Introduction to Ayurveda-Safety Aspects of Herbo-Metallic Compounds-Rasa Aushadhi of Ayurveda

1. Introduction to Ayurveda-Safety Aspects of Herbo-Metallic Compounds-Rasa Aushadhi of Ayurveda Prof. G.P. Dubey, Dr. Aruna Agrawal, Prof. G.V. Rajamanickam Centre for psychosomatic & Biofeedback Medicine & Deptt. Of Basic Principles, Faculty of Ayurveda, IMS, BHU & Centre for Advanced Research in Indian System of Medicine, SASTRA, Thanjavur

2. Ayurvedic approach of Health Ayurveda is a name which the Ancient Indians gave to their science of medicine. Ayuh means life and Veda means knowledge. Therefore Ayurveda is a science by the knowledge of which life can be prolonged and its nature can be understood. In a broader sense, Ayurveda like Dharma (religion) is not decompartmentalized; it includes the adaptation of customs, traditions, ethics, hygiene and medicine.

3. Subject Matter: The fundamental concept is mainly based on Samkhya and Nayaya Vaisheshika system of Indian philosophy. Subject matter is scattered in Vedas, Upanishads and other Classical literature. Charaka Samhita, Sushruta Samhita and Ashtanga Samgrah are three important Medical Texts.

4. Doshas are two types - Manasik (Psychic) – Sattva, Raja & Tama Sharirika (Somatic) – Vata, Pitta & Kapha Sharirika and Mansika dosas are interacting each other therefore, psychosomatic interaction is responsible for maintenance of physiological homeostasis. Ayurvedic concept of Health is based on Tridosha Theory. Tridosa is biological entity responsible for structural, functional and behavioral dimensions of the living organism.

5. MIND BODY INTERACTION Geographical Environment S R T P V K Socio Cultural Environment

6. SIGNIFICANCE OF PRAKRITI IN CLINICAL MEDICINE 1) Promotive Health 2) Preventive Health a) Clinical application of constitution study (Prakriti) b) Identification of Risk Factors c) Course, Complication and Ultimate prognosis of the disease. d)Drug body interaction

7. FACTORS RESPONSIBLE FOR HEALTH AND DISEASE 1) Society at risk a) Rural urban differences b) Economic status c) Education & Profession 2) Family at risk a) Structure of Family b) Familial diseases c) Social stress (marital tension , Strained inter- personal relationship, Poor religious affiliation ) 3)Individual at risk a) Psychosomatic constitution b) Individual habits

8. Ayurvedic approach of therapy • Promotive • Preventive • Curative • Non-Pharmacologic procedures: Diet, exercise, yogic-meditation relaxation practices, observance of sadvritta (socio-cultural conduct) as per doshik setup, and circadian and seasonal variation.

9. ii. Pharmacologic: plant based single and poly herbal preparations. Herbo-metallic preparations: Bhasma: Powder of a substance obtained by calcination is called Bhasmas. It is applied to metals and minerals and animal products Rasa-Yoga: Preparations containing minerals as main ingredients are called Rasa-yoga. Abhrak (Mica), Makshik (copper-pyrites) , Swarna (gold), Rajat (silver), Tamra (copper), Kamsya (Bell metal) etc. Rasa Aushadhi: Preparations containing metals, minerals are considered rasa-aushadhi:

10. Mercury, Arsenic, Lead, Zinc, Tin, Iron, Sulphur & Copper are mainly utilized for the preparation of Ayurvedic formulations. Metals are generally toxic in its native form. Several methods have been described for detoxification of metals & minerals in classical literature of Ayurveda. Documentation of the classical preparation along with their ingredients including history of use. Identification of new compound (herbo-metallic) showing therapeutic efficacy. Standardization of classical procedure by following objective parameters. Biological standardization of the product along with evaluation of safety and efficacy profile.

11. Physico-chemical characterizationDistribution, Bio-transformation and Elimination Route of Absorption : Inhalation of Vapor, sub- cutaneous and oral. Distribution : Distributes widely to all tissue, kidney, liver spleen and CNS. Elimination : Primarily by Urine and fecal Interact with different enzyme systems in the body in Presence of sulphur. Action : Target organ system

12. WHO LimitNormal permissible concentration

13. Normal and obtained level of elements in blood and urine

14. Experimental Animal Study Dose of Makardhwaj Makardhwaj: (i) 50 mg/kg daily Preparation of Makardhwaj as per classical method (Rasa Tarangini ) human dose 125mg to 250mg/day Gold - 1 part Mercury - 4 part Sulphur - 8 part Maximum Human Dose= 250mg/day ; Average Human Wt=50kg Per Kg Dose=250/50=5mg ; Animal Dose ten Times more

15. ACUTE TOXICITY OF MAKARDHWAJ Animal model - Charles foster strain rats No lethality was found at the highest dose of 300mg/kg/day

16. Neurobehavioral toxicity following Makardhwaj(Dose 50 mg/kg) No neurobehavioral abnormality was observed following oral administration of Makardhwaj

17. Chronic Toxicity of Makardhwaj: Chronic toxicity of studies were carried out among albino rabbits of Holland strain with average body weight of 1.86±0.58kg upto 3 months. The dose of Makardhwaj was 50mg/kg/day No adverse effect on hemopoetic, Gastro-intestinal, Hepatic & kidney function test were noticed.

18. Normal Micro angiography of the Kidney Right Kidney Left Kidney

19. HgCl2 2.5 mg/kg body wt; Makardhwaj 12.50 mg/kg body wt Dose 2.5 mg/kgbody wt Dose 5.0 mg/kgbody wt Damage with HgCl2 (Low Dose) Damage with HgCl2 (High Dose) Makardhwaj +HgCl2

20. Effect of Makardhwaj on serotonin level in experimental rats *vs** P>0.05 P>0.05 P>0.05 P>0.05 *vs*** P<0.01 P<0.001 P<0.001 P<0.001

21. Beneficial effect of Makardhwaj on nor-adrenaline in experimental rats *vs** P>0.05 P>0.05 P>0.05 P>0.05 *vs*** P<0.01 P<0.001 P<0.001 P<0.001

22. Effect of Makardhwaj on Dopamine level in experimental rats *vs** P>0.05 P>0.05 P>0.05 P>0.05 *vs*** P<0.001 P<0.001 P<0.001 P<0.001

23. Effect of Makardhwaj on choline- acetyl-transferase in experimental rats *vs** P>0.05 P>0.05 P>0.05 P>0.05 *vs*** P<0.001 P<0.001 P<0.001 P<0.001

24. Mahayograj guggulu (with silver & makardhwaj) is an Ayurvedic herbo - metallic preparation mainly advocated in the management of Rheumatoid and Osteo-arthritis. Heavy Metals µg/gm of the product (JAMA) (SASTRA & BHU) Lead : 37000 22000 Mercury : 22800 23800 Arsenic : 8100 6200 Presence of Organic materials

25. Mahayogaraj Guggulu (with Silver and Makardhwaj) Silver particle MET. ENGG. IT- BHU & SASTRA, THANJAVUR

26. Sem of Mahayograj guggul (with silver and Makardhwaj) Tubular particles Flakes Fused & Solidification cracks Fine Spherical particles Particles sizes varies from 2-100 microns

27. Acute toxicity of Mahayograj guggulu (with silver & Makardhwaj) Animal model: Charles Foester Strain rats.

28. Neurobehavioural acute toxicity following Mahayograj Guggulu (with Silver & Makardhwaj)(Dose 250 mg/kgbody wt)

29. Chronic Toxicity of Mahayograj Guggulu (with silver & Makardhwaj) Chronic toxicity of studies were carried out among albino rabbits of Holland strain with average body weight of 1.90±0.55kg upto 3 months. The dose of Mahayograj Guggulu (with silver & Makardhwaj) was 250mg/kg/day No adverse effects on hemopoetic Gastro-intestinal, Hepatict and kidney function test were noticed.

30. Changes in Acetylcholine concentration following oral administration of Mahalaxmivilas ras with gold mahayograj guggulu with gold & Mahayograj guggulu with silver & makardhwaj

31. Changes in nor-adrenaline following oral administration of Mahalaxmivilas ras with gold mahayograj guggulu with gold & Mahayograj guggulu with silver & makardhwaj

32. Changes in Dopamine following oral administration of Mahalaxmivilas ras with gold mahayograj guggulu with gold & Mahayograj guggulu with silver & makardhwaj

33. Clinical Study Procedure: 27 cases (14 male & 13 female) receiving Mahayogaraj Guggulu with silver & Makardhwaj in the dose of 2 tab twice in a day prescribed by qualified Ayurvedic physicians were selected. The cases receiving the therapy were carefully monitored for adverse reaction on different system. Three successive follow-up studies were carried out.

34. Toxicity studies of the subjects Evaluation of Mahayograj guggulu (with silver & Makardhwaj) on Hemopoetic system among rheumatoid arthritis cases.

35. Evaluation of Mahayograj guggulu (with silver & Makardhwaj) on Liver function tests among rheumatoid arthritis cases.

36. Evaluation of Mahayograj guggulu (with silver & makardhwaj) on Renal function tests among rheumatoid arthritis cases. ml/minute

37. Level of lead in blood and urine following oral administration of Mahayograj guggulu (with silver & makardhwaj) in rheumatoid arthritis cases g/dl Normal range – In Blood <29 gm/dl In Urine < 2.3 gm/dl

38. Level of mercury in blood and urine following oral administration of Mahayograj guggulu (with silver & makardhwaj) in rheumatoid arthritis cases g/dl Normal range – In Blood < 2.0 gm/dl In Urine < 2.3 gm/dl

39. Level of Arsenic in blood and urine following oral administration of Mahayograj guggulu (with silver & makardhwaj) in rheumatoid arthritis cases g/dl Normal range – In Blood < 3.0 gm/dl In Urine < 8.4 gm/dl

40. Elimination of lead after withdrawal of Mahayograj guggulu with silver and makardhwaj :- gm/dl

41. Conclusion • Ayurveda has adopted holistic approach. It includes the entire spectrum of life. • The object is to enhance longevity. • The application of fundamental principles of Ayurveda is helpful in the prevention and management of various mental and physical disorders. • The non-pharmacologic procedures include observance of good conduct and practice of relaxation, meditation and other yogic practices in order to maintain the positive health. • In Ayurveda various metal and minerals are used for the prevention and management of various diseases. The metals are modified in a new compound which have therapeutic potentials.

42. Thank you!