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For the degree Master in pharmacy in Pharmacology

Presentation On Preclinical Evaluation of Tinospora cordifolia L . Bark Extract as Neuroprotective Agent for its application in CNS Cognition Studies . For the degree Master in pharmacy in Pharmacology PRESENTED BY

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For the degree Master in pharmacy in Pharmacology

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  1. Presentation On Preclinical Evaluation of Tinospora cordifolia L. Bark Extract as Neuroprotective Agent for its application in CNS Cognition Studies For the degree Master in pharmacy in Pharmacology PRESENTED BY Abhishek Joshi SUPERVISOR CO-SUPERVISOR DR.Mahendra Rana DR. A.K. Mishra (Assistant Professor) (HOD & Jt.Director) Department of Pharmaceutical sciences INMAS(DRDO) Bhimtal Campus, Kumaun University DELHI

  2. INTRODUCTION • Memory function is vulnerable to a variety of pathologic processes including neuro- degenerative diseases, hypoxia, attention-deficit disorder, depression, anxiety . • Learning and memory are generated by an experience dependent and long-lasting modification of the central nervous system. • They involve activation by neurotransmitters, such as, acetylcholine, dopamine, and serotonin, of the receptor-linked enzymes • A large number of studies shows that the cholinergic system plays an important role in learning and memory loss of cholinergic neurons

  3. Reduced choline- acetyltransferase activity in the cerebral cortex and hippocampus are consistent with findings in Neurodegenerative disorder(ND) . • Reduced cholinergic activity in the brains of individuals with ND provides the rationale for the development of acetyl cholinesterase (AChE) inhibitors to treat ND. • NEUROTRANSMITTERS • Neurotransmitters are chemicals that transmit information from one nerve cell (neuron) to another. “They are defined as chemical transducers which are released by electrical impulse into the synaptic cleft from presynaptic membrane from synaptic vesicles. It then diffuses to the postsynaptic membrane and reacts and activates the receptors present leading to initiation of new electrical signals.”

  4. PLANT UNDER STUDY • PLANT PROFILE • Tinospora cordifolia, which is known by the common name Guduchi, is a herbaceous wine of the family Menispermaceae indigenous to the tropical areas of India, Myanmar and Sri lanka. The plant is a glabrous climbing shrub found throughout India, typically growing in deciduous and dry forests. • Tinospora cordifolia has greenish flowers, fruits are shiny fleshy, pea shaped, which occurs in winters and the entire plant is used medicinally. • Taxonomical classification • Kingdom: Plantae • Division: Magnoliophyta • Class: Magnoliopsida • Order: Ranunculales • Family: Menispermaceae • Genus: Tinospora • Species: cordifolia • Synonym: Hindi: giloe, Sanskrit: Amritavalli, Marathi: Guduchi , • Binomial name: - Tinospora cordifolia

  5. Ethno-Pharmacological uses/actions: • Anti-diabetic • Anti-inflammatory • Anti-arthritic • Anti-oxidant • Anti-allergic • Anti-stress • Anti-malarial • Hepatoprotective • Anti-neoplastic activities

  6. AIM AND OBJECTIVE Aim: The aim of the investigation is radiolabelling of Tinospora cordifolia bark extract and evaluating its neuroprotective agent for application in CNS cognition studies. 1. Preliminary investigation carried out determining the ability of selected doses of a plant bark extract. 2. The test material subjected to various parameters like optimization of labeling conditions, quality control, PH Study parameter, drug- stability, blood-kinetics and bio-distribution studies. Objectives: The principle objective of study:- • Alteration in neurotransmitters level in pre-treated (Irradiation treated) mice. • Alteration in neurotransmitters level in post-treated(Irradiation+ Extract treated) mice.

  7. LITERATURE REVIEW

  8. WORK DONE • 1.Tinospora cordifolia barks were collected from the hilly region of Uttarakhand. • 2. The extraction of the bark sample was done under the guidance and supervision of Dr. Hemant Kumar Pande(DIBER,Pithoragarh). • 3. The extract obtained was then evaluated for the presence of active constituentspresent in it. • 4. The extract was radiolabelled with technetium-99m. • 5. The radiolabelling efficiency of the extract was evaluated. • 6.The radiolabelled herbal extract was injected to female mice and radiolabelling Studies were performed. • 7.Pharmacokinetics Study of herbal extract was performed and drug clearance rate was identified.

  9. PROPOSED PLANS In Vitro Animal Studies Comparative Study Of Radiolabelled Herbal Extract With Standard Drug(Piracetam) Brain Uptake Studies Bio Distribution(Organ) Studies.

  10. REFERENCES 1.Upadhyaya R., Pandey R.P., Sharma V. and Verma Anita K., assessment of the multifaceted immuno modulatory potential of the aqueous extract of Tinospora cordifolia, Research Journal of Chemical Sciences; 2011, 1(6), 71-76 2.Nasreen S.,R Radha. and N Jayashree., assesment of quality of Tinospora cordifolia (Willd.) miers. (Menispermaceae) pharmacognostical and phytophysiochemical profile, International Journal Of Comprehensive Pharmacy; 2010, 1(5), 113-117 3.Upadhyay A K., Kumar K., Kumar A. and Mishra H S; Tinospora cordifolia (Willd.) Hook. f. and Thoms. (Guduchi) - validation of the ayurvedic pharmacology through experimental and clinical studies, International Journal of Ayurveda Research; 2010, 1(2), 112-121.

  11. 4.Demma J, Engidawork E. and Hellman B., potential genotoxicity of plant extracts used in Ethiopian traditional medicine, J Ethnopharmacol; 2009, 1(12), 136- 142. • 5.Chaudhary R.,Jahan S. and Goyal P.K., chemopreventive potential of an Indian medicinal plant (Tinospora cordifolia) on skin carcinogenesis in mice, Journal of Environment Pathology Toxicology Oncology., 2008, 3(27), 233-243. • 6. Kapur P., Pereira B.M., Wuttke W. and Jarry H., androgenic action of Tinospora cordifolia ethanolic extract in prostate cancer Cell line LNCaP, Phytomedicine, 2008, 16(6), 679-682 • 7.Barthwal J., Nair S. and Kakkar P., Heavy metal accumulation in medicinal plants collected from environmentally different sites, Biomed Environ Sci., 2008, 21(4), 319-324 • 8. Rao S.K., Rao P.S. and Rao B.N., Preliminary investigation of the radio-sensitizing activity of guduchi (Tinospora cordifolia) in tumor bearing mice , Phytother Res., 2008 , 22(11), 1482-1489 .

  12. 9.Lohar D R and Singh R; Quality Control Manual for Ayurvedic, Siddha and UnaniMedicine. Ghaziabad: Department of Ayush, Ministry of Health and Family Welfare, Pharmacopoeial Laboratory for Indian Medicine;2008, 1(6), 21-24. • 10.Amirghofran Z., Azadmehr A., and Javidnia K., Haussknechtia elymatica: A plant with immunomodulatory effects, Iran Journal of Immunology., (2007), 11(3), 126-131. • 11.Bairy KL, Rao Y., efficacy of Tinospora cordifolia on learning and memory in healthy volunteers A double blind, randomized, placebo controlled study, Iranian Journal of pharmacol Therapy., 2004, 3(1), 57-60. • 12.Anonymous; The Ayurvedic Pharmacopoeia Of India, New Delhi Department of Ayush, Ministry Of Health And Family Welfare, Government of India.,2009, 4(2) ,70 – 72. • 13.Singh SS., Pandey SC. and Shrivastava S., Chemistry and medicinal Properties of Tinospora cordifolia, Indian J Pharmacol.,2003, 35(7), 83-89.

  13. 14. Jahfar M., Glycosyl composition of polysaccharide from Tinospora cordifolia , Acta Pharm., 2003 ,53(1), 65-69 • Subramanian M., Chintalwar G.J. and Chattopadhyay S., antioxidant properties of a Tinospora cordifolia polysaccharide against iron mediated lipid damage and gamma-ray induced protein damage, Redox Rep., 2002, 7(3), 137-143 • Jana U, Chattopadhyay RN. and Shaw BP., preliminary studies on anti inflammatory activity of Zingiber officinale Rosc., Vitex negundo Linn. and Tinospora cordifolia (Willid) Miers in albino rats, Indian J Pharmacol.,1999, 31(7), 232-233. • Mathew S. and Kuttan G.,antioxidant activity of Tinospora cordifolia and its usefulness in the amelioration of cyclophosphamide induced toxicity, J. Exp. Clin. Cancer Res., 1997, 16(4), 407-411. • Jain BG., Jain VK. and Shete A., antipsychotic activity of aqueous • ethanolic extract of Tinospora Cordifolia in amphetamine challenged mice model, J Adv Pharm Tech Res ,2010, 1(3), 30-33.

  14. Bairy KL,Rao Y et al., efficacy of Tinospora cordifolia on learning and memory in healthy volunteers: A double blind, randomized, placebo controlled study Iranian J pharmacol Therap, 2004; 3(1), 57-60 • Singh SS, Pandey SC, Shrivastava S, et al. Chemistry and medicinal properties of Tinospora cordifolia. Indian J Pharmacol. 2003; 35(1), 83-89. • 21. Jahfar M., Glycosyl composition of polysaccharide from Tinospora • cordifolia, Acta Pharm.,2002; 53(1), 65-69 • 22. Subramanian M., Chintalwar G.J., Chattopadhyay S., Antioxidant properties of Tinospora cordifolia polysaccharide against iron mediated lipid damage and gamma-ray induced protein damage, Redox Re • 2002; 7, 137-143 • 23. Jana U, Chattopadhyay RN, Shaw BP. Preliminary studies on anti • inflammatory activity of Zingiber offi cinale Rosc., Vitex negundo Linn.Tinospora cordifolia (Willid) Miers in albino rats. Indian J Pharmacol. 1999; 31(2), 232-233.

  15. 24. Mathew S. and Kuttan G.,antioxidant activity of Tinospora cordifolia and its Usefulness in the amelioration of cyclophosphamide induced toxicity, J. Exp. Clin. Cancer Res.,1997, 16(4), 407-411 • 25. Jain BG., Jain VK. and Shete A., antipsychotic activity of aqueous ethanolic extract of Tinospora cordifolia in amphetamine challenged mice model.J Adv Pharm Tech Res,2010, 1(3), 30-33. • 26. Singla A . and Singla P., review of biological activities of Tinospora cordifolia,webmed Central Pharmaceutical Sciences., 2010, 1(9), 1-5. • 27. Khosa RL, Sarma DNK, Ghanasauria JPN. and Ray AK., effect of • Tinospora cordifolia on brain neurotransmitter in stressed rats. Fitoterapia.,1995, 14(1) , 421. • 28. Goel H.C., Prasad J., Singh S., Sagar R.K., Agarwal P.K., Bala M., • Sinha A.K. and Dogra R., radioprotective potential of a herbal • extract of Tinospora cordifolia, J. Radiat. Res., 2004, 45(1), 61–68.

  16. 29. Singh SS., Pandey SC., Srivastava S., Gupta VS., Patro B. and Ghosh AC., Chemistry and medicinal properties of Tinospora cordifolia (Guduchi), Indian J Pharmacol., 2003, 35(1), 83–91 • 30. Parle Milind. and Dhingra D., ascorbic acid: a promising memory enhancer in mice, J. Pharmacol. Sci., 2003, 93(1), 129-135. • 31. Pahadiya S.and Sharma J., alteration of lethal effects of gamma rays in swiss albino mice by Tinospora cordifolia. Phytother. Res., 2003, 17(1), 552-554. • 32. PSM. and Menon VP., short communications: hypogycaemic • and hypolipidaemic action of alcohol extract of Tinospora cordifolia roots in chemical induced diabetes in rats, Phytotherapy Research., 2003, 17(1), 410-413. • 33.Agarwal A., Malini S., Bairy KL. and Rao MS., effect of Tinospora Cordifolia on learning and memory in normal and memory deficit rats, Indian J Pharmacol., 2002, 34(1), 339–349.

  17. 34.Bishayi B., Roychowdhury S., Ghosh S. and Sengupta M., hepatoprotective and immuno modulatory properties of Tinospora cordifolia in CCl4 intoxicated mature albino rats. J Toxicol Sci., 2002, 27(1),139–146. • 35.Pendse VK., Dadhich AP., Mathur PN., Bal MS., and Madam BR., anti-inflammatory, immunosuppressive and some related pharma cological actions of the water extract of Neem Giloe Tinospora cordifolia a preliminary report, Indian J Pharmacol., 1977, 9(1), 221–224. • 36. Kapil A, and Sharma S., immuno-potentiating compounds from • Tinospora cordifolia, J.Ethnopharmacol., 1997, 58(1) , 89-95.

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