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
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.
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.
Ayurvedic concept of Health is based on Tridosha Theory. Tridosa is biological entity responsible for structural, functional and behavioral dimensions of the living organism. 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.
MIND BODY INTERACTION S R T P V K
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
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 interpersonal relationship, Poor religious affiliation ) 3) Individual at risk a) Psychosomatic constitution b) Individual habits
Ayurvedic approach of therapy Promotive Preventive Curative i. Non-Pharmacologic procedures: Diet, exercise, yogic-meditation relaxation practices, observance of sadvritta (socio- cultural conduct) as per doshik setup, and circadian and seasonal variation.
ii. Pharmacologic: : plant based single and poly herbal preparations. ii. Pharmacologic 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) pyrites), Swarna (gold), Rajat (silver), Tamra (copper), Kamsya (Bell metal) etc. Rasa Aushadhi: Preparations containing metals, minerals are considered rasa-aushadhi aushadhi:
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( 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.
Physico-chemical chemical characterization Distribution, 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 in the body in Presence of sulphur. Action : Target organ system
WHO Limit Normal permissible concentration Heavy Metals Mercury 0.2-3 ng/ml Arsenic 1.1 µgm/lit. Blood Lead 0.02-1.0 µgm/lit. Copper 100-200 µgm/dl Aluminium 1-1010 ng/ml Nickel 0.05-1 ng/ml Magnisium 1.8-3 3 mg/dl Zinc 50-150 µgm/lit. Iron 50.175 µgm/lit.
Normal and obtained level of elements in blood and urine Element s Normal Value Blood (µg/dl) Obtained Value Urban Rural Normal Value Urine (µg/dl) Obtained Value Urban Rural Mercury 2.0 3.10 0.96 2.3 2.9 1.0 Lead 2.9 6.5 3.5 2.3 5.8 2.9 Arsenic 3.10 3.98 1.96 8.4 9.2 5.4
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
ACUTE TOXICITY OF MAKARDHWAJ Animal model - Charles foster strain rats Dose level (mg/ kg) Sample size Mortality after 24 hrs. 50 6 0/6 100 6 0/6 150 6 0/6 200 6 0/6 250 6 0/6 300 6 0/6 No lethality was found at the highest dose of 300mg/kg/day
Neurobehavioral toxicity following Makardhwaj (Dose 50 mg/kg) Tests Flexing reflex Initial After 6 hrs Observations After 12 hrs After 24 hrs + + + + Grasping + + + + Corneal reflex + + + + Equilibrium + + + + Head shaking + + + + Auditory + + + + No neurobehavioral abnormality was observed following oral administration of Makardhwaj
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.
Normal Micro angiography of the Kidney Right Kidney Left Kidney
Dose 2.5 mg/kg body wt Dose 5.0 mg/kg body wt HgCl 2 2.5 mg/kg body wt; Makardhwaj 12.50 mg/kg body wt Damage with HgCl 2 (Low Dose) Damage with HgCl 2 (High Dose) Makardhwaj +HgCl 2
Effect of Makardhwaj on serotonin level in experimental rats Treated Group Normal control (ACSF 5ml)* Makardhwaj 300 mg/kg ** Makardhwaj 100 mg/kg *** No. of animal 10 10 10 Serotonin (µ( gm/gm tissue) Frontal Cortex Hippocampus 7 days 14 days 7 days 14 days 0.422 ± 0.088 0.316 ±0.061 0.438 ±0.082 0.418 ± 0.075 0.364 ±0.054 0.456 ±0.072 0.362 ± 0.092 0.241 ±0.042 0.384 ±0.065 0.364 ± 0.084 0.201 ±0.064 0.396 ±0.075 *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
Beneficial effect of Makardhwaj on nor-adrenaline in experimental rats Treated Group Normal control (ACSF 5ml)* Makardhwaj 300 mg/kg ** Makardhwaj 100 mg/kg *** No. of animal 10 10 10 nor-adrenaline(µ gm/gm tissue) Total brain Mid brain 7 days 14 days 7 days 14 days 0.368 ±0.067 0.222 ±0.045 0.384 ±0.085 0.376 ± 0.058 0.216 ±0.051 0.388 ±0.078 0.621 ± 0.092 0.408 ±0.039 0.642 ±0.098 0.631 ± 0.085 0.402 ±0.061 0.650 ±0.090 *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
Effect of Makardhwaj on Dopamine level in experimental rats Dopamine (µ gm/gm tissue) Treated Group Normal control (ACSF 5ml)* Makardhwaj 300 mg/kg ** Makardhwaj 100 mg/kg *** No. of animal 10 10 10 Total brain Mid brain 7 days 14 days 7 days 14 days 0.836 ±0.082 0.664 ±0.050 0.841 ±0.101 0.842 ±0.074 0.641 ±0.033 0.858 ±0.104 1.272 ±0.092 1.156 ±0.024 1.289 ±0.088 1.208 ±0.088 1.108 ±0.052 1.283 ±0.098 *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
Effect of Makardhwaj on choline- acetyl-transferase transferase in experimental rats ChAT activity (n mol/mg protein/hour) Treated Group Normal control (ACSF 5ml)* Makardhwaj 300 mg/kg ** Makardhwaj 100 mg/kg *** No. of animal 10 10 10 Frontal cortex Hippocampus 7 days 14 days 7 days 14 days 22.34 ±2.85 18.21 ±2.01 24.14 ±3.02 23.97 ±3.11 16.14 ±2.11 25.68 ±2.94 20.24 ±2.12 16.22 ±3.01 21.98 ±3.94 19.88 ±2.75 14.06 ±3.10 23.42 ±4.82 *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
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
Mahayogaraj Guggulu (with Silver and Makardhwaj) Silver particle MET. ENGG. IT- BHU & SASTRA, THANJAVUR
Sem of Mahayograj guggul (with silver and Makardhwaj) Tubular particles Flakes Fine Spherical particles Fused & Solidification cracks Particles sizes varies from 2-100 microns
Acute toxicity of Mahayograj guggulu (with silver & Makardhwaj) Animal model: Charles Foester Strain rats. Dose Level (mg/kg body wt.) Sample Size Mortality after 72 hrs. 250 6 0/6 500 6 0/6 1000 6 0/6 1500 6 0/6 2000 6 0/6
Neurobehavioural acute toxicity following Mahayograj Guggulu (with Silver & Makardhwaj) (Dose 250 mg/kg body wt) Tests Flexing reflex Grasping reflex Corneal reflex Body equilibrium Head shaking Initial Observations After 24 hrs. After 48 hrs. After 72 hrs. + + + + + + + + + + + + + + + + + + + + Auditory + + + +
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.
Changes in Acetylcholine concentration following oral administration of Mahalaxmivilas ras with gold mahayograj guggulu with gold & Mahayograj guggulu with silver & makardhwaj Factors Initial Acetylcholine Concentration (n mol/g) Frontal Cortex After 14 days After 28 days Initial Hippocampus After 14 days After 28 days Normal Control 24.82 ±1.32 23.42 ±1.02 24.32 ±2.10 28.82 ±1.96 27.42 ±1.42 28.62 ±2.05 Mahalaxmi vilas Ras (Swarna yukta) 10 mg/ Kg body wt. -- 21.62 ±1.05 22.32 ±1.60 -- 26.45 ±2.11 25.72 ±1.82 Mahayograj Guggulu with gold 50 mg/ Kg body wt. -- 19.75 ±2.01 18.62 ±1.62 -- 23.65 ±2.75 22.60 ±2.13 Mahayograj Guggulu with Silver & Makardhwaj 50 mg/ Kg body wt. -- 18.65 ±1.82 17.52 ±1.61 -- 20.74 ±1.20 19.75 ±3.95
Changes in nor-adrenaline following oral administration of Mahalaxmivilas ras with gold mahayograj guggulu with gold & Mahayograj guggulu with silver & makardhwaj Factors Initial Frontal Cortex After 14 days Nor-adrenaline (µg/gm tissue) After 28 days Initial Hippocampus After 14 days After 28 days Normal Control 0.375 ±0.042 0.372 ±0.059 0.386 ±0.062 0.671 ±0.025 0.689 ±0.043 0.649 ±0.030 Mahalaxmi vilas Ras (Swarna yukta) 10 mg/ Kg body wt. -- 0.352 ±0.50 0.342 ±0.040 -- 0.269 ±0.052 0.631 ±0.061 Mahayograj Guggulu with gold 50 mg/ Kg body wt. -- 0.262 ±0.035 0.271 ±0.041 -- 0.520 ±0.062 0.525 ±0.025 Mahayograj Guggulu with Silver & Makardhwaj 50 mg/ Kg body wt. -- 0.240 ±0.071 0.235 ±0.062 -- 0.425 ±0.025 0.420 ±0.021
Changes in Dopamine following oral administration of Mahalaxmivilas ras with gold mahayograj guggulu with gold & Mahayograj guggulu with silver & makardhwaj Factors Initial Frontal Cortex After 14 days Dopamine (µg/gm tissue) After 28 days Initial Hippocampus After 14 days After 28 days Normal Control 0.860 ±0.025 0.872 ±0.035 0.905 ±0.065 1.245 ±0.120 1.265 ±0.112 1.282 ±0.102 Mahalaxmi vilas Ras (Swarna yukta) 10 mg/ Kg body wt. -- 0.832 ±0.040 0.845 ±0.056 -- 1.235 ±0.072 1.230 ±0.062 Mahayograj Guggulu with gold 50 mg/ Kg body wt. -- 0.725 ±0.062 0.715 ±0.032 -- 1.025 ±0.095 1.023 ±0.102 Mahayograj Guggulu with Silver & Makardhwaj 50 mg/ Kg body wt. -- 0.645 ±0.060 0.630 ±0.042 -- 0.985 ±0.072 0.980 ±0.081
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.
Toxicity studies of the subjects Evaluation of Mahayograj guggulu (with silver & Makardhwaj) on Hemopoetic system among rheumatoid arthritis cases. Factors Initial Observations After 1 month After 3 months RBC (millions/cu mm) 3.38 ±0.52 3.65 ±0.62 3.40 ±0.78 WBC (Thousand/cu mm) Polymorph (%) Lymphocytes (%) Eosinophils (%) Monocyte (%) Hb (%) 7.42 ±0.98 64.38 ±3.85 29.46 ±5.42 4.92 ±1.72 0.95 ±0.42 11.05 ±2.35 6.85 ±1.12 65.72 ±4.01 28.78 ±4.03 5.42 ±1.65 0.86 ±0.48 10.80 ±2.15 7.38 ±1.02 63.01 ±3.48 27.32 ±5.62 3.82 ±1.35 0.92 ±0.45 11.35 ±2.32
Evaluation of Mahayograj guggulu (with silver & Makardhwaj) on Liver function tests among rheumatoid arthritis cases. Factors Alkaline phosphates (kings Au/100ml) GGTP (IU) SGOT (IU) SGPT (IU) Serum Billirubin (mg%) Total Protein (gm%) Initial 8.82 ±2.75 29.01 ±4.34 48.85 ±4.98 38.83 ±3.25 0.85 ±0.25 5.20 ±1.10 Observations After 1 month 10.13 ±3.08 28.64 ±3.40 49.75 ±3.02 40.63 ±3.01 0.96 ±0.16 4.60 ±1.70 After 3 months 9.18 ±1.75 26.62 ±5.01 46.62 ±5.20 44.01 ±3.98 0.83 ±0.20 5.65 ±1.85
Evaluation of Mahayograj guggulu (with silver & makardhwaj) on Renal function tests among rheumatoid arthritis cases. Factors Blood Urea (mg%) Serum Creatinine (mg%) Serum Sodium (meq( meq/l) Serum Potassium (meq/l) Creatinine clearance (ml/min) Initial 25.72 ±3.01 0.72 ±0.21 139.65 ±12.62 3.86 ±0.98 117.82 ±11.64 Observations After 1 month 27.25 ±3.42 0.80 ±0.11 132.82 ±15.01 4.50 ±0.81 121.65 ±12.95 After 3 months 23.28 ±4.96 0.75 ±0.13 137.62 ±16.92 3.96 ±0.78 118.86 ±13.76 122 121 120 ml/minute 119 118 Creatinine clearance 117 116 115 Initial After 1 months After 3 months
Level of lead in blood and urine following oral administration of Mahayograj guggulu (with silver & makardhwaj) in rheumatoid arthritis cases 80 70 60 µg/dl 50 40 30 Blood Urine 20 10 0 Initial After 1 month After 2 months After 3 months Normal range In Blood <29 µgm/dl In Urine < 2.3 µgm/dl
Level of mercury in blood and urine following oral administration of Mahayograj guggulu (with silver & makardhwaj) in rheumatoid arthritis cases 25 20 µg/dl 15 10 Blood Urine 5 0 Initial After 1 month After 2 months After 3 months Normal range In Blood < 2.0 µgm/dl In Urine < 2.3 µgm/dl
Level of Arsenic in blood and urine following oral administration of Mahayograj guggulu (with silver & makardhwaj) in rheumatoid arthritis cases µg/dl 18 16 14 12 10 8 6 4 2 0 Initial After 1 month After 2 months After 3 months Blood Urine Normal range In Blood < 3.0 µgm/dl In Urine < 8.4 µgm/dl
Elimination of lead after withdrawal 60 of Mahayograj guggulu with silver and makardhwaj :-: µgm/dl 40 20 0 Urine Blood Initial After 7 days After 15 days
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.