“ Recent Advances in Experimental Medicine” ( Focus on areas for possible convergence )

1. Conference on Healthy Gujarat- “Agenda for Actions”December 3rd , 2013Dept of Health and FW – Govt of GujaratGandhinagar “ Recent Advances in Experimental Medicine” ( Focus on areas for possible convergence ) Dr.B.Ravishankar SDM Centre for Research in Ayurveda and Allied Sciences Udupi Gandhinagar Dept of HFW- Dec 3rd 2013

2. Why convergence or integration is requited ? None of the existing systems can meet all the requirements of health care- existence of ‘ therapeutic gap’ Different systems work on different Scientific paradigms- Example – unitary or reductionists approach of conventional medicine Holistic approaches of ISM like Ayurveda – combining the approaches may be beneficial Unique mechanisms of action - possible benefits - through synergestic therapy Patients acceptability and preference high for integrated approach Gandhinagar Dept of HFW- Dec 3rd 2013

3. Potential areas of convergence : Prophylaxis Diagnosis Drug therapy Combination of non-drug therapies and drugs Requirement : Data generation as Evidence base through experimental studies- both basic and clinical Gandhinagar Dept of HFW- Dec 3rd 2013

4. Prophylaxis- Concepts of proper daily, seasonal routines advocated in Ayurveda can be integrated Constitution types – similar to genomic studies – ex- 1 Functional Foods- Prophylactic measures in ISM Avoidance of incompatibilities – adoption of the concept of incompatibilities Drug research- the fundamental concept for drug selection and incorporation to therapeutics is known as Rasapanchaka . < Rasa < Guna < Veerya < Vipaka and Prabhava are the five attributes considered in candidate plant or formulations . Interesting recent developments – related to rasapanchaka Gandhinagar Dept of HFW- Dec 3rd 2013

5. Drug related incompatibilities: Incompatibility of climate, season and soil- (desa- and kala viruddha) – Incompatibility of drug preparation-(Samskara- viruddha) Arrangement of order of drug administration - (krama) Drug preparation method (Paka) Physical and chemical factors (Samyoga) Quantitative (mana-virodha)- ghee and honey taken in equal quantity Qualitative- (karma virodha)- dhataki and danti Gandhinagar Dept of HFW- Dec 3rd 2013

6. Combined drug therapy B kalpana- the science of formulation in ayurveda is highly sophisticated and formulation factors have tremendous influence over the expression of the biological activity. > 22 types of formulation forms are in vogue Gandhinagar Dept of HFW- Dec 3rd 2013

7. Drug action through bio-enhancement (Trikatu): The mechanism of drug bioavailability enhancing effect of Piperine: a-increased blood supply to the gastrointestinal tract, b- increased enzymatic activities like gamma-glutamyl transpeptidase which participates in active transport of nutrients across the intestinal cells   c- non-specific mechanisms inhibiting enzymes involving in biotransformation of drugs, preventing their inactivation and elimination (Goldstein, 1984; Esposito, 1984) d- by increasing the membrane fluidity - Piperine, or mixtures containing piperine, has been shown to increase the bioavailability, blood levels and efficacy of a number of drugs including ingredients of vasaka leaves, vasicine, sparteine, sulfadiazine, rifampicin, phenytoin and propranolol Gandhinagar Dept of HFW- Dec 3rd 2013

8. AS adjuvant Cyclo –Immunosuppression- Table-A and Fig-A Cyclo-myelosuppression- Table-B Table- A – Effect of VDAV and ADJ on Cyclophosphamide induced suprression of anti-SRBC antibody in rats/ Gandhinagar Dept of HFW- Dec 3rd 2013

9. Effect on fasting blood sugar Disease control Jasad bhasma Jasad +Betle Lipoic acid Normal control Courtesy Dr. Supriya Bhale Rao Gandhinagar Dept of HFW- Dec 3rd 2013

10. Effect on nerve conduction velocity Normal control Lipoic acid Jasad + Betle Jasad bhasma Disease control Gandhinagar Dept of HFW- Dec 3rd 2013

11. Bacopa and Centella extracts increase neuronal branching -Paper 1 Net work and System pharmacology concepts Example-1 Result a new discipline Quantitative and Systemic Pharmacology-An NIH White Paper by the QSP Workshop Group – October, 2011 Gandhinagar Dept of HFW- Dec 3rd 2013

12. Examples of unique mechanisms of action of Ayu drugs Gandhinagar Dept of HFW- Dec 3rd 2013

13. Modulation of nuclear receptors : Guggulsterone- antagonizes the farnesoid X receptor (FXR), which regulates cholesterol metabolism in the liver Guggulsterones also modulate the activity of multiple nuclear receptors- involved in steroid hormone regulation- glucocorticoid, progesterone , mineralocorticoid, androgen and estrogen receptors Guggulsterone up-regulates the bile salt export pump (BSEP- favours metabolism of cholesterol to bile acids The cembranoids (from guggul) lowered the cholate (1)- activated rate of human pancreatic-IB phospholipase A2 (hPLA2), which controls gastrointestinal absorption of fat and cholesterol Gandhinagar Dept of HFW- Dec 3rd 2013

14. Multimodal mechanism of action- Gandhinagar Dept of HFW- Dec 3rd 2013

15. Multimodal mechanism of action- 3 ( Effect on networks) FIG 1. Targets of curcumin. Abbreviations: MEKK, MAPK/ERK kinase kinase; IKK, IB kinase; IB, inhibitory kappa B; CBP, CREB-binding protein; HDAC, histone deacetylase; P, phosphorylation; U, ubiquitination; MAPK, mitogen activated protein kinase; MEK, MAPK/ERK kinase; MKK, MEK kinase; ERK, extracellular signal regulated kinase; JNK, cJun N-terminal kinase; TAK/ASK, transforming growth factor--activated /apoptosis signal-regulated kinase; PI3K, phosphatidylinositol-3-kinase; ISRE, IFN-stimulated responsive element; GAS, IFN activation site; mTOR Mammalian target of rapamycin; PKC, protein kinase C; Keap, Kelch-like ECH-associated protein 1. (Color version of figure is available online.) Gandhinagar Dept of HFW- Dec 3rd 2013

16. Effect on Epigenetic factors From : Simone Reuter • Subash C. Gupta • Byoungduck Park • Ajay Goel • Bharat B. Aggarwal. Epigenetic changes induced by curcumin and other natural compounds. Genes Nutr (2011) 6:93–108. DOI 10.1007/s12263-011-0222-1 Gandhinagar Dept of HFW- Dec 3rd 2013

17. Synergistic pharmacology : Synergy research: approaching a new generation of phytopharmaceuticals-H. Wagner G. Ulrich-Merzenich Two events initiated synergy research in phytomedicine: first, the new methods of analytical chemistry and molecular biology that have become available during the past decade, and second, an unexpected change of paradigm in chemotherapy that appeared without great attention Multidrug therapy is already being practiced worldwide in the treatment of AIDS and other infectious diseases, hypertension, numerous types of cancer and rheumatic diseases Gandhinagar Dept of HFW- Dec 3rd 2013

18. Review on herb drug interactions Drug transporters are now widely acknowledged as important determinants governing drug absorption, excretion, and, in many cases, extent of drug entry into target organs Examples of drug transporter modulators from plants- curcumin, piperine, silymarin, ginsenosides, catechin and flavonoids etc Can be an important target for drug formulation development Gandhinagar Dept of HFW- Dec 3rd 2013

19. From the above facts it becomes clear that data generation through experimental (research) studies are the first requisite to identify the potential areas for convergence of conventional and Traditional medical systems Thus there is urgent requirement for the establishment of dedicated research and innovation centres in the field of Ayurveda and Integrative Medicine Establishment of ISM Innovation and Research Universities would be a welcome initiative Legislation for dual or multiple medical practice licence is also required Gandhinagar Dept of HFW- Dec 3rd 2013

20. Thank you Gandhinagar Dept of HFW- Dec 3rd 2013