RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
KARNATAKA, BANGALORE.
M. PHARM SYNOPSIS
YEAR OF ADMISSION-MAY 2009
TITLE OF THE SYNOPSIS
“AN INVESTIGATION OF CARDIOPROTECTIVE ACTIVITY OF
CEDRUS DEODARA ROXB HEARTWOOD EXTRACT ON
ISOPROTERENOL INDUCED MYOCARDIAL INFARCTION IN RATS”
By
Mr. NIRANJAN KUMAR B. M
M.PHARM, PART-I
DEPARTMENT OF PHARMACOLOGY
UNDER THE GUIDANCE OF
Mr. SYED MANSOOR AHAMED, M.Pharm.,(Ph.D)
ASSISTANT PROFESSOR
DEPARTMENT OF PHARMACOLOGY
INSTITUTION
SREE SIDDAGANGA COLLEGE OF PHARMACY
B.H.ROAD, TUMKUR-572 102
KARNATAKA.
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
BANGALORE, KARNATAKA
ANNEXURE-II
PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION
1.0 / NAME OF THECANDIDATE AND ADDRESS / Mr. Niranjan Kumar B. MSreeSiddaganga College of Pharmacy
B.H.Road, Tumkur. 572 102
Karnataka.
2.0 /
NAME OF THE INSTITUTION / Sree Siddaganga College of Pharmacy
B.H.Road, Tumkur. 572 102
Karnataka.
3.0 / COURSE OF STUDY AND SUBJECT / M.Pharm (Pharmacology)
4.0 / DATE OF ADMISSION TO COURSE /
May-2009
5.0 / TITLE OF THE TOPIC:
“AN INVESTIGATION OF CARDIOPROTECTIVE ACTIVITY OF
CEDRUS DEODARA ROXB HEARTWOOD EXTRACT ON ISOPROTERENOL INDUCED MYOCARDIAL INFARCTION IN RATS”
6.0
7.0
8.0 / BRIEF RESUME FOR INTENDED WORK
6.1. NEED FOR STUDY:
Cardiovascular diseases are the major causes of disability and premature deaths in both developed and developing countries accounting for roughly 20% of all world wide deaths due to myocardial infarction1. According to World Health Organisation (WHO), it will be a major cause of death in the world by year 20202. Currently available management of cardiovascular disorders like arrhythmia, hypertensions, angina pectoris, congestive heart failure, myocardial infarction are problematic. In addition, conventional drugs used are sometimes inadequate and may lead to serious adverse effects. Streptokinase itself causes hypersensitivity reaction, hypotension, arrhythmia; Abciximab causes haemorrhage, arrhythmia; Diphyridamole causes risk of stroke in transient ischemia attacks3. It is therefore imperative to search alternative drugs for treatment of cardiovascular disorders to replace the currently available drugs with known efficacies and safety.
A number of medicinal plants have been evaluated for cardiovascular disorders in India and various parts of the world using cardiotoxic models. Isoproterenol (ISO) induced myocardial necrosis is a well known standard model to study the beneficial effect of many drugs on cardiac dysfunction. It is a β-adrenergic blocker agonist found to cause severe stress in the myocardium resulting in infarction like necrosis of heart muscles due to generation of high cytotoxic free radicals through auto oxidation of catechol amines and has been implicated as a causative factor2, 4.
The heartwood of Cedrus deodara Roxb. (Family: Pinacea) is used in ayurvedic medical practices for rheumatoid arthritis, inflammation, diabetes, renal and vascular calculi. It has also been used as digestive, carminative, cardio tonic and blood purifier5. The plant has been reported to possess mast cell stabilizing & lipoxygenase inhibitory activity6, spasmolytic7, antioxidant8, anti-inflammatory, analgesic, membrane stabilizing activity9 and immunomodulatory activity10. Recently it has been reported for anxiolytic and anticonvulsant activity11. However there is lack of information regarding the effect of Cedrus deodara Roxb on the cardiac changes associated with isoproterenol induced myocardial infarction. Hence we thought it will be worthwhile to screen the cardioprotective effect of Cedrus deodara Roxb on isoproterenol induced myocardial infarction.
6.2. REVIEW OF LITERATURE:
Cedrus deodara Roxb is well known as deodar (Family:Pinaceae). It is grown as an ornamental tree, and is a large evergreen tree found throughout the western himalayas, in an elevated range of 1050-3600 metres above sea level. The tree reaches up to a height of 60-85 metres with an almost rough, black, furrowed bark with spreading branches. The shoots are dimorphic, while the leaves are needle like, triquetrous, sharp and pointed; male cones are solitary, cylindric at the end of branchlets, female cones are solitary at the end of branchlets, composed of imbricating thin woody placental scales; seeds are pale brown in color with wings longer than the seeds. The heartwood of deodar is light yellow brown, turning brown on exposure to light5.
BOTANICAL CLASSIFICATION12:
Kingdom : Plantae
Division : Pinophyta
Class : Pinopsida
Order : Pinales
Family : Pinaceae
Genus : Cedrus
Species : deodara
Biological name : Cedrus deodara Roxb
Synonyms : English: Deodar cedar, Himalayan cedar or Deodar
Hindi: Deodar; Sanskrit: Devadaru; Kannada: Devadaru
Telugu: Devadaru; Tamil: Tevataram.
Chemical constituents are himachalol, allohimachalol, himadrol, dihydromyricetin, cedrinosid, phenolic sesquiterpene, oleo-resines, matairesional, cedeodarin, taxifolin, alkaloids, dibezylbutyrolactollignan, 5, 7-dihydroxyflavanonol, cedrin and minerals like calcium and phosphorus13.
In literature, it was found that different parts of this plant were useful in treating various diseases such as, the leaves of the plant in treatment of inflammations and tubercular glands; the heartwood is bitter and acrid and is used as a digestive and also as an anthelmintic, galacto-purifier, diuretic. It is also useful for rheumatoid arthritis,
renal and vesicle calculi and leucoderma. The oil is an antiseptic and is useful in treatment of leprosy, syphilis, wounds and ulcers5.
6.3. REPORTED ACTIVITES:
Mast cell stabilizing & lipoxygenase inhibitory activity6, spasmolytic activity7, antioxidant8, anti-inflammatory, analgesic, membrane stabilizing activity9, immune-
modulatory activity10, anxiolytic & anticonvulsant activity11.
6.4. OBJECTIVES OF PRESENT STUDY
The present work deals with the evaluation of cardioprotective activity of heartwood extract of Cedrus deodara Roxb with the following specific objectives.
1. Collection and Authentication of plant.
2. Preparation of ethanolic extract from heartwood of Cedrus deodara Roxb using
Soxhlet’s extractor.
3. To investigate the cardioprotective activity of the heartwood extract of Cedrus
Deodara Roxb on isoproterenol induced myocardial infarction in rats by measuring
the following parameters:-
I. Serum biomarkers
a) Alanine AminoTransferase (ALT).
b) Aspertate AminoTransferase (AST).
c) Lactate dehyrogenase (LDH).
d) Creatinine phosphokinase(CPK).
e) Serum Uric acid.
f) Albumin concentration.
II. Electro Cardio Graphic Changes. (Bio-pack)
III. Histopathological changes.
IV. Tissue antioxidant level.
A) Non-enzymatic antioxidant C) Enzymatic antioxidants
a) Glutathione. a) Catalase.
b) Total thiol. b) Superoxide dismutase.
.
B) Lipid peroxidation (Lpx)
MATERIALS AND METHODS
7.1. SOURCE OF DATA: (including sampling procedure, if any):
The sources of data will be from the laboratory experiments, which involves extraction from heartwood of Cedrus deodara Roxb and their pharmacological activities on experimental animals, such as adult male wistar rats.
EXPERIMENTAL ANIMALS:
Male wistar rats weighing 150-200 grams will be used .The animals will be maintained under controlled conditions of temperature (23 ± 2oC), humidity (50 ±5%) and 12 hours light and dark cycles. The animals are randomized into experimental and control groups and housed in sanitized polypropylene cages containing sterile paddy husk as bedding. They will also have free access to food and water.
7.2. ACUTE TOXICITY STUDIES:
The guidelines described by OECD will be adapted for the determination of LD50 on adult female wistar rats, as the female rats are more sensitive to toxins compared to male rats. 1/10th of LD50 dose will be taken for further studies.
7.3 EXPERIMENTAL DESIGN:
ISOPROTERENOL INDUCED MYOCARDIAL INFARCTION:
The male wistar rats will be and divided into 6 groups each group containing 6 rats and treatment would be as follows:-
GROUP / TREATMENT
I / Normal + Vehicle.
II / Normal + Cedrus deodara Roxb extract 2nddose.
III / Isoproterenol (200 mg/kg).
IV / Isoproterenol (200 mg/kg) + Cedrus deodara Roxb extract1stdose.
V / Isoproterenol (200 mg/kg) + Cedrus deodara Roxb extract2nd dose.
VI / Isoproterenol (200 mg/kg) + Vitamin-C.
Groups II, IV and V were pretreated with Cedrus deodara Roxb extract and group VI with Vit-C as standard for 28 days. After the pre treatment stage, isoproterenol
(200 mg/kg)2 will be subcutaneously injected to rats at an interval of 24 hours for
2 days to induce myocardial infarction. After 48 hours, the rats will be anaesthetized
and the electrocardiograph is recorded. Later the animal is subjected to decapition blood sample and heart specimen is collected, levels of biomarker and histological observations of the heart tissues and serum will be performed, as mentioned in the above objectives of study.
7.4. DOES THE STUDY REQUIRE ANY INVESTIGATION OR INTERVENTIONS TO BE CONDUCTED ON PATIENTS OR OTHER HUMANS / ANIMALS? IF SO PLEASE DESCRIBED BRIEFLY.
Yes, the above study requires investigation to be done on the male wistar rats for the
determination of cardioprotective activity.
7.5. HAS ANIMAL ETHICAL COMMITTEE CLEARANCE BEEN OBTAINED FROM YOUR INSTITUTION IN CASE?
The study has been referred to the ethical committee of the institution and clearance has been obtained (Approval No.79/2009-10, Date 30/11/2009) enclosed copy Annexure 1.
REFERENCES:
1. Karthick M, Prince SMP. Preventive effect of rutin, a bioflavonoid lipid peroxides
and antioxidants in isoproterenol-induced myocardial infarction in rats.
J Pharm Pharmacol 2006;58(5):701-7.
2. Thippeswamy BS, Thakker SP, Tubachi S, Kalyani GA, Netra MK, Patil U, et al.
. Cardioprotective Effect of Cucumis trigonus Roxb on isproterenol induced myocar-
dial infarction in rats. Am J Pharmacol Toxicol 2009;4(2):29-37.
3. Tripathi KD. Essential of Medical Pharmacology.5th ed. New Delhi: Jaype Brothers
Medical Publishers 2003:567-73.
4. Nivethetha M,Jayasri J, Brindha P. Effect of muntingia calabura L on isoproterenol
induced myocardial infarction. Singapore Med J 2009;50(3):300-2.
5. Vaidyaratnam PS. Editor. Indian medicinal plants.6th ed. Chennai: Orient Longman
Pvt. Ltd 2007;2:41-4.
6. Shinde UA, Kulkarni KR, Phadke AS, Nair AM, Mungantiwar AA, Dikshit VJ,
et al. Mast cell stabilizing and lipoxygenase inhibitory activity of Cedrus deodara
(Roxb) Loud.wood oil. Indian J Exp Biol 1999;37(3):258-61.
7. Kar K, Puri VN, Patnaik GK, Sur RN, Dhawan BN, Kulshrestha DK, et al.
Spasmolytic consitiuents of Cedrus deodara (Roxb) Loud: pharmacological eval-
uation of himachalol. J Pharm Sci 1975;64(2):258-62.
8. Tiwari AK, Srinivas PV, Kumar SP, Rao JM. Free radiacl scavenging active com-
ponents from Cedrus deodara. J Agric Food Chem 2001;49(10):4642-5.
9. Shinde UA, Phadke AS, Nair AM, Mungantiwar AA, Dikshit VJ, Saraf MN. Mem-
Brane stabilizing activity a possible mechanism of action for the anti-inflammatory
Activity of Cedrus deodara wood oil. Fitoterapia 1999;70(3):251-7.
10. Shinde UA, Phadke AS, Nair AM, Mungantiwar AA, Dikshit VJ, Saraf MN.
Preliminary studies on immunomodulatory activity of Cedrus deodara wood oil.
Fitoterapia 1999;70(4):333-9.
11. Vishwanath GL, Nandhakumar K, Shylaja H, Ramesh C, Rajesh S, Srinath R.
Anxiolytic and anticonvulsant activity of alcoholic extract of heartwood of
Cedrus deodara Roxb in rodents. JPRHC 2009;1(2):217-39.
12. Cedrus deodara [online].2006 may 12 [cited 2009 Nov 23]. Available from:URL
http://en.wikipedia.org/wiki/ Cedrus_ deodara.
13. Anonymous. The Wealth of India, publication and information directorate.
Council of Scientific and Industrial Research, New Delhi.1992;3:400-8.
9 / SIGNATURE OF THE CANDIDATE
10 / REMARK OF THE GUIDE:
The above information and literature has been extensively investigated, verified and is found to be correct. The present study will be carried out under my supervision and guidance.
11 / 11.1 NAME AND
DESIGNATION
OF GUIDE / Mr. Syed Mansoor Ahamed. M. Pharm., (Ph. D).
Assistant Professor
Department of Pharmacology
Sree Siddaganga College of Pharmacy,
B.H.Road, Tumkur - 572 102.
11.2 SIGNATURE
11.3 CO-GUIDE / N A
11.4 SIGNATURE / N A
12 / 12.1 HEAD OF THE
DEPARTMENT / Dr. Thippeswamy B S. M.Pharm.,Ph. D.
Professor and Head,
Department of Pharmacology
Sree Siddaganga College of Pharmacy,
B.H.Road, Tumkur - 572 102.
12.2 SIGNATURE
13 / 13.1 REMARKS OF
CHAIRMAN AND
PRINCIPAL / The above mentioned information is correct and
I recommend the same for approval.
13.2 SIGNATURE / Dr. S. Badami, M.Pharm.,Ph. D.
Principal and Director
Sree Siddaganga College of Pharmacy,
B.H.Road, Tumkur - 572 102.
11