Transcript Dr. GP Dubey

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



i.
Promotive
Preventive
Curative
Non-Pharmacologic
procedures:
Diet,
exercise,
yogic-meditation
relaxation
practices, observance of sadvritta (sociocultural conduct) as per doshik setup, and
circadian and seasonal variation.
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:

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.
Physico-chemical characterization
Distribution, Bio-transformation and Elimination
Route of Absorption
:
Inhalation of Vapor, subcutaneous 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
WHO Limit
Normal permissible concentration
Heavy Metals
Mercury
Arsenic
Lead
Blood
0.2-3 ng/ml
1.1 µgm/Lit.
0.02-1.0 µgm/Lit.
Copper
Aluminium
Nickel
100-200 µgm/dl
1-10 ng/ml
0.05-1 ng/ml
Magnisium
1.8-3 mg/dl
Zinc
Iron
50-150 µgm/Lit.
50.175 µgm/Lit.
Normal and obtained level of elements in
blood and urine
Blood (µg/dl)
Element
s
Normal
Value
Urine (µg/dl)
Obtained Value
Urban
Rural
Normal
Value
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
150
6
6
0/6
0/6
200
250
300
6
6
6
0/6
0/6
0/6
No lethality was found at the highest dose of
300mg/kg/day
Neurobehavioral toxicity following Makardhwaj
(Dose 50 mg/kg)
Observations
Tests
Initial
After 6
hrs
After 12
hrs
After 24
hrs
Flexing
reflex
+
+
+
+
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, Gastrointestinal, Hepatic & kidney function test
were noticed.
Normal Micro angiography of the Kidney
Right Kidney
Left Kidney
Dose 2.5 mg/kg body wt
Damage with
HgCl2 (Low Dose)
Dose 5.0 mg/kg body wt
Damage with HgCl2
(High Dose)
HgCl2 2.5 mg/kg body wt;
Makardhwaj 12.50 mg/kg body wt
Makardhwaj +HgCl2
Effect of Makardhwaj on serotonin level in
experimental rats
Treated
Group
No.
of
animal
Serotonin (µ gm/gm tissue)
Frontal Cortex
Hippocampus
7 days
14 days
7 days
14 days
Normal
control
(ACSF 5ml)*
10
0.422
± 0.088
0.418
± 0.075
0.362
± 0.092
0.364
± 0.084
Makardhwaj
300 mg/kg
**
10
0.316
±0.061
0.364
±0.054
0.241
±0.042
0.201
±0.064
Makardhwaj
100 mg/kg
***
10
0.438
±0.082
0.456
±0.072
0.384
±0.065
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
nor-adrenaline(µ gm/gm tissue)
Treated
Group
No. of
animal
Normal control
(ACSF 5ml)*
10
Makardhwaj
300 mg/kg
**
10
Makardhwaj
100 mg/kg
***
10
Total brain
Mid brain
7 days
14 days
7 days
14 days
0.368
±0.067
0.376
± 0.058
0.621
± 0.092
0.631
± 0.085
0.222
0.216
0.408
0.402
±0.045
±0.051
±0.039
±0.061
0.384
0.388
0.642
0.650
±0.085
±0.078
±0.098
±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
No. of
animal
Normal control
(ACSF 5ml)*
Total brain
Mid brain
7 days
14 days
7 days
14 days
10
0.836
±0.082
0.842
±0.074
1.272
±0.092
1.208
±0.088
Makardhwaj
300 mg/kg
**
10
0.664
±0.050
0.641
±0.033
1.156
±0.024
1.108
±0.052
Makardhwaj
100 mg/kg
***
10
0.841
±0.101
0.858
±0.104
1.289
±0.088
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
in experimental rats
ChAT activity (n mol/mg protein/hour)
Treated
Group
No. of
animal
Normal control
(ACSF 5ml)*
Frontal cortex
Hippocampus
7 days
14 days
7 days
14 days
10
22.34
±2.85
23.97
±3.11
20.24
±2.12
19.88
±2.75
Makardhwaj
300 mg/kg
**
10
18.21
±2.01
16.14
±2.11
16.22
±3.01
14.06
±3.10
Makardhwaj
100 mg/kg
***
10
24.14
±3.02
25.68
±2.94
21.98
±3.94
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
Flakes
particles
Fused &
Fine
Spherical
Solidification
particles
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
Observations
Initial
After 24 hrs. After 48 hrs. After 72 hrs.
Flexing
reflex
+
+
+
+
Grasping
reflex
+
+
+
+
Corneal
reflex
+
+
+
+
Body
equilibrium
+
+
+
+
Head
shaking
+
+
+
+
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 Gastrointestinal, 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
Normal Control
Acetylcholine Concentration (n mol/g)
Frontal Cortex
Hippocampus
After 14
After 28
After 14
Initial
days
days
days
After 28
days
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
Normal Control
Nor-adrenaline (µg/gm tissue)
Frontal Cortex
Hippocampus
After 14
After 28
After 14
Initial
days
days
days
After 28
days
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
Normal Control
Dopamine (µg/gm tissue)
Frontal Cortex
Hippocampus
After 14
After 28
After 14
Initial
days
days
days
After 28
days
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
Observations
Initial
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)
7.42
±0.98
6.85
±1.12
7.38
±1.02
64.38
±3.85
29.46
±5.42
4.92
±1.72
0.95
±0.42
11.05
±2.35
65.72
±4.01
28.78
±4.03
5.42
±1.65
0.86
±0.48
10.80
±2.15
63.01
±3.48
27.32
±5.62
3.82
±1.35
0.92
±0.45
11.35
±2.32
Polymorph (%)
Lymphocytes (%)
Eosinophils (%)
Monocyte (%)
Hb (%)
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%)
Observations
Initial
After 1 month
After 3 months
8.82
±2.75
10.13
±3.08
9.18
±1.75
29.01
±4.34
48.85
±4.98
38.83
±3.25
0.85
28.64
±3.40
49.75
±3.02
40.63
±3.01
0.96
26.62
±5.01
46.62
±5.20
44.01
±3.98
0.83
±0.25
±0.16
±0.20
5.20
4.60
5.65
±1.10
±1.70
±1.85
Evaluation of Mahayograj guggulu (with silver
& makardhwaj) on Renal function tests among
rheumatoid arthritis cases.
Observations
Factors
Initial
Blood Urea (mg%)
Serum Creatinine
(mg%)
Serum Sodium (mEq/L)
Serum Potassium
(mEq/L)
Creatinine clearance
(ml/min)
25.72
±3.01
0.72
±0.21
139.65
±12.62
3.86
±0.98
117.82
±11.64
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
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
g/dl
50
Blood
Urine
40
30
20
10
0
Initial
After 1 month
After 2 months
After 3 months
Normal range – In Blood <29 gm/dl
In Urine < 2.3 gm/dl
Level of mercury in blood and urine following oral
administration of Mahayograj guggulu (with silver
& makardhwaj) in rheumatoid arthritis cases
25
g/dl
20
15
Blood
Urine
10
5
0
Initial
After 1 month
After 2 months
After 3 months
Normal range – In Blood < 2.0 gm/dl
In Urine < 2.3 gm/dl
Level of Arsenic in blood and urine following oral
administration of Mahayograj guggulu (with silver
& makardhwaj) in rheumatoid arthritis cases
18
16
g/dl
14
12
10
Blood
Urine
8
6
4
2
0
Initial
After 1 month
After 2 months
After 3 months
Normal range – In Blood < 3.0 gm/dl
In Urine < 8.4 gm/dl
Elimination of lead after withdrawal
of Mahayograj guggulu
with silver and makardhwaj :-
gm/dl
60
40
Urine
Blood
20
0
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.