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Indian Journal of Natural Products and Resources Vol. 1(4), December 2010, pp.397-408 Herbs as liver savers- A review G D Chaudhary*, P Kamboj, I Singh and A N Kalia Department of Pharmacognosy, I.S.F. College of Pharmacy, Moga -142 001, Punjab, India Received 21 January 2010; Accepted 20 September 2010 Herbal medicines are in great demand in the developed world for primary health care due their efficacy, safety and lesser side effects. Recently, considerable attention has been paid to utilize eco-friendly and bio-friendly plant-based products. The current availability of high-tech methods allows researchers to optimize the effectiveness, standardization and clinical testing of these herbs to meet international standards. A wide group of medicinal plants and preparations had been used over centuries almost exclusively as antimicrobial, cytotoxic, antidiabetic, antiinflammatory, etc. In addition, numerous plants and polyherbal formulations are used in treatment of liver related disorders. However, for developing satisfactory herbal combinations to treat liver diseases plants needs to be evaluated systematically for its potency as antiviral, antihepatotoxicity, antioxidants, stimulation of hepatocytes regeneration and choleretic activity. Development and scientific studies have validated such herbal medicines or combinations confirming the biological efficacy and safety which revitalize treatment of liver disorders. The present review is systematically conducted to overview the plants like Andrographis paniculata Nees., Eclipta alba Hassk., Lawsonia alba Lam., Picrorhiza kurroa Royle ex Benth., and Silybum marianum Linn., proved as hepatoprotective and used as the ingredients of liver protection drugs in the last few decades. Nevertheless, much additional work is needed to open up new biomedical application of these plants. Keywords: Antioxidant, Herbs, Hepatoprotective, Hepatotoxic, Liver disorders, Serum transaminases IPC code; Int. cl. 8 —A61K 36/00, A61P 1/16 Introduction Medicinal plants play a key role in the human health care system. About 80% of the world population rely on traditional medicine which is predominantly based on plant materials 1 . The traditional medicine refers to a broad range of ancient, natural health care practices including folk/tribal practices as well as Ayurveda, Siddha and Unani. It is estimated that about 7,500 plants are used in health traditions in, mostly, rural and tribal villages of India. Out of these, the real medicinal value of over 4,000 plants is either little known or unknown to the mainstream population 2 . Health and well-being has been a subject of man’s primary concern since time immemorial. There has been resurgence of scientific interest in medicinal plants during the past few decades due to their importance in traditional system of medicine. Herbal medicines are in great demand in the developed world for primary health care because of their efficacy, safety and lesser side effects. A detailed investigation and documentation of plants used in health traditions and pharmacological evaluation of these plants and their taxonomical relatives can lead to the development of invaluable plant based drugs for many dreaded diseases. A large number of plants and purified natural substances have been screened for liver disorders 3 . Liver diseases are mainly caused by toxic chemicals, excess consumption of alcohol, infections and autoimmune disorder. Most of the hepatotoxic chemicals damage liver cells mainly by lipid peroxidation and other oxidative damages 4, 5 . Liver is the most important organ where drugs are structurally altered; resulting biologically inactive or active metabolites and some of these are toxic. Liver is exposed to drugs in higher concentration as whole of the drug pass through liver to reach systemic circulation. Thus, the liver is a vulnerable target of injury from various chemicals and drugs and disordered hepatic function is an important cause of abnormal drug handling 6 . Further liver has capacity to recover from acute injury by hepatocellular regeneration with the production of new cells, which restore liver functions and normal tissue structure. Chronic liver injury, however often leads to fibrosis, scar formation and distortion of normal tissue architecture 7 . —————— *Correspondent author E-mail: [email protected] Phone: 01636-236564, 09463509193(Mob.) Fax No. 01636-236564

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Page 1: Herbs as liver savers- A review - NISCAIRnopr.niscair.res.in/bitstream/123456789/10824/1/IJNPR 1(4) 397-408.pdf · Indian Journal of Natural Products and Resources Vol. 1(4), December

Indian Journal of Natural Products and Resources

Vol. 1(4), December 2010, pp.397-408

Herbs as liver savers- A review

G D Chaudhary*, P Kamboj, I Singh and A N Kalia

Department of Pharmacognosy, I.S.F. College of Pharmacy, Moga -142 001, Punjab, India

Received 21 January 2010; Accepted 20 September 2010

Herbal medicines are in great demand in the developed world for primary health care due their efficacy, safety and lesser

side effects. Recently, considerable attention has been paid to utilize eco-friendly and bio-friendly plant-based products. The

current availability of high-tech methods allows researchers to optimize the effectiveness, standardization and clinical

testing of these herbs to meet international standards. A wide group of medicinal plants and preparations had been used over

centuries almost exclusively as antimicrobial, cytotoxic, antidiabetic, antiinflammatory, etc. In addition, numerous plants

and polyherbal formulations are used in treatment of liver related disorders. However, for developing satisfactory herbal

combinations to treat liver diseases plants needs to be evaluated systematically for its potency as antiviral,

antihepatotoxicity, antioxidants, stimulation of hepatocytes regeneration and choleretic activity. Development and scientific

studies have validated such herbal medicines or combinations confirming the biological efficacy and safety which revitalize

treatment of liver disorders. The present review is systematically conducted to overview the plants like Andrographis

paniculata Nees., Eclipta alba Hassk., Lawsonia alba Lam., Picrorhiza kurroa Royle ex Benth., and Silybum marianum

Linn., proved as hepatoprotective and used as the ingredients of liver protection drugs in the last few decades. Nevertheless,

much additional work is needed to open up new biomedical application of these plants.

Keywords: Antioxidant, Herbs, Hepatoprotective, Hepatotoxic, Liver disorders, Serum transaminases

IPC code; Int. cl.8—A61K 36/00, A61P 1/16

Introduction Medicinal plants play a key role in the human

health care system. About 80% of the world

population rely on traditional medicine which is

predominantly based on plant materials1. The

traditional medicine refers to a broad range of ancient,

natural health care practices including folk/tribal

practices as well as Ayurveda, Siddha and Unani. It is

estimated that about 7,500 plants are used in health

traditions in, mostly, rural and tribal villages of India.

Out of these, the real medicinal value of over 4,000

plants is either little known or unknown to the

mainstream population2. Health and well-being has

been a subject of man’s primary concern since time

immemorial. There has been resurgence of scientific

interest in medicinal plants during the past few

decades due to their importance in traditional system

of medicine. Herbal medicines are in great demand in

the developed world for primary health care because

of their efficacy, safety and lesser side effects. A

detailed investigation and documentation of plants

used in health traditions and pharmacological

evaluation of these plants and their taxonomical

relatives can lead to the development of invaluable

plant based drugs for many dreaded diseases. A large

number of plants and purified natural substances have

been screened for liver disorders3.

Liver diseases are mainly caused by toxic chemicals,

excess consumption of alcohol, infections and

autoimmune disorder. Most of the hepatotoxic

chemicals damage liver cells mainly by lipid

peroxidation and other oxidative damages4, 5

. Liver is the

most important organ where drugs are structurally

altered; resulting biologically inactive or active

metabolites and some of these are toxic. Liver is

exposed to drugs in higher concentration as whole of the

drug pass through liver to reach systemic circulation.

Thus, the liver is a vulnerable target of injury from

various chemicals and drugs and disordered hepatic

function is an important cause of abnormal drug

handling6. Further liver has capacity to recover from

acute injury by hepatocellular regeneration with the

production of new cells, which restore liver functions

and normal tissue structure. Chronic liver injury,

however often leads to fibrosis, scar formation and

distortion of normal tissue architecture7.

——————

*Correspondent author

E-mail: [email protected]

Phone: 01636-236564, 09463509193(Mob.)

Fax No. 01636-236564

Page 2: Herbs as liver savers- A review - NISCAIRnopr.niscair.res.in/bitstream/123456789/10824/1/IJNPR 1(4) 397-408.pdf · Indian Journal of Natural Products and Resources Vol. 1(4), December

INDIAN J NAT PROD RESOUR, DECEMBER 2010

398

Supporters of herbal medicine claim that herbs may

treat and prevent diseases. This adds to a deep belief

that these treatments are safe as they are natural and

fit into the image of a gentle and therefore, harmless

alternative to conventional medicine. Herbal remedies

support natural healing phenomena through blocking

the progression of the degenerative pathological

processes. Modern medicine offers limited success in

providing effective cure and there is a severe need to

develop new drugs capable of healing toxic liver

damages. In traditional systems of medicine, plants

were claimed to be effective and used successfully to

alleviate multiple liver disorder8. But, evidence for

efficacy is sparse. In spite of limitations, a number of

herbal show promising effects, either experimentally

in cell culture (in-vitro models), animal studies (in-vivo

models), or even in clinical trials.

In this regards, we systematically summarized

reported scientific papers that describe evaluations of

liver protective plants and critically appraised the

evidence based as par to international standards for

appropriate scientific study designs that could justify

their use as hepatoprotective agents. Clinically tested plants

Silybum marianum Linn. (Fam.-Asteraceae) has

been used to treat liver diseases since 16th century.

Major constituents of plant are flavonoids (silibinin,

silidianin, silichristin and isosilibinin). Silibinin is the

biologically most active compound. The pharmaco-

logical profile of silymarin has been well defined and

hepatoprotective properties of silymarin were

investigated both in-vitro and in-vivo models.

Experimental studies demonstrated its antioxidant,

free radical scavenging properties and improvement

of the antioxidative defence by preventing glutathione

(GSH) depletion and antifibrotic activity9.

Pharmacologically tested plants

Aqueous extract of leaves of Adhatoda vasica

Nees (Fam.-Acanthaceae), showed significant

hepatoprotective effect at doses of 50-100mg/kg, p.o.

on liver damage induced by D(+) galactosamine

(D(+)GalN) (200mg/kg, i.p.) in Wistar rats (either sex).

The extract possessed a potent antioxidant effect10

.

Aqueous extract of Aloe barbadensis Mill. (Fam.-

Liliaceae) aerial parts at dose of 500mg/kg, p.o. was

significantly capable of restoring integrity of

hepatocytes indicated by improvement in physiological

parameters, excretory capacity of hepatocytes and

also by stimulation of bile flow secretion in

male Wistar rats or Swiss Albino mice. Extract

prevented the hepatic damage against carbon

tetrachloride (CCl4) (1ml/kg, p.o.) and significantly

ameliorated the levels of aspartate transaminase

(AST), alanine transaminase (ALT) and alkaline

phosphatase (ALP)11

.

Methanol seeds extract (250mg/kg, p.o.) of Apium

graveolens Linn. (Fam.-Apiaceae) and aerial parts

(200mg/kg, p.o.) of Croton oblongifolium Roxb.

(Fam.-Euphorbiaceae) showed significant

hepatoprotective activity against CCl4 (1.5ml/kg, p.o.)

induced hepatotoxicity in female Albino Wistar rats12

.

Fresh juice of tender leaves of Azadirachta indica

A. Juss. (Meliaceae) (200mg/kg, p.o.) inhibited

acetaminophen (APAP) (2g/kg, p.o.) induced lipid

peroxidation and prevented depletion of sulfhydryl

groups in liver cells of Albino rats (CF strain) of

either sex. Pre-treatment with juice stabilized the

significant increased serum enzyme levels13

.

Aqueous extract (100mg/kg, p.o.) of aerial parts of

Ballota glandulosissima Hub.-Mor & Patzak.

(Lamiaceae) showed hepatoprotective effect against

CCl4 (0.8ml/kg, i.p.) induced hepatotoxicity in either

sex of Sprague-Dawley rats and Swiss Albino mice.

Treatment with plant extract significantly ameliorates

the levels of serum maker enzymes elevated by

the toxicant14

.

Latex of Calotropis procera Ait. (Asclepiadaecae)

was evaluated for its hepatoprotective effect against

CCl4 (2ml/kg, s.c., in olive oil) induced hepatotoxicity

in Wistar rats of either sex. Oral administration of

aqueous suspension of dried latex at 5, 50 and

100mg/kg doses produced a dose-dependent reduction

in the serum levels of liver enzymes. The dried latex

treatment also normalized various biochemical

parameters of oxidative stress15

. Ethanol and aqueous extracts (250mg/kg, p.o.) of

dried fruits of Carica papaya Linn. (Caricaceae) showed remarkable hepatoprotective activity against CCl4 (1.25ml/kg, p.o.) induced hepatotoxicity in male Albino rats. Decrease in serum bilirubin after treatment with the extract in toxicated group indicated the effectiveness of the extract in normal functional status of the liver. So, the result indicates that the ethanol and aqueous extracts of C. papaya possess significant hepatoprotective activity

16.

Treatment with aqueous leaves extract (250 and 500mg/kg, i.g.) of Cassia auriculata Linn. (Caesalpiniaceae) to ethanol (5ml/kg, 20%, i.g.) intoxicated male Wistar rats showed hepatoprotective effect when compared to unsupplemented ethanol

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CHAUDHARY et al: HERBS AS LIVER SAVERS– A REVIEW

399

intoxicated rats. Treatment with extract elevated the activities of superoxide dismutase (SOD) and catalase (CAT) and significantly lowered the levels of thiobarbituric acid reactive substances (TBARS), hydroperoxides, also reduced the levels of total bilirubin (TB), AST, ALT, ALP in serum and GSH in the liver

17.

The effect of 50% ethanol extract (400mg/kg, p.o.)

of Chamomile (Matricaria chamomilla Linn.)

(Asteraceae) capitula flowers on blood and liver GSH,

sodium potassium adenosine tri-phosphatase (Na+ K

+

ATPase) activity, serum marker enzymes, serum

bilirubin, glycogen and TBARS against APAP

(200mg/kg, p.o.) induced damage in Albino rats

(either sex) liver was studied to know possible

mechanism of hepatoprotection. The extract

prevented the toxic effects of APAP on the serum

parameters and stimulated hepatic regeneration

through an improved synthesis of protein or

accelerated detoxification and excretion18

.

The effect of various flavonoids (quercetin-3-

methyl-ether, quercetin-3, 7-dimethyl-ether and

kaempferol-3, 7-dimethyl-ether) isolated from leaves

of Cistus laurifolius Linn. (Cistaceae) were assessed

on lipid peroxidation, cellular GSH, serum AST and

ALT enzyme levels in APAP (800mg/kg, p.o.)

induced liver damage in male Swiss Albino mice. At

dose level (114mg/kg, p.o.) quercetin-3, 7-dimethyl-

ether showed potent antioxidative and

hepatoprotective activity19

.

Aqueous extract (200mg/kg, p.o.) of Cleome

viscosa Linn. (Capparaceae) seeds showed protective

effect against hepatotoxicity induced by CCl4

(0.5ml/kg, i.p.) in male Wistar Albino rats. The

extract protected the rats from hepatotoxicity

evidenced by significant reduction in serum enzymes

AST, ALT, ALP, Y-glutamyl transpeptidase and lipid

peroxidase and elevation in GSH20

.

Ethanol extract (200mg/kg, p.o.) of Clerodendrum

inerme Linn. (Verbenaceae) leaves when screened for its hepatoprotective activity in CCl4 (0.5ml/kg, i.p.) induced liver damage in either sex of Swiss Albino mice and Wistar Albino rats, significantly decreased the serum enzyme (ALT, AST, and ALP), Triglycerides (TGL), Total Cholesterol (TC) and significantly increased the GSH level. Moreover, pre-treated with the extract prevented the effect of hepatotoxicity

21.

Cuscuta chinensis Lam. (Convolvulaceae) seeds

ethanol extract showed significant hepatoprotective

effect at dose levels, 125 and 250mg/kg, p.o. and

potentiate significant reduction in levels of GSH,

glutathione peroxidase (GPT) and ALP against APAP

(835mg/kg, i.p.) induced hepatotoxicity in male

Wistar Albino rats22

.

The effect of ethanol extract (100 and 250mg/kg,

p.o.) of whole plant of Eclipta alba Hassk.

(Asteraceae) when administered to APAP (500mg/kg,

p.o.) induced hepatic damaged Albino mice of either

sex protected hepatotoxic action as evidenced by

significant reduction in the elevated serum maker

enzymes levels and also showed 38% reduction in

serum ALT levels23

.

The combined hepatoprotective effect of bi-herbal ethanol extract was evaluated against CCl4 (2ml/kg, p.o.) induced hepatic damage in male Albino Wistar rats. The ethanol extract (50mg/kg, p.o.) in ratio of (1:1) of Elicpta alba Hassk. (Asteraceae) leaves and Piper longum Linn. (Piperaceae) seed restored the substantially elevated serum marker enzymes towards normal. In addition, bi-herbal extract significantly decreased the liver weight of intoxicated rats

24, 25.

Methanol extract (500mg/kg, p.o.) of Ficus carica Linn. (Moraceae) leaves exhibited a significant protective effect against liver damaged by CCl4 (1.5ml/kg, p.o., in olive oil) in male Wistar rats. Treatment with the extract significantly inhibited the elevation in serum AST, ALT levels and liver lipid peroxidation level

26.

The essential oil (0.4ml/kg, i.p.) extracted from

seeds of Foeniculum vulgare Mill. (Apiaceae)

inhibited the hepatotoxicity induced by CCl4

(0.8ml/kg i.p.) in male Sprague-Dawley rats with

evidence of decreased levels of serum AST, ALT,

ALP and TB27

.

The glycyrrhizin isolate from liquorice

(Glycyrrhiza glabra Linn.-Fabaceae) roots was

investigated on acute hepatitis induced by

lipopolysaccharide (LPS) and D (+) galactosamine

(D(+)GalN) (mix 25ng LPS/20mg D(+)GalN, i.v.) in

male BALB/c mice. Glycyrrhizin (50mg/kg, i.p.)

inhibited the increased serum ALT levels. Moreover,

glycyrrhizin also reduced the responsiveness of cells to

IL-18 (a potent inflammatory cytokine that regulates

autoimmune and inflammatory diseases produced by

Kupffer cells, β-cells and dendritic cells) in the liver

injury. Results suggested that glycyrrhizin inhibits the

LPS/ D (+)GalN induced liver injury by preventing

inflammatory responses and IL-18 production28

.

The juice of the leaves (200mg/kg, p.o.) and

ethanol extract (200mg/kg, p.o.) of Kalanchoe

pinnata Lam. (Crassulaceae) were investigated

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INDIAN J NAT PROD RESOUR, DECEMBER 2010

400

against CCl4 (2ml/kg, i.p., in liquid paraffin) induced

hepatotoxicity in Wistar Albino rats of either sex. The

study confirmed that juice is more effective

hepatoprotective as compared to ethanol extract29

.

Ethanol extract of the bark of Lawsonia alba Linn.

(Lythraceae) showed a significant hepatoprotective

effect against CCl4 (1 ml/kg, p.o.) induced oxidative

stress in male Albino Wistar rats. Pre-treatment with

extract at dose levels of 250 and 500 mg/kg, p.o.

significantly lowered the serum transaminase GSH,

GPT, lactate dehydrogenase (LDH) levels. In

addition, extract inhibited the peroxidation of

microsomal lipids in dose dependent manner30

.

Chloroform extract (200 and 400 mg/kg, p.o.) of

aerial parts of Leucas lavandulaefolia Rees (Lamiaceae)

exhibited a significant protection in D(+)GalN (400

mg/kg, i.p.) induced liver damaged in male Wistar rats.

Treatment with extract showed significant decrease in

serum AST, ALT, ALP, TB, LDH, TC levels when

compared with intoxicated group31

.

The different extracts, petroleum ether, acetone and

methanol (250 mg/kg, p.o.) of Luffa echinata Roxb.

(Cucurbitaceae) fruit showed a significant

hepatoprotective activity comparable to standard drug

silymarin against CCl4 (1 ml/kg, s.c.) induced

hepatotoxicity in Wistar Albino rats32

.

Pretreatment with aqueous extract (100mg/kg, p.o)

of fruits of Lycium chinense Mill. (Solanaceae)

showed a significant protective effect by lowering the

serum AST, ALT and ALP. In addition, pre-treatment

with extract prevented the elevation of hepatic

malondialdehyde (MDA) formation, the depletion of

GSH content and catalase activity in the liver of CCl4

(0.5 ml/kg, s.c.) intoxicated male Sprague-Dawley

rats. The extract also displayed hydroxide radical

scavenging activity in a dose dependent manner33

.

The n-hexane extracts (100 and 200 mg/kg, p.o.) of

Lygodium flexuosum Swartz. (Lygodiaceae) whole plant

showed complete protection in D(+)GalN (800 mg/kg,

i.p.) induced liver injury in Wistar rats of either sex as

evident by normal serum AST, ALT and LDH levels,

hepatic GSH and MDA levels and also by normal

histological index of liver in extract treated rats34

.

The hepatoprotective activity of aqueous extracts

of leaves (500 mg/kg, fresh wt., 50mg/kg, dry wt.,

p.o.) of Momordica subangulata Blume

(Cucurbitaceae) and whole plant suspension (500

mg/kg, p.o.) of Naragamia alata W& A (Meliaceae)

were studied in APAP overdose (2 g/kg, p.o., in 40%

w/v aqueous sucrose solution) induced liver damage

in Wistar Albino rats. The extracts showed significant

protective effects35

.

Combination of 70% ethanol extracts of the roots of

Paeonia lactiflora Pall. (Paeoniaceae) and Astragalus

membranaceus Bunge (Fabaceae) demonstrated more

significant hepatoprotective activity than the herbs

when used individually in liver fibrosis induced in

male Sprague-Dawley rats with CCl4 (1 ml/kg, s.c.).

Moreover, administration of the combined extracts (40,

80 and 160 mg/kg, i.g.) significantly decreased the

elevation of serum transaminase activities, hyaluronic

acid, laminin and procollagen type III levels and

contents of hydroxyproline in liver tissue by

approximately 30-60%36

.

The n-hexane extract (200 mg/kg, p.o., in 5%

Tween-80) of whole plant of Phyllanthus

maderaspatensis Linn. (Euphorbiaceae) showed a

remarkable and better hepatoprotective activity than

standard drug silymarin against APAP (2 g/kg, p.o., in

40%w/v aqueous sucrose solution) induced

hepatotoxicity in Charles Wistar rats as justified from

the serum marker enzymes. Whereas, the aqueous and

ethanol extracts showed moderate activity as

compared to the n-hexane extract 37

.

Alcohol extract (50%) in 100 mg/kg, p.o. dose and

mixture of lignans, isolated from leaves of

Phyllanthus niruri Linn. (Euphorbiaceae) showed

significant hepatoprotective activity against APAP

(500 mg/kg, p.o., in 0.9% saline) induced liver cell

damage in Albino mice. The extract and lignans

mixture completely prevented the toxic effects of

APAP on the serum parameters by the stimulation of

hepatic regeneration through an improved synthesis of

protein or accelerated detoxification and excretion38

.

Ethanol extract (200 mg/kg, p.o., in Tween-80) of

whole plant of Phyllanthus rheedii Wight

(Euphorbiaceae) was pharmacologically analysed for

its preventive effect in D(+)GalN (800 mg/kg, i.p., in

normal saline) induced liver damage in Wistar rats of

either sex. The levels of serum parameters (ALT,

AST, ALP and TB) and tissue parameters (LDH and

TBARS) were decreased significantly in extract

treated group when compared to intoxicated group39

.

Aqueous extract of roots of Platycodon

grandiflorum (Jacq.) A. DC. (Campanulaceae)

showed a protective effect against APAP (400 mg/kg,

i.p., in saline) induced hepatotoxicity in male ICR

mice. Hepatic GSH and glutathione-S-transferase

(GST) activities were not affected by treatment with

the extract alone. However, pre-treatment with the

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CHAUDHARY et al: HERBS AS LIVER SAVERS– A REVIEW

401

extract protected the APAP induced depletion of

hepatic GSH levels. This effect of the extract on

cytochrome P450, 1A2 and 2 E1 (major isoenzymes

involve in APAP bioactivation) were investigated.

The protective effect was due to extract ability to

block P450 mediated APAP bioactivation40

.

The ethanol extract (200 mg/kg, i.p.) of the oyster

mushroom Pleurotus ostreatus (Jacq.) Quelet

(Pleurotaceae) on CCl4 (2 ml/kg, i.p., in olive oil)

induced liver damage in male Albino Wistar rats

showed a significant hepatoprotective activity.

Significant elevated levels of MDA and lowered levels

of GSH were observed in toxicated liver. In addition,

extract treated group serum AST, ALT and ALP levels

reverted towards normal, while the hepatic

concentration of GSH, CAT, SOD and Gpx were

significantly increased and MDA significantly lowered

when compared to intoxicated untreated group41

.

Chloroform extract (200 and 400 mg/kg, p.o.) of

leaves of Polygala arvensis Willd. (Polygalaceae)

exhibited a significant protective effect when compared

to standard drug silymarin (P<0.001) by normalizing

the levels of serum AST, ALT, ALP, TB, LDH, TC,

TGL, albumin and total proteins (TP) which were

significantly (P<0.001) increased in male Wistar rats

intoxicated with D(+)GalN (400 mg/kg, i.p)42

.

Aqueous extract (5ml/kg, i.p.) of leaves of Rhodococcum vitis idaea (Linn.) Avrorin (Ericaceae) significantly inhibited the hepatotoxicity and oxidative stress induced by D(+)GalN (700 mg/kg, s.c.) evident by an increase in serum alanine aminotransferase and GSH activities and lipid peroxidation in liver of male Wistar rats. The extract showed a potent antioxidant and protective property

43.

The different extracts ethanol, ethyl acetate and n-butanol (400 mg/kg, p.o.) of aerial parts of Schouwia

thebica Webb. (Brassicaceae) showed significant hepatoprotective activity. These extracts significantly reduced the increased levels of serum ALT, AST, glucose, TGL and TC in CCl4 (2.5 ml/kg, p.o., in corn oil) intoxicated male Sprague-Dawley rats. The activity was related to the presence of flavonoids in the extracts

44.

Treatment with the ethanol extracts (25 mg/kg, i.p.) of seeds of Silybum marianum Linn. (Asteraceae) and Cichorium intybus Linn. (Asteraceae) reduced the levels of enzymes activity (serum AST, ALT and ALP) and the level of TB in thioacetamide (50 mg/kg, i.p.) intoxicated Wistar male rats. Values of sodium, potassium and liver weight showed no significant difference. The protective effects of these extracts

were due to the presence of flavonoids and their antioxidant potential

45.

The protective effects of chloroform extract (100

mg/kg, p.o.) Terminalia catappa Linn. (Combretaceae)

leaves on CCl4 (10ml/kg, i.p., in olive oil) induced liver

damage in male ICR mice was studied. Serum AST

and ALT activities increased remarkably (2.0-fold and

5.7-fold, respectively) after the CCl4 injection. In

addition, the liver lipid peroxidation level in

intoxicated group showed 2.8-fold increase of that in

the normal group. However, treatment with various

concentrations of the extract (20, 50 and 100 mg/kg)

blocked the above changes significantly in a dose

dependent manner and the elevations in serum AST

and ALT activities and liver lipid peroxidation level

were inhibited almost completely46

.

The protective effect of ethyl acetate extract (25

mg/kg, i.p.) of aerial parts of Teucrium polium Linn.

(Lamiaceae) showed potential anti-lipidperoxidative

and antioxidant activities in female Albino Wistar rats

with CCl4 (3 ml/kg, i.p.) induced hepatotoxicity. The

elevated levels of blood marker enzymes (GPx and

SOD) and biochemical parameters (GSH and

TBARS), returned towards normal in groups treated

with silymarin (25 mg/kg, i.p.) and ethyl acetate extract

which clearly manifest their anti-hepatotoxic effect47

.

Ethanol extract (100 and 200 mg/kg, p.o., in 50%

w/v aq. sucrose solution) of leaves of Trianthema

portulacastrum Linn. (Aizoaceae) showed a

significant dose dependent protective effect against

APAP (3 g/kg, p.o., 1 h after ethanol extract

administration) and thioacetamide (100 mg/kg, s.c.,

2% w/v solution in distilled water) induced

hepatotoxicity in Wistar Albino rats of either sex. The

degree of protection was measured using biochemical

parameters like serum AST, ALT, ALP, TB and TP.

The extract completely prevented the toxic effects of

APAP and thioacetamide by stimulating the hepatic

regeneration through an improved synthesis of protein

or accelerated detoxification48

.

Ethanol extract (300 mg/kg, p.o.) of Tridax

procumbens Linn. (Asteraceae) aerial parts was

investigated against D(+)GalN/LPS (300 mg/kg, i.p.)

induced hepatic damage in male Wistar Albino rats by

a significant increase in the activities of serum marker

enzymes (AST, ALT, ALP, LDH and gamma

glutamyl transferase), TB and lipids levels both in

serum and liver. Pretreatment of extract afforded a

significant protection against liver injury by

maintaining these levels to nearly normal49

.

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Alcohol (200 and 500mg/kg, p.o., in Tween-80)

and aqueous (125 and 300mg/kg, p.o., in Tween-80)

extracts of leaves of Tylophora indica (Burm.f.)

Merrill, (Asclepiadaceae) showed protective effects

on ethanol (3.76g/kg, p.o.) induced hepatotoxicity in

male Wistar Albino rats. Pretreatment of extracts

significantly prevented the physical (increased liver

weight and volume), biochemical (increase in serum

ALT, AST, ALP, TB, TC, TGL and albumin),

histological (damage to hepatocytes) and functional

(thiopentane induced sleeping time) changes in

animals50

.

Some more medicinal plants (Plate 1) which are proved as hepatoprotective are described in Table 1. Most commonly used plants Adhatoda vasica Nees., Aloe barbadensis Mill., Andrographis paniculata Nees, Azadirachta indica A. Juss., Eclipta alba Hassak., Lawsonia alba Lam., Picrorhiza kurroa Royle ex Benth., Silybum marianum Linn. (are scientifically validated in experimental animal models and used by topmost companies as ingredients of herbal formulations for liver disorders for example., Amazon liver support, Bhumyamlaki, G-LIV-DS

Syrup, Hepta-B, Hepato-guard, Livotone, Liv up, Livpar, Liv-52, Milk Thistle complex, Stimuliv, Tefroli, V- gel and Yakrit Plihantak Churna.

The present review is an attempt to systematically

summarize the current scientific evidence regarding

the medicinally valuable plants, herbal drugs and their

constituents, especially in-regards to their presumed

beneficial effect to protect liver and delineates the

issues that need to be addressed to incorporate herbal

medicine into the arsenal of therapies in the treatment

of liver diseases. Plant drugs (combinations or

individual drug) for liver diseases must possess

sufficient efficacy to cure severe liver diseases caused

by toxic chemicals, viruses (Hepatitis B, Hepatitis

C, etc.) and excess alcohol intake51

.

Conclusion In spite of tremendous strides in modern medicine,

there is hardly any drug that stimulates liver

functions, protect liver from damage or help

regenerating hepatic cells. However, a number of

drugs are employed in traditional system of medicine

for liver affections and show promising

Plate 1: Some hepatoprotective plants

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Table 1―Some more plants proved to be hepatoprotective against various hepatotoxins

Plant Parts used Extract Dose Toxicant/s

Acalypha racemosa Wall. (Euphorbiaceae)52 Leaves Methanol extract 60 and 120mg/kg, p.o. CCl4 (1.5ml/kg, i.p.)

Actinidia deliciosa Chev. (Actinidiaceae)53 Roots Ethanol extract 60 and 120mg/kg, p.o. CCl4 (2ml/kg, s.c.)

Aegle marmelos Corr. (Rutaceae)54 Leaves Ethanol extract 1g/kg, p.o. EtOH (30%) (1ml/kg,

p.o.)

Annona squamosa Linn . (Annonaceae)55 Leaves Ethanol extract

Aqueous extract

350mg/kg, p.o.

300mg/kg, p.o.

INZ (100mg/kg, i.p.)

RFN (100mg/kg, i.p.)

Aspalathus linearis (Brum.f) Dahlg

(Theaceae)56

Leaves Aqueous extract 5ml/kg, p.o. CCl4 (1ml/kg, i.p.)

Bauhinia variegate L. (Fabaceae)57 Stem bark Ethanol extract 100 and 200mg/kg, p.o. CCl4 (1ml/kg, s.c.)

Berberis tinctoria Lesch. (Berberidaceae)58 Leaves Methanol extract 150 and 300mg/kg, p.o. APAP (750mg/kg, p.o.)

Boswellia serrata Roxb. (Burseraceae)59 Oleo gum

resin

n-Hexane extract 87.5 and 175mg/kg, p.o. CCl4 (0.5ml/kg, p.o.)

APAP (2g/kg, p.o.)

TAA (100mg/kg, s.c.)

Butea superba Roxb. (Fabaceae)60 Stem bark Ethanol extract 50 and 100mg/kg, p.o. CCl4 (0.1ml/kg, i.p.)

Cajanus indicus Linn. (Fabaceae)61 Leaves Protein fraction 2mg/kg, i.p. APAP (300mg/kg, p.o.)

Capparis spinosa Linn. (Capparidaceae)62 Roots Ethanol extract 100, 200 and 400mg/kg,

p.o.

CCl4 (0.2mg/kg, p.o.)

Cassia occidentalis Linn. (Fabaceae)63 Roots Aqueous extract 200mg/kg, p.o. CCl4 (2ml/kg, i.p.)

Careya arborea Roxb. (Myrtaceae)64 Stem bark Methanol extract 50, 100 and 200mg/kg, p.o. CCl4 (1ml/kg, i.p.)

Camellia sinensis Linn. (Theaceae)65 Leaves Aqueous extract 200mg/kg, p.o. and

1.5% of extract, p.o.

SO (100mg/kg, i.p.)

TXN (45mg/kg, i.p.)

Cichorium intybus Linn. (Asteraceae)66 Leaves Ethanol extract 50, 100 and 200mg/kg, i.p. CCl4 (3ml/kg, i.p.)

Commiphora opobalsamum Linn.

(Burseraceae)67

Aerial parts Ethanol extract 250 and 500mg/kg, p.o. CCl4 (0.25ml/kg, i.p.)

Croton zehntneri Pax et Hoff.

(Euphorbiaceae)68

Leaves Essential oil 30, 100 and 300mg/kg, p.o. APAP (500mg/kg, p.o.)

Curculigo orchioides Gaertn.

(Amaryllidaceae) 69

Rhizomes Methanol extract 70mg/kg, p.o. CCl4 (1ml/kg, s.c.)

Curcuma longa Linn. (Zingiberaceae)70 Rhizomes Ethanol extract 200 and 100mg/kg, p.o. INZ (50mg/kg, p.o.)

RFN (100mg/kg, p.o.)

PZA (300mg/kg, p.o.)

APAP (600mg/kg, p.o.)

Diospyros malabarica (Desr.) Kostel.

(Ebenaceae)71

Bark Methanol extract 200 and 300mg/kg, p.o. CCl4 (1ml/kg, i.p.)

Enicostemma axillare Lam. (Gentianaceae)72 Leaves Ethanol extract 0.66g/kg, p.o. and Roots CCl4 (0.7ml/kg, i.p.)

Epaltes divaricata Casso. (Asteraceae)73 Whole plant Aqueous extract 0.9g/kg, p.o. CCl4 (0.5ml/kg, i.p.)

Ervatamia coronaria Stapf. (Apocynaceae)74 Leaves Methanol extract 100 and 200mg/kg, p.o. CCl4 (1ml/kg, i.p.)

Euphorbia antiquorum Linn. (Euphorbiaceae)75 Aerial parts Aqueous extract 125 and 250mg/kg, p.o. CCl4 (1ml/kg, p.o.)

Ginkgo biloba Linn. (Ginkgoaceae) 76 Leaves Dry extract Ginkgolides (50mg/kg, i.p.) CCl4 (0.5ml/kg, i.p.)

Hygrophila spinosa T. Anders (Acanthaceae)63 Roots Aqueous extract 20mg/kg, p.o. CCl4 (2ml/kg, i.p.)

Ichnocarpus frutescens Linn. (Apocynaceae)77 Whole plant Chloroform extract

Methanol extract

250 and 500mg/kg, p.o. APAP (750mg/kg, p.o.)

Indigofera trita Linn. (Fabaceae)78 Whole plant Ethanol extract 200 and 400mg/kg, p.o. CCl4 (1ml/kg, i.p.)

Launaea pinnatifida Cass. (Asteraceae)79 Leaves and

roots

Ethanol extract 0.66g/kg, p.o. CCl4 (0.5ml/kg, i.p.)

Leucophyllum frutescens Berl.

(Scrophulariaceae)80

Aerial parts Methanol extract 100 and 200mg/kg, p.o. CCl4 (2ml/kg, p.o.)

Momordica dioica Roxb. (Cucurbitaceae)81 Roots Ethanol extract 200mg/kg, p.o. CCl4 (0.4ml/kg, i.p.)

Contd.

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hepatoprotective activity. Since the evidence supporting the use of botanicals to treat chronic liver diseases is insufficient and only few of them are well standardised and free of serious side effects. Particularly with regard to adequately powered randomised-controlled clinical trials with well-selected end points are needed to assess the role of herbal therapy for liver diseases.

Pharmacological validation of each

hepatoprotective plant should include efficacy

evaluation against liver diseases induced by various

agents, efficacy against viral hepatitis as well as liver

damage induced by hepatotoxic chemicals by

oxidative mechanisms or other mechanisms. Further,

the plant drugs have to be evaluated for their effects

on liver regeneration and bile secretion.

Table 1―Some more plants proved to be hepatoprotective against various hepatotoxins―Contd.

Plant Parts used Extract Dose Toxicant/s

Nelumbo nucifera Gaertn. (Nymphaeaceae)82 Flowers Ethanol extract 200 and 400mg/kg, p.o. CCl4 (1ml/kg, i.p.)

APAP (3g/kg, p.o.)

Nigella sativa Linn. (Ranunculaceae)83 Seeds Ethanol extract 800mg/kg, p.o. CCl4 (1.15ml/kg, s.c.)

Ocimum santum Linn. (Lamiaceae) 84 Leaves Ethanol extract 200mg/kg, p.o. INZ (27 mg/kg/day)

RFN (54 mg/kg/day)

PZA (135 mg/kg/day)

Parkinsonia aculeate Linn. (Fabaceae) 85 Leaves Ethanol extract 100, 200 and 300mg/kg,

p.o.

CCl4 (1ml/kg, i.p.)

Pergularia daemia Forsk (Asclepiadaceae) 86 Aerial parts Ethanol extract 50, 100 and 150mg/kg, p.o. CCl4 (1.25ml/kg, i.p.)

Phoenix dactylifera Linn. (Arecaceae)87 Pits and flesh Aqueous extract CCl4 (0.2ml/100g, i.p.)

Phyllanthus polyphyllus Willd.

(Euphorbiaceae)88

Leaves Methanol extract 200 and 300mg/kg, p.o. APAP (750mg/kg, p.o.)

Pterocarpus santalinus Linn. (Fabaceae)89 Stem bark Aqueous extract

Ethanol extract

Aqueous - 45mg/ml and

Alcohol - 30mg/ml, p.o.

CCl4 (0.1ml/kg, i.p.)

Punica granatum Linn. (Punicaceae)90 Peel Powdered drug 10% of Basal diet CCl4 (0.5ml/kg, i.p.)

Raphanus sativus Linn. (Brassicaceae)91 Seeds Aqueous and

Methanol extract

200 and 400mg/kg, p.o. CCl4 (0.2ml/kg, i.p.)

Rhododendron arboretum Sm. (Ericaceae)92 Leaves Ethanol extract 40, 60 and 100mg/kg, p.o. CCl4 (1ml/kg, s.c.)

Ricinus communis Linn. (Euphorbiaceae)93 Leaves n-Hexane –

Chloroform as

eluent

3-Bromo-6-(4-chlorophenyl)

-4-methylthio-2H-pyran-2-

one

(6mg/kg, p.o.)

CCl4 (0.7ml/kg, i.p.)

APAP (2mg/kg, p.o.)

TAA (400mg/kg, s.c.)

Rubia cordifolia Linn. (Rubiaceae)94 Roots Methanol extract 100mg/kg, i.p. TAA (100mg/kg, s.c.)

Sarcostemma brevistigma Wight

(Asclepiadaceae)95

Stem Ethyl acetate extract 650mg/kg, p.o. CCl4 (1.25ml/kg, p.o.)

Saponaria officinalis Linn. (Caryophyllaceae)90 Powdered drug 10% of Basal diet CCl4 (0.5ml/kg, i.p.)

Smilax chinensis Linn. (Liliaceae)96 Roots Ethyl acetate extract 100mg/kg, p.o. APAP (750mg/kg, p.o.)

Solanum trilobatum Linn. (Solanaceae)97 Whole plant Ethanol extract 250mg/kg, p.o. CCl4 (1ml/kg, i.p.)

Swertia longifolia Boiss (Gentianaceae)98 Aerial parts Ethanol extract 200mg/kg, p.o. APAP (600mg/kg, i.p.)

Syzygium aromaticum Linn. (Myrtaceae)99 Flower buds Ethanol extract 500mg/kg, p.o. APAP (600mg/kg, i.p.)

Terminalia belerica Roxb. (Combretaceae)100 Fruits Aqueous extract

Ethanol extract

200 and 400mg/kg, p.o. EtOH (30%) (3ml/kg,

p.o.)

Thespesia lampas Dalz. (Malvaceae)101 Roots Methanol extract 300mg/kg, p.o. CCl4 (3ml/kg, s.c.)

Tinospora cordifolia Willd.

(Menispermaceae) 102

Roots Ethanol extract 200mg/kg, p.o. INZ (50mg/kg, p.o.)

RFN (100mg/kg, p.o.)

PZA (300mg/kg, p.o.)

Trigonella foenum-graecum Linn.

(Fabaceae)103

Seeds Diethyl ether extract 0.5ml/kg, i.p. CCl4 (0.8ml/kg, i.p.)

Urtica parviflora Roxb. (Urticaceae)104 Leaves Ethanol extract 250, 500 and 700mg/kg, p.o. CCl4 (1ml/kg, s.c.)

Vetiveria zizanioides Linn. (Poaceae)105 Roots Methanol extract 300 and 500mg/kg, p.o. EtOH (20%) (3.76g/kg,

p.o.)

Vicia calcarata Desf. (Fabaceae)106 Aerial parts Ethanol extract Flavonoid- 2 25mg/kg, p.o CCl4 (100mg/kg, p.o.)

Xylopia phloiodora Mildbr. (Annonaceae)107 Stem bark

and leaves

Crude extract, Ether

extract and Essential

oil

50, 100 and 250mg/kg, p.o.

(Essential oil) 10% v/w

of 2.5kg Stem bark, p.o.

CCl4 (0.3ml/kg, i.p.)

APAP (500mg/kg, p.o.)

Zizyphus mauritiana Lamk. (Rhamnaceae)108 Seeds Ethanol extract 200mg/kg, p.o. INZ (50mg/kg, p.o.)

RFN (100mg/kg, p.o.)

PZA (300mg/kg, p.o.)

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CHAUDHARY et al: HERBS AS LIVER SAVERS– A REVIEW

405

Therefore, the most effective drug for each kind of

liver disease has to be selected by separate efficacy

evaluations. Pharmacovigilance of plant based drugs

be further improved and mechanisms of action must

be elucidated. There is still lot of work to be done in

order to achieve a reliable standardized products and

to link it to a specific biological activity and

therapeutic application.

Acknowledgement

The authors extend their sincere thanks to Shri

Parveen Garg (Chairman, I.S.F. College Of

Pharmacy, Moga) for his co-operation and for

providing the required institutional facilities.

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