Study of Analgesic, Anti-Inflammatory and Antiarthritic Activity of Indian Medicinal Plant in Laboratory Animals
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STUDY OF ANALGESIC, ANTI-INFLAMMATORY AND ANTIARTHRITIC ACTIVITY OF INDIAN MEDICINAL PLANT IN LABORATORY ANIMALS A THESIS SUBMITTED TO BHARATI VIDYAPEETH UNIVERSITY, PUNE FOR AWARD OF DEGREE OF DOCTOR OF PHILOSOPHY IN PHARMACOLOGY UNDER THE FACULTY OF PHARMACEUTICAL SCIENCES SUBMITTED BY Mr. GOPAL V. BIHANI M.Pharm UNDER THE GUIDANCE OF Dr. SUBHASH L. BODHANKAR RESEARCH CENTRE BHARATI VIDYAPEETH DEEMED UNIVERSITY, POONA COLLEGE OF PHARMACY, ERANDWANE, PUNE- 411 038, INDIA FEBRUARY 2016 CERTIFICATE This is to certify that the work incorporated in the thesis entitled “Study of Analgesic, Anti-inflammatory and Antiarthritic activity of Indian medicinal plant in laboratory animals” for the degree of ‘Doctor of Philosophy’ in the subject of Pharmacology under the faculty of Pharmaceutical sciences has been carried out by Mr. Gopal Vijaykumar Bihani in the Department of Pharmacology, Bharati Vidyapeeth Deemed University, Poona College of Pharmacy, Pune during the period from November 2012 to January 2016, under the guidance of Dr. S. L. Bodhankar, Professor and Head, Department of Pharmacology, Poona College of Pharmacy, Pune. Place: Pune Date: Prof. K. R. Mahadik Professor and Principal Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Pune - 411038 CERTIFICATE This is to certify that the work incorporated in the thesis entitled “Study of Analgesic, Anti-inflammatory and Antiarthritic activity of Indian medicinal plant in laboratory animals” Submitted by Mr. Gopal Vijaykumar Bihani for the degree of ‘Doctor of Philosophy’ in the subject of Pharmacology under the faculty of Pharmaceutical sciences has been carried out in the Department of Pharmacology, Bharati Vidyapeeth Deemed University, Poona College of Pharmacy, Pune during the period from November 2012 to January 2016, under my direct supervision/guidance. Place: Pune Date: Dr. S. L. Bodhankar Professor and Head Dept. of Pharmacology Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Pune - 411038 DECLARATION BY THE CANDITATE I hereby declare that the thesis entitled “Study of Analgesic, Anti-inflammatory and Antiarthritic activity of Indian medicinal plant in laboratory animals” submitted by me to the Bharati Vidyapeeth University, Pune for the degree of Doctor of Philosophy (Ph.D.) in Pharmacology under the faculty of “Pharmaceutical Sciences” is original piece of work carried out by me under the supervision of Dr. S. L. Bodhankar. I further declare that it has not been submitted to this or any other university or institution for the award of any degree or diploma. I also confirm that all the material which I have borrowed from other sources and incorporated in this thesis is duly acknowledged. If any material is not duly acknowledged and found incorporated in this thesis, it is entirely my responsibility. I am fully aware of the implications of any such act which might have been committed by me advertently or inadvertently. Place: Pune Date: Mr. Gopal V. Bihani Research student Acknowledgement AAACKNOWLEDGEMENTACKNOWLEDGEMENT The path from dreams to success does exist, may you have the vision to find it, the courage to get on to it. A journey is easier when you travel together. Interdependence is certainly more valuable than independence. This thesis is the result of three years of work whereby I have been accompanied and supported by many people. It is a pleasant aspect that I have now the opportunity to express my gratitude for all of them. This thesis would not appear in its present form without the kind assistance and support of the following individuals and organizations. I thank the almighty for showering infinite bounties and grace upon me and for being my constant companion. I am thankful to our Vice-Chancellor Dr. S. S. KadamKadam and Principal Dr. K. R. Mahadik for providing proper resources and infrastructure to carry out the work of this stature. I would like to thank my Guide Dr. S. L. Bodhankar, the best advisor and guide I could have wished for. During these years I have known him as a sympathetic and principle-centered person. Their enthusiasm and integral view on research and mission for providing 'only high-quality work and not less', has made a deep impression on me. I owe him lots of gratitude for having me shown this way of research. He taught me to look for solutions to problems rather than focus on the problem. I learned to believe in my future, my work and myself only because of him. I am deeply indebted to Dr. S. R. RojatkarRojatkar, Director, R & D centre for Pharmaceutical Sciences and Applied chemistry, Pune for extended support, encouragement and fruitful discussion during execution of this work. It is my pleasant duty to thank, extending a helping hand and supporting me throughout my research work. A special thanks to Dr. P. R. RajRajaaaamohanan,mohanan, Head NMR Acknowledgement facility group and Dr. K. B. SonawSonawane,ane, Scientist E1, Dept. of Organic Chemistry, National Chemical Laboratory, Pune for his help in generating valuable data during research work. I wish to express my sincere and respectful thanks to Dr. A. P. Pawar, Dean and Vice Principal, Bharati Vidyapeeth Deemed University, Poona College of Pharmacy and Mr. G. N. ZambareZambare, Dr. Arulmozhi and Dr. Balasaheb Siraskar for their constant support and valuable suggestions. I would also like to thank Dr. Suryawanshi for his timely suggestions. It is said that ‘accomplishment must be credited to those who have put up the foundation of the particular chore’. I would like to thank my parents, Mummy and Papa who were always ready to help me at all times now I can only show you my extreme appreciation for your support by being true to all the ideals and values that you tried to teach me thank you forever and standing by me, I love and appreciate you forever. Also I would like to thank my bbbrotherbrother Mr. Radheshyam and bhabhi Mrs. Trupti for their parent like care and blessings have driven my performance and success. Their support has helped me to complete this work successfully. Also I thank my beloved cute niece Sachi and nephew Swarit for the laughter gifted to me with their cute and tender voice. Also thanks to my wife Renuka you have been a never-ending source of love, encouragement and motivation. I look forward to our lifelong journey. It would be unfair if I don’t mention the help showered on me by my senior and friend DDDr.Dr. Parag Kadam. I sincerely thank and express my profound gratitude towards him for providing invaluable insight. It gives me immense pleasure to express my thanks to my colleagues and seniors Dr. Vishal Mali, Dr. Smeeta Mohod, DDDr.Dr. Hemant Kamble, Mr. Sameer Sawant, Mr. Amit Kandhare, Mr. Amol Muthal, andandand Mrs. Bhagyshri Atre who believed in constantly motivating me and supported me in achieving my goals. I am also thankful to my other department colleagues DDDr.Dr. Ashwin Kuchekar, DDDr.Dr. Sujit Acknowledgement Bhansali, Dr. Prashant Bhondave, Mr. Vijay Kale, Mr. Pravin Pawar, Mr. Prakash Jadhav, Mr. Sumit DeoDeore,re, Mrs. Anjali, Mrs. Sampada Sawant and Mrs. Sabina. I am also thankful to Botanical Survey of IndiaIndia, Pune, for extending help in getting my plant authenticated. I am also thankful to Dhande laboratorylaboratory, Pune for interpretation of histopathological data. I would like to thank Mr. BBhhhhatlekaratlekaratlekar, Incharge, National Institute of Biosciences Pune for providing animals towards this project. I am thankful to all non-teaching staff especially Mr. D. J. Joshi for extending help and cooperation. I am deeply indebted to all animals whose lives were sacrificed during this research work. I hope that precious life of the animals used during this project would not be in vain; it would contribute to the development of the science in one way or another. Beside this there are several other people who have knowingly or unknowingly helped me in the successful completion of this project. I thank all the people for every ounce of efforts they contributed. Date: Place: Pune Mr. Gopal V. Bihani Dedicated to my Beloved Family, Guide & God INDEX INDEX Title Page No. Title page Certificate of Principal Certificate of Guide Declaration Acknowledgement Index Contents List of Tables List of Figures List of Abbreviations Chapter 1 Introduction 01 – 06 Chapter 2 Review of Literature 07 – 71 Chapter 3 Aims and Objectives 72 – 73 Chapter 4 Materials and Methods 74 – 107 Chapter 5 Results 108 – 228 Chapter 6 Discussion 229 – 241 Chapter 7 Summary and Conclusion 242 – 247 Chapter 8 Highlights of the work 248 – 253 Chapter 9 Bibliography 254 – 267 Chapter 10 Publications 268 Errata 269 – 271 INDEX CONTENTS Chapter 1 Introduction 01 – 06 Chapter 2 Review of literature 07 – 71 2.1 Inflammation 07 – 35 2.1.1 Definition and causes 07 2.1.2 Signs of inflammation 07 2.1.3 Types of inflammation 08 2.1.4 Chemical mediators of inflammation 20 2.1.5 Regulation of inflammation 26 2.1.6 Inflammatory cells 27 2.1.7 Pre-clinical screening methods for anti-inflammatory agents 30 (In vivo methods) 2.1.8 Plants reported to have anti-inflammatory activity 33 2.2 Arthritis: Historical Background & Epidemiology 36 – 66 2.2.1 Rheumatoid arthritis (RA) 37 2.2.2 Epidemiology and Etiology 37 2.2.3 Pathophysiology 38 2.2.4 Comorbidities associated with RA 40 2.2.5 Clinical manifestations 41 2.2.6 Diagnosis 42 2.2.7 Investigations 43 2.2.8 Pre-clinical screening methods for antiarthritic agents (In vivo 44 methods) 2.2.9 Treatment 48 2.2.10 RA and pregnancy 65 2.3 Cyathocline purpurea (Buch-Ham ex D. Don.) Kuntze 67 – 71 2.3.1 Taxonomic Classification 67 2.3.2 Botanical description and Vernacular name 67 2.3.3 Morphology 68 2.3.4 Occurrence and Distribution 68 INDEX 2.3.5 Phytoconstituents 68 2.3.6 Pharmacological activities reported of Cyathocline purpurea 69 (Buch-Ham ex D.