and liver lipid peroxidation level as well as activity ofantioxidant enzymes. This effect was comparable or betterthan that exerted by amifostine, an agent applied in cases ofradiation syndrome during radiotherapy.

3.8. Plant Preparations vs. Drugs and Supplements Applied inNeurological and Psychiatric Disorders. Pharmaceuticalagents used for the treatment of psychiatric and neurodegen-erative disorders may cause side effects worsening the condi-tion of patients. Plant preparations, often used for centuriesin traditional medicine, have been found to possess anxiolyticand antistress properties, and the comparison with acknowl-edged drugs and supplements showed their comparable effi-cacy [17, 58].

Plant materials, namely, extracts from two Hypericumspecies, were studied with regard to their effect on oxidativestress and inflammatory cytokines in an experimental anxi-ety animal model. The comparison with pure quercetin anda control drug alprazolam was also performed. In most cases,the disturbed brain parameters were positively influenced ina comparable or more distinct way by plant materials than bytwo other studied substances. It should be emphasized that insome cases the worst effect was observed in animals treatedwith alprazolam [17].

Almeida et al. [58] compared the protective effect ofClitoria ternatea extract with that shown by cotreatment withdietary supplements choline and docosahexanoic acidagainst brain oxidative stress caused by separation frommothers in rat pups. During 30-day experiment includingthe stressing factor and treatments as well as during the sub-sequent 330-day follow-up, both agents revealed comparableproperties regarding the prevention of lipid peroxidationincrease and thiol group content depletion.

Chonpathompikunlert et al. [31] compared the neuro-protective effect of Apium graveolens L. extract with thatshowed by a standard drug Tidomet Plus in an animal modelof Parkinson disease. The efficacy of two doses (250 and375mg/kg b.w.) proved to be quite comparable (the lowerone) or even better (the higher one) with the medicine asregards improvement of behavioral performance, oxidativeparameters, and activities of monoamine oxidases A and B.

3.9. Antidiabetic Drugs vs. Plant Preparations. The possibilityof plant preparations application in diabetic subjects was alsostudied. It was prompted by side effects occurring in patientstreated by pharmacological agents. The outcomes seem to bepromising although in view of the reported results the accu-rate research is needed to determine mechanism of actionand the most beneficial dose [66, 127].

Khanra et al. [129] stated that Abroma augusta L. leafmethanol extract (100 or 200mg/kg) was not so efficient atreversing the serum parameters disturbed in rats by type 2diabetes course, particularly in the case of the lower dose, asa standard drug glibenclamide. However, in the case of allevi-ating DNA fragmentation, ATP level, chosen oxidant param-eters, and expression of NF-κB in the kidney and heart, theprevalence of the drug was not so distinct.

The comparison of glibenclamide and methanolic extractof Caralluma europaea was performed by Dra et al. [127] ondiabetic mice. The higher dose of plant material (500mg/kgb.w.) was better effective in the reduction of blood glucosethan a drug, beginning from the 4th hour after administra-tion, while a lower one (250mg/kg b.w.) showed a compara-ble effect. Additionally, according to the authors, the lowerdose showed a more distinct beneficial influence in case ofhistopathological damage observed in diabetic animals.

The similar results were obtained by Du et al. [66] whocompared the protective properties of a standard drug met-formin hydrochloride and different doses (100, 250, and500mg/kg) of polysaccharide separated from Lycium bar-barum in the rat model of diabetes induced by high-fat diet+streptozotocin. Metformin showed a better effect in caseof fasting blood glucose and INF-α. As for insulin andICAM-1, the highest dose of plant origin material proved topossess better ameliorating properties, while serum GPxwas more improved by two higher doses.

Balbaa et al. [57] investigated the differences in effectsof administration of Nigella sativa seeds oil, standarddrugs metformin and glimepiride, and their combinationsto diabetic rats. The oil had a better protective actionwhen administrated alone than in combination withmetformin or glimepiride against oxidative stress and neu-roinflammatory cytokines’ increase. When the results ofadministration of those three agents alone to diabetic ratswere compared, the best properties of a plant materialwere also confirmed.

3.10. Plant Extract or a Single Substance of AntioxidantProperties? As beneficial effects of plant preparations wereattributed to their antioxidative properties, some researchesperformed the comparisons with simple substances ofacknowledged antioxidant character. The results showed thatplant materials could exert a better influence due to the pres-ence of many component which might cooperate with oneanother.

Jahan et al. [72] studied the possibility of application ofChenopodium album Linn. seed extract as a protective agentagainst the damage of reproductive functions caused by mer-cury exposure. They compared the effect of the plant extractwith that showed by a known antioxidant vitamin C whichwas reported to exert beneficial influence on male fertility.Except for plasma cholesterol and triglycerides as well asGST and TBARS in testicular tissue, the benefit influence ofthe studied plant material was comparable or even better.The similar observations were reported as regards the testic-ular morphometric parameters.

The comparison of the protective influence of Nigellasativa extract and vitamin E against cisplatin nephrotoxicitywas performed by Hosseinian et al. [16]. The cisplatin-induced negative changes, i.e., renal damage and thiol groupdecrease, and lipid peroxidation enhancement in the serumand kidney, were alleviated in a rather comparable way,except for serum thiols, where the prevalence of plant extractwas indisputable.

The effects of two Hypericum (H. maculatum and H.perforatum) species extracts on oxidative stress and

45Oxidative Medicine and Cellular Longevity

inflammatory cytokines were studied in an experimentalanxiety animal model and compared with pure quercetin.The beneficial influence of plant extracts was mostly compa-rable and in many cases better, particularly in the case ofHypericum maculatum [17]. Such results could point to syn-ergistic action of various components of extracts, acting asconfirmation of the conclusions made by He et al. [148].

3.11. The Action of a Plant Preparation Depending on ItsDose, Time and Form of Treatment

3.11.1. The Relationships between the Dose and the Effects. Inmany studies, the protective effects of plant extracts and con-stituents showed a direct dependency on the used dose [15,29, 31, 56, 80, 107, 117].

However, sometimes, the similar effects were observedfor a considerable wide range of the applied doses. Liu et al.[91] studied an effect of various doses (0.0625, 0.125, 0.25,0.5 g/kg b.w.) of ginseng oligopeptides against ethanol toxic-ity, and the observed differences were quite slight consideringthe size of the applied range.

Malik et al. [39] performed a study on animals with Hun-tington’s disease like symptoms and observed practically thesame influence of two different doses (100 and 200mg/kg) ofCelastrus paniculatus seed ethanol extract on memory func-tions, locomotor activity, and oxidative parameters in thebrain parts.

The relationships between used doses and an exertedinfluence were also studied in the experiment concerningthe protective properties of water extract of Sonneratia ape-tala fruit against liver damage caused by acetaminophenexposure in mice. The effects of pretreatment with differentdoses (100, 200 and 400mg/kg) were very interesting as inthe case of some parameters a strong dose dependency wasobserved (e.g., liver GSH and MDA), while some other oneswere affected in the same way, regardless of the applied dose(liver GSH, T-AOC, and TNF-α) [51].

In another study, Wang et al. [119] investigated the pro-tective properties of two doses (4.6 or 14 g/kg b.w.) of aque-ous extract of Salvia Miltiorrhiza Bge. f. alba in themonocrotaline-induced animal model of pulmonary hyper-tension. Various parameters were studied: mean pulmonaryartery pressure, right ventricular systolic pressure, pulmo-nary artery remodelling, plasma vasoactive factors NO, 6-Keto-PGF1α, ET-1, and TXB2, and lung TGF-β1, but theobserved differences were not as considerable as one couldexpect taking into account the difference between the applieddoses.

The similar observations were reported by El-Hadary andRamadan [52] who studied two doses ofMoringa oleifera leafextract (150 and 300mg/kg b.w.) against hepatotoxicity ofdiclofenac sodium. Both doses displayed protective proper-ties, but again, the difference between them was not so greatas one could predict considering their range.

Onyenibe et al. [122] studied the efficacy of two doses ofMonodora myristica aqueous extract at preventing impair-ment of lipid profile and oxidative parameters in hypercho-lesterolemic rats and generally found no difference between100mg/kg b.w. and 200mg/kg b.w.

Such results point to the necessity of complex research ofany possible protective agent with using a wide range ofdoses. The issue of dependency between the used dose andits effects proved to be additionally complicated as not alwaysa direct relationship was found. The effects of different doseswere sometimes divergent as in the experiment performed byKhan et al. [88], who studied the influence of two doses0.5 g/kg b.w. and 1.0 g/kg b.w. of ajwa dates (Phoenixdactylifera L.) water extract on the biochemical parametersin rats with diethylnitrosamine-induced liver cancer. Thelower one in some cases showed even a harmful effect (poten-tializing the changes caused by the carcinogen), while thehigher one showed considerable protective properties. Addi-tionally, the lower dose effect was characterized by a signifi-cant diversity as apart from showing the above-mentionedharmful influence, it also exerted a beneficial action, rangingfrom slight to strong.

In some cases, the higher dose had the worse effect than alower one. In the study performed by Omole et al. [26], con-cerning the possible use of pretreatment with kolaviron (amixture of flavonoids obtained from Garcinia kola seeds,200 or 400mg/kg/d) against toxicity of cyclophosphamide,the higher dose proved to be less beneficial, not only exertingless protective properties but also causing a slight increase inlipid peroxidation in the heart tissue.

The similar observations were reported by Apaydin Yil-dirim et al. [28] who studied the influence ofHelichrysum pli-catum DC. subsp. plicatum extract (100 or 200mg/(kg·d)against nephrotoxic as well as hepatotoxic effects of gentami-cin in rats. The authors stated that the higher dose showedmuch less beneficial influence. Additionally, the higher doseexerted some harmful effects, particularly regarding histopa-hological changes, when administered alone.

In some studies, it would be really very difficult to decidewhich dose should be chosen for usage. In the experimentperformed by Wattanathorn et al. [42], the beneficial influ-ence of the combination of extracts of Mangifera indica L.and Polygonum odoratum L. against diabetes cataract andretinopathy was distinctly showed, but the effect of differentdoses (2, 10, or 50mg/kg b.w.) was found to be highly diverse.

Phunchago et al. [92] studied the possible protectiveeffect of Tiliacora triandra water extract against ethanol-induced hippocampus damage in rats. The authors com-pared three doses: 100, 200, and 400mg/kg b.w., and foundthat the middle one showed the best influence in improvingsome studied parameters while in few cases the worst influ-ence was found for the highest one.

3.11.2. The Relationships between the Period of Treatmentand the Effects. The period of the treatment with the studiedsubstances also proved to be a factor of importance. Xu et al.[60] investigated the effect of Rhubarb extract on the oxida-tive parameters in rats with traumatic brain injury. Accord-ing to the reported results, the degree of improvement inlipid peroxidation intensity as well as antioxidants levelsshowed a dependency on the time of experiment. The ani-mals sacrificed after a longer period, starting from surgeryand plant material treatment, showed a better ameliorationof the studied parameters.

46 Oxidative Medicine and Cellular Longevity

3.11.3. The Relationships between the Way of Preparing PlantMaterials and Their Effects. As plant extracts contain manyactive substances of different solubilities in various solvents,the way of the preparation of the used substances also provedto be an issue of importance.

Malik et al. [39] studied the fractions of Celastruspaniculatus seed ethanol extract, obtained by suspendingit in water and sequential partitioning with using petro-leum ether, ethyl acetate and n-butanol. These materialswere investigated as to their ability to ameliorate the neu-rotoxic effect of 3-nitropropionic acid by reversing changesof oxidative parameters in striatum and cortex of experi-mental rats. In the case of improvement of enhancedMDA and nitrites as well as decreased CAT, SOD, andGSH, ethanol extract and aqueous fraction proved to bethe most effective; the petroleum ether fraction showedmuch less efficacy while n-butanol and ethyl acetate onespractically none.

3.11.4. Treatment of Pretreatment? The way of treatment, i.e.,pre or post, in some cases was shown to be a crucial factorinfluencing the observed effect to a considerable degree.Afsar et al. [23] studied the effects of ethyl acetate fractionof Acacia hydaspica methanol extract against cisplatin toxic-ity and observed that the protective influence observed in thecase of posttreatment started concomitantly with cisplatinand continued for five days was decidedly less distinct thanthat of 15-day pretreatment combined with posttreatment.

On the other hand, some authors did not report anydifferences between the mentioned two ways. Khattab et al.[146] did not observe any differences between pre- and post-treatment with Borago officinal L. seed oil in rats exposed toγ-radiation.

The similar effects were observed by Nasri et al. [109]in rats subjected to a contrast medium iodixanol and 70%ethanol green tea extract. The plant agent alleviatediodixanol-induced histopathological kidney changes, butno significant differences between pre- and posttreatmentwere observed.

Hosseinian et al. [16] studied the possible protectiveeffect against cisplatin nephrotoxicity ofNigella sativa extract(100 and 200mg/kg) using the design, whereby two ways ofadministration were applied—pretreatment alone or withthe addition of posttreatment. The outcomes were reallyinteresting. In case of renal SH groups and tissue damage aswell as serum SH groups and MDA plant material provedto possess beneficial effect, regardless of the way ofadministration.

4. The Effects of Plant Preparations Per Se

The fact that generally effects of plant preparations per sewere observed occasionally makes the considerable limitationof the studies presented in the current review. Only a few sci-entists reported observations considering any influence of thestudied materials. Sheweita et al., for instance, investigatedthe effects of application of essential oils of Foeniculumvulgare (fennel) Miller seeds, Cuminum cyminum L. (cumin)seeds, and Syzygium aromaticum L. (clove) flower and

reported that the used oils themselves caused several benefi-cial effects like decrease in liver TBARS as well as enhance-ment of liver antioxidants [101].

El-Kashlan et al. [143] found the decrease in lipid perox-idation as well as reinforcement of antioxidant defence in ratsreceiving commercial date palm pollen.

El-Rahman et al. [110] reported alleviation of prooxida-tive processes as well as the increase in antioxidants in ratsgiven Saussurea lappa root extract.

Furthermore, the beneficial influence of plant prepara-tions included not only improvement in biochemical param-eters. Sheng et al. [33] reported that, apart from positiveeffect on body and adipose tissue weight and insulin sensitiv-ity, liver, and kidney functions, addition of mulberry leavespowder to diet also caused amelioration of microbiota com-munity structure in gut of obese mice.

Balbaa et al. [57] investigated the differences in theeffects of administration of Nigella sativa seeds oil, antidia-betic drugs metformin and glimepiride, and their combina-tions to rats. In some cases, the plant oil per se showed theleast or no negative effect in nondiabetic rats when com-pared to medicines. The reduction of brain β-amyloid-42as well as the increase in antioxidants’ level was observed.On the other hand, brain lipid peroxidation was found tobe enhanced.

However, some authors reported the negative effects ofplant preparations on experimental animal organisms.

Apaydin Yildirim et al. [28] observed histopathologicalchanges in organs of animals treated with Helichrysum plica-tum DC. subsp. plicatum extract.

In one of the recently published articles, Nahdi et al.[151] observed that leaf Hypericum humifusum aqueous(200 or 400mg/kg b.w.) and methanolic (10 or 20mg/kgb.w.) extracts, given to rats, induced histopathologicalchanges as well as impaired biochemical parameters includ-ing an increase in WBC, liver MDA, plasma ALT, AST, andLDH. Additionally, activities of hepatic antioxidant enzymesCAT and SOD were markedly decreased vs. control with notreatment. Interestingly, in case of the aqueous extract, theworse effect was exerted by the lower dose while the metha-nolic one was found to be more harmful when given in thehigher dose.

5. Conclusions

The outcomes of the studies presented in the currentreview showed a huge potential inherent in plant prepara-tions. They were revealed to reverse or alleviate toxicity ofdifferent factors, side effects of drugs, and symptoms ofvarious diseases. In many cases, they were proved to becomparable or better than standard drugs which let us sug-gest that in future the plant origin substances could make areplacement for pharmaceutical agents. However, the pre-sented above results of some experiments point to the factthat the proper precautions must be undertaken beforeapplying any plant material. The detailed research regard-ing the per se effects, dose, and way of administrationneeds to be performed.

47Oxidative Medicine and Cellular Longevity

Abbreviations

AA: Ascorbic acidAβ: β-Amyloid peptideABCG: ATP-biding cassette, subfamily G

transportersACC: Acetyl-CoA carboxylaseAChE: Acetylcholine esteraseACP: Acid phosphataseADA: Adenosine deaminase activityAGE: Advanced glycation end productAGGRECAN: Cartilage-specific proteoglycan core proteinALB: AlbuminAlCl3: Aluminium chlorideALP: Alkaline phosphataseALT: Alanine aminotransferaseAOPP: Advanced oxidation protein productsAR: Aldose reductaseARE: Antioxidant-responsive elementAST: Aspartate aminotransferaseATP: Adenosine triphosphateBALF: Bronchoalveolar lavage fluidBAP: Biological antioxidant powerBAT: Brown adipose tissueBcl-2: B-cell lymphoma 2BMP2: Bone morphogenetic protein 2BUN: Blood urea nitrogenb.w.: Body weightCa: CalciumCa2+ATPase: Calcium-activated adenosine 5′

-triphosphataseCAT: CatalaseCCl4: Tetrachlorometan (carbon tetrachloride)Cd: CadmiumCd36: Cluster of differentiation 36cGMP: Cyclic guanosine-3′,5′-monophosphateChAT: Choline acetyltransferaseCHOP: C/EBP homologous proteinCK-MB: Creatinine kinase-MBCOL2: Collagen type-IICOL10: Collagen type 10COMP: Cartilage oligomeric matrix proteinCOX-2: Cyclooxygenase-2CR: CreatinineCRP: C-reactive proteinCS: Citrate synthasecTnI: Cardiac troponin ICTX-II: C-telopeptide of type II collagenCu: CopperCYP2E1: Cytochrome P450-2E1DBP: Diastolic blood pressureDC: Diene conjugateDHEAs: Dehydroepiandrosterone sulfateDNA: Deoxyribonucleic acidE2: EstradioleNOS: Endothelial nitric oxide synthaseERK1/2: Extracellular signal-regulated kinase 1 and 2ET-1: Endothelin-1

Fatp4: Fatty acid transport protein 4Fe: IronFFA: Free fatty acidsFRAP: Ferric reducing ability of plasmaFSH: Follicle-stimulating hormonefT3: Free T3fT4: Free T4γ-GCS: γ-Glutamyl cysteine synthetaseGGT: γ-Glutamyl transferaseGM-CSF: Granulocyte-macrophage colony-

stimulating factorG6PD: Glucose-6-phosphate dehydrogenaseGPx: Glutathione peroxidaseGR: Glutathione reductaseGRP78: 78 kDa glucose-regulated proteinGSH: Reduced glutathioneGSSG: The oxidized form of glutathioneGSSG-red: Oxidized glutathione reductaseGSSP: Glutationylated proteinsGST: Glutathione-S-transferaseHA: HyaluronidaseHbA1c: Glycated hemoglobinHCT: HaematocritHDL: High-density lipoproteinHDL-c: High-density lipoprotein cholesterolHg: MercuryHGB: HaemoglobinHMG-CoA-R: 3-Hydroxy-3-methylglutaryl CoA

reductaseHNE: 4-Hydroxy-2-nonenalHO-1: Heme oxygenase 1H2O2: Hydrogen peroxideHOMA-IR: Homeostasis model assessment-insulin

resistanceICAM-1: Intercellular adhesion moleculei.c.v.: IntracerebroventricularIDE: Insulin degradation enzymeIFN-α: Interferon-αIFN-γ: Interferon-γi.g.: IntragastricallyIgG: Immunoglobulina GIgM: Immunoglobulina MIL: Interleukini.m.: IntramuscularlyiNOS: Inducible nitric oxide synthasei.p.: Intraperitoneallyi.v.: IntravenouslyJAK: Janus kinaseK: PotassiumKEAP1: Kelch-like ECH-associated protein 16-Keto-PGF1α: 6-Keto-prostaglandin F1 alphaLDH: Lactate dehydrogenaseLDL: Low-density lipoproteinLDL-c: Low-density lipoprotein cholesterolLH: Luteinizing hormoneLpl: Lipoprotein lipaseLPO: Lipid peroxidationLPS: Lipopolysaccharide

48 Oxidative Medicine and Cellular Longevity

MAO-A: Monoamine oxidase type BMAO-B: Monoamine oxidase type BMCP-1: Monocyte chemoattractant protein 1M-CSF: Macrophage colony-stimulating factorMDA: MalondialdehydeMDSCs: Myeloid suppressor cellsMg: MagnesiumMg2+ATPase: Magnesium-activated adenosine 5′

-triphosphataseMIP: Macrophage inflammatory proteinMMP-1: Matrix metalloproteinase-1, interstitial

collagenaseMMP-3: Matrix metalloproteinase-3, stromelysin-1MMP-13: Matrix metalloproteinase-13, collagenase 3MMP: Matrix metalloproteinaseMPO: MyeloperoxidasemRNA: Messenger ribonucleic acidMT: MetallothioneinMTH 1: A gene encoding 8-oxo-7,8-dihydrodeoxy-

guanosine triphosphataseNa: SodiumNADH: Nicotinamide adenine dinucleotide

reduced formNa+/K+ATPase: Sodium- and potassium-activated adeno-

sine 5′-triphosphataseNASH: Nonalcoholic steatohepatitisNF-κB: Nuclear factor-kappa BNO: Nitric oxideNO3: NitrateNO2: NitriteNOX: NADPH oxidaseNP-SH: Nonprotein sulfhydryl groupsNQO1: NAD(P)H:quinone oxidoreductase 1Nrf2: Nuclear erythroid 2-related factor 28-OHdG: 8-Hydroxy-2′deoxyguanosineOSI: Oxidative stress indexP: PhosphorusP53: p53 proteinpACC: Phosphorylated acetyl-CoA carboxylasepAMPK: Phosphorilated adenosine-

monophosphate-activated protein kinasePb: LeadPC: Protein carbonylsPCG: Protein carbonyl groupsPCNA: Proliferating cell nuclear antigenpeNOS: Phosphorylated eNOSPGE2: Prostaglandin E2PGI2: ProstacyclinPHGPx: Phospholipid hydroxyperoxide GPxPKC: Protein kinase CPLT: PlateletsP38 MAPK: p38 mitogen-activated protein kinasepNF-κB: Phospho-NF-κBp.o.: OrallyQR: Quinone reductaseRANTES: Regulated on Activation, Normal T-cell

Expressed and SecretedRBC: Red blood cells

ROS: Reactive oxygen speciesSBP: Systolic blood pressures.c.: SubcutaneouslySDH: Sorbitol dehydrogenaseSH: Thiol groupsSHBG: Sex hormone-binding globulinSOD: Superoxide dismutaseSPF: Specific pathogen freeSrebf1: Sterol regulatory element-binding tran-

scription factor 1SREBP-1c: Sterol-regulatory-element binding protein-

1cSTAT: Signal transducer and activator of

transcriptionT: TestosteroneT-AOC: Total antioxidant capacityTAS: Total antioxidant statusTBARS: Thiobarbituric acid reactive substancesTC: Total cholesterolTG: TriglyceridesTGF-β: Transforming growth factor betatHcy: Total homocysteineTIMP: Tissue inhibitor of metalloproteinasesTLC: Total leukocytic countTLR: Tall-like receptorTNF-α: Tumor necrosis factor alphaTOS: Total oxidant statusTP: Total proteinTSH: Thyroid-stimulating hormoneTXA2: Thromboxane A2TXB2: Thromboxane B2UA: Uric acidUDPGT: UDP-glucuronosyl transferaseVEGF: Vascular endothelial growth factorVLDL: Very low-density lipoproteinVLDL-c: Very low-density lipoprotein cholesterolWBC: White blood cellsXO: Xanthine oxidaseZn: Zinc.

Conflicts of Interest

The authors declare that there is no conflict of interestregarding the publication of this article.

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