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CARDIOPROTECTIVE ROLE OF TERMINALIA CATAPPA. Linn AND CISSAMPELOS PAREIRA. Linn ON DOXORUBICIN
INDUCED CARDIAC TOXOCTIY IN RATSTHESIS
Submitted toJawaharlal Nehru Technological University, Anantapur,
In the partial fulfillment of the requirements for
the award of the degree of
MASTER OF PHARMACY
IN
PHARMACOLOGY
By
Y.LALITHA
[Reg.No.10AF1SO108]
Under the guidance of
V. JAYA SANKAR REDDY M.Pharm, (Ph.D)
Department of Pharmacology
KRISHNATEJA PHARMACY COLLEGE, TIRUPATHI, CHITTOOR (Dt)
SEPTEMBER -2012
AIM AND OBJECTIVE OF THE STUDY
The Goal of the present study is to investigate
• Cardiac protective activity of Terminalia catappa.L and Cissampelos pareira.L
against doxorubicin induced cardiac toxicity in rats.
The following objectives were set to achieve the goal of the present study
• To perform the acute toxicity studies of ethanolic extracts of Terminalia
catappa.L and Cissampelos pareira.L on mice.
• To investigate the effect of various doses of Terminalia catappa.L and
Cissampelos pareira.L on serum biomarkers (CK, LDH, SGOT, SGPT) in
normal and cardio toxic rats.
• To investigate the effect of various doses of Terminalia catappa.L and
Cissampelos pareira.L on antioxidant enzymes (SOD and catalase) in normal
and cardio toxic rats.
PLAN OF WORK
Plant selection and acquisition
Botanical identification
Drying of plant materials
Extraction of plant materials
Phytochemical profiling
Acute toxicological studies
Screening of cardio protective activity
INTRODUCTION
• Cardiovascular diseases remain the principal cause of death in
both developed and the developing countries.
• Myocardial infarction is a prominent implication of the
cardiovascular disease. According to WHO 16.7 million
people die each year owing to heart attacks.
• Traditionally, Terminalia catappa.Linn and Cissampelos
pareira.Linn were used as cardio-tonics and
pharmacologically both shown significant antioxidant
property, hence these plants were chosen to evaluate the
Cardio protective Activity.
• Doxorubicin, a successful antitumor drug also known for its
cumulative and dose dependent cardio toxicity. Hence Dox
has been chosen for the study to induce cardio toxicity.
MYOCARDIAL INFARCTION
• Myocardial infarction is an ischemic necrosis of a portion of the
myocardium due to sudden occlusion of a branch of coronary artery.
CLASSIFICATION:
. ST elevation MI(STEMI)
. Non- ST elevation (non-STEMI)
EPIDEMOLOGY:
• MI is a common occurrence in young man(40-60yrs) and in
women (60-85yrs).
• World wide more than three million people were suffering
with STEMI and more than four million people were suffering
with Non-STEMI.
• Blacks and whites are equally affected.
• Mortality estimates due to CVD vary widely by state, ranging
from 10% in Meghalaya to 49% in Punjab.
AEITOLOGY:
• Hypercholesterolemia
• Diabetes mellitus
• Smoking
• Stress
• Obesity
• Insufficient exercise
• Hypertension
SYMPTOMS:
• Pain
• Difficulty in breathing
• Dizziness
• Nausea
• Shortness of breath
• Mimics like MI
Pathophysiology:
Role of plaque in MI
DIAGNOSIS OF MYOCARDIAL INFARCTION
• The diagnosis of myocardial infarction can be made after
assessing patient's complaints and physical status.
• ECG changes, Coronary angiogram and levels of cardiac
markers help to confirm the level of infarction.
MYOCARDIAL INFARCTION COMPLICATIONS
• Arrhythmias
• Heart failure
• Pericarditis
• Emboli
PLANT PROFILE
Terminalia catappa.L Cissampelos pareira.L
TAXONOMY:
Kingdom :Plantae
Division :Magnoliophyta
Class :Magnoliopsida
Order :Myrtales
Family :Combrataceae
Genus : Terminalia
Species :catappa
TAXONOMY:
Kingdom : Plantae
Division :
Magnoliophyta
Class : Magnoliopsida
Family :
Menispermaceae
Genus : Cissampelos
Species : Pareira
Uses
Terminlia catappa.Linn
It has been used for dysentry,
rheumatoid arthritis, cough,
asthma, leprosy, nausea, eye
problems, liver problems and
STD.
It is used as cardiotonic, diuretic,
antipyretic, aphrodisiac and
antimicrobial agent.
Cissampelos pareira. Linn
It has been used for heart
problems,asthma,inflammat
ion, malaria, STD, snake
bite and Kidney problems.
It has been used as diuretic,
antiseptic and anti periodic
property.
REVIEW OF LITERATURETerminlia catappa. l
S.NO Authors & year Activity done1 B.V.Jawal et al.,(2012) Antioxidant potential
2 Abulmanzur et al.,(2011) Antimicrobial activity
3 A. Aimola et al., (2011) Erythropoiesis
4 Azrul et al.,(2011) Anthelmintic potential
5 Paul chidokachikezie (2011) Antipolymerization
6 Saheb L and SS Wadje.,(2011) Fungicide activity
7 Saroja M et al.,(2011) Antioxidant activity of phenolic fraction
8 H.V Annegowda et al.,(2010) Analgesic and antioxidant properties
9 Jing gao et al.,(2010)Kinoshita S et al.,(2007)
Hepatoprotective activity
10 Minakshi G Joshi et al., (2008) Antibiotic
11 Ahmed SA et al.,(2006) Antidiabetic activity
12 Fan YM et al., (2004) Phytochemical and anti-inflammatory activity
Cissampelos pareira.L
S.NO Authors & year Activity done1 Singh BK et al., (2012) Cardiac protective activity
2 Mahendra sigh Yadv etal.,(2011)
Hepatoprotective activity
3 PadminiShukla et al., (2011) In-vitro anthelmintic activity
4 Pramodine d et al., (2011) Memory enhancing activity
5 Surendran S et al., (2011) Hepatoprotective activity
6 Gupat M et al.,(2010) Antipyretic activity
7 Bafna A, Mishra S.,(2009) Immunomodulatory activity
8 Amresh G et al., (2008) Toxicological screening
9 Amresh G et al., (2007) Antinociceptive and antiarthritic
10 G. Amresh et al., (2011) Gastroprotective
11 AmreshG,Reddy GD et al., (2007)
Antioxidant activity
• MATERIALS:
Animals: Wistar rats(150-200gms)
Swiss albino mice(20-30gms)
S.NO Chemical Manufacture
1 Doxorubicin Celon
2 Normal saline Claris life sciences Ltd
3 CK-MB kit span diagnostics Ltd
4 SGOT kits span diagnostics Ltd
5 SGPT kits span diagnostics Ltd
6 Formalin Sd-fine chem. Limited
7 Potassium dihydrogen phosphate Merk specialities
8 Ethanol Changshuyangyuan chemicals
9 Disodium hydrogen phosphate Fisher scientific
• METHODS
Identification and authentification of plants
Collection of plant materials
preparation of plant materials for the extraction
Extraction procedure
Preliminary phytochemical studies
ACUTE TOXICITY STUDIES
The procedure was followed by using OECD 423 (Acute Toxic
Class Method).
The starting dose level of Terminalia catappa.L and
Cissampelospareira.L was 2000 and 5000mg/kg body weight p.o.
Dose was administered to overnight fasted mice`s. Food was
withheld for and further 3-4 hours after administration.
The body weight of the mice`s before and after administration were
noted.
the changes in the body weight were not so prominent.
The onset and signs of toxicity was also not observed. No mortality
was observed.
PHARMACOLOGICALSCREENING
GROUPING:
• Group I : Control (Normal control)
• Group II : Positive control(doxorubicin(15 mg/kg B.W, through I.P))
• Group III: Test I (Plant Extract-250mg/kg B.W of EETC+DOX)
• Group IV : Test II (Plant Extract-500mg/kg B.W of EETC+DOX)
• Group V : Test III(plant extract-250mg/kg B.W of EECP+DOX)
• Group VI : Test IV (Plant extract-500mg/kg BW of EECP+DOX)
• Group VII: Test V(DOX+Plant Extract-250mg/kg B.W of
EETC)
• Group VIII: Test VI(DOX+Plant Extract-500mg/kg B.W of
EETC)
• Group IX: Test VII(DOX+ Plant extract-250mg/kg B.W of
EECP)
• Group X: Test VIII(DOX+ Plant extract-500mg/kg B.W of
EECP)
• Rats were divided into ten groups each group contain six animals.
• Group I serves as normal which receives normal saline(5ml/kg
B.W) for 30 days and Group II serves as positive control which
receives doxorubicin 7.5mg/kg B.W in two equal injections at
27thand 29th day(15mg/kg B.W; I.P route)and normal
saline(1ml/kg B.W).
• Group III, Group IV, Group V and Group VI serves as test
which receives plant extracts of Terminalia catappa.L and
Cissampelos pareira.L at dose of 250 and 500 mg/kg B.W,
through oral route throughout the study period and also receives
doxorubicin (15 mg /kg B.W) at 27thand 29thday.
• Group VII, Group VIII, Group IX and Group X also serves as test
and receives doxorubicin(15 mg/kg B.W) first and then receives test
extracts at an dose of 250 and 500mg/kg B.W, through oral route
throughout the study period.
• After the study period animals were sacrificed by collecting blood
through cardiac puncture and collected blood was centrifuged and
serum was collected and biochemical analysis were performed for
serum levels CK-MB, LDH, SGOT, SGPT, SOD and Catalase.
• The hearts were isolated and placed in 10% formalin and
histopathological studies were performed.
RESULTS Phytochemical analysis:
+VE: Presence of compound
-VE : Absence of compound
S.NO COMPOUNDS
ETHANOLIC EXTRACT OF
TERMINALIA CATAPPA
ETAHANOLIC EXTRACT OF
CISSEMPELOS PAREIRA
1 Carbohydrates + +
2 Fixed oils + +
3 Alkaloids + +
4 Glycosides + +
5 Steroids + +
6 Flavonoids + +
7 Tannins + +
8 Phenolic compounds + +
9 Amino acids - -
10 Saponins + +
Acute toxicological study:
• From acute toxicity studies their was no mortality at a dose
of 5000mg/kg B.W.
Pharmacological screening: Effect of ethanolic extracts of Terminalia catappa. L and
Cissampelos pareira. L on serum biomarkers in normal and doxorubic in exposed rats
S.NO Groups CK-MB LDH SGOT SGPT
1 Group I 126.20±2.584 116.79±2.412 68.6±4.188 46.213±0.7026
2 Group II 246.52±6.609 234.76±4.889 161.98±0.7525 92.82±1.898
3 Group III 181.00±2.369*** 143.22±4.770*** 140.23±1.074*** 81.35±0.7794***
4 Group IV 152.80±7.061* 136.65±3.484*** 116.68±1.145*** 68.68±0.8520***
5 Group V 171.49±2.513*** 137.22±4.019*** 130.80+4.414*** 73.67±1.433***
6 Group VI 156.10±2.768** 120.49±5.220*** 87.53±6.7332*** 57.23±0.9472***
7 Group VII 223.28±8.677*** 198.25±3.146*** 178.51±2.785** 78.32±0.8053***
8 Group VIII 192.84±5.893*** 178.52±2.276*** 146.14±1.837* 69.21±1.686***
9 Group IX 178.12±3.503*** 147.22±2.742*** 126.61±4.753*** 68.88±1.879***
10 Group X 149.70±2.876* 133.86±2.883*** 88.248±3.664*** 51.84±1.501***
Effect of ethanolic extracts of EETC and EECP on antioxidant levels in doxorubicin treated rats hearts
All values were expressed as mean+ SEM; n= 6 observation, values were significant when compared with
positive control, * P<0.05,** P<0.01,*** P<0.001(one way ANOVA followed by Turkey`s test)
S.NO GROUPS SOD CATALASE
1 Group I 7.1±0.03890 11.24±0.1472
2 Group II 3.747±0.2449 5.07±0.1451
3 Group III 5.168±0.08392*** 7.75±0.2808***
4 Group IV 5.597±0.2800*** 9.12±0.1183***
5 Group V 4.980±0.2493** 8.30±0.2516***
6 Group VI 6.112±0.1657*** 10.250±0.07638***
7 Group VII 4.942±0.1241** 6.74±0.1700***
8 Group VIII 4.92±0.2554** 7.64±0.1148***
9 Group IX 4.97±0.1179** 8.54±0.2683***
10 Group X 5.900±0.3246*** 10.81±0.2629***
Effect of Terminalia catappa.L and Cissampelos pareira.L on serum CK, LDH, SGOT & SGPT levels in doxorubicin induced cardiac toxic rat
Histopathlogical studies
CONCLUSION
• The present study suggest that the Terminalia catappa.L and
Cissampelos pareira.L could be used as an antioxidant during or
after doxorubicin therapy plants shows a greater protective effect in
preventive as compared with curative model in rats.
• Further studies should be required for the detection, isolation and
structural elucidation of the chemical constituents and further
investigation should be required to find exact mechanism of action
for cardioprotective activity of Terminalia catappa.L and
Cissampelos pareira.L plants.
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