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Indian Journal of Experimental Biology

Vol. 38, May 2000, pp. 409-414

Mini Review

Molecular approach to Ayurveda


Yarnini B Tripathi
Department of Medicinal Chemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India

In ayurvedic system of medicine, it is considered that a living system is made of panch-mahabuta, in the form of Vata,
piua and kapha at the physical level and satwa, raja and tama at the mental level. This covers the psychosomatic
constitution and commonly known as the Tridosh theory. The imbalance in these body humours is the basic cause of any
type of disease manifestation. Till date, several objective parameters have been proposed to monitor the level of these basic
humours but none of them is complete. In this exercise, now it is proposed to consider free radical theory of diseases as one
of the objective parameters. To be more specific, vata can be monitored in terms of membrane bound signal transduction,
pilla as the process of phosphorylation and de-phosphorylation of different proteins (signalling moieties and enzymes) and
kapha can be viewed as the degree of gene expression as protein synthesis. This can be correlated with the ojas of the body
or total body defence mechanism.

Till date the scientists are struggling hard to explain Pittam pangu Kappah pangu, pangaq maladh atvah
the basic concepts of the Ayurveda in scientific v ayun yatra niyante, tatra gachanti meghavatq
1
terms . The Tridosh theory of Vata, Pitta and Kapha, (Shamgadhar Purva, 5.25)
concept of Ama and Agni, the holistic approach of
2
disease management, are some of them . Ayurveda, (As the wind carries the clouds in the sky, similarly
not only describes the use of herbal medicine for the Vata carries the pitta and kapha, in the body).
management of different diseases, but it also The increase in Vata is due to the intake of
emphasizes the way of life. The objective of unwholesome diet, excessive exercise, excess stress,
Ayurveda is to maintain the health of a healthy person poor nutrition and ageing, In the metabolic diseases
and to cure the disease of a patient. Regarding like diabetes, arthritis, ageing, Alzheimer's disease,
treatment aspect, this system indicates t)Jat 66% of loss of memory, atherosclerosis etc also, Vata is said
the diseases could be managed only by changing diet, to be increased above the normal level. This leads to
13
life style and environmental factors . Under the the accumulation of vitiated pitta, kapha and Ama ·
holistic approach of Ayurveda, the individual and its as indicated in the original ayurvedic text, given
surrounding environment is considered as a single below.
unit for the diagnosis and treatment. Basically in the
Ayurvedic system of medicine, the basis of life is R u ksais tiktaih kas a yaih katubhirasanair
based . on three body humours i.e. Vata, Pitta and vegasandh a ranaisca. Vy a y amaissca vyavaih
Kapha at the body level and Satva, Raja and Tama, at prataranabalavad vigrair j a garais ca.
the mental leve l. Further it is said that the human Sy am a nivarakanguprabhritibhir as a nair
body consists of 7 different tissues i.e. Rasa (body ull a sadbhih payodaih. -anne jirne 'pi jantor iti
fluids), RAKTA (blood), Mansa (muscle), Ma zza bhabati tanau m a ritasya prakopah.
111
(bone marrow), Meda (fat), Asthi (bone) and Shukra Tisasta 's Cikits a kalik a, +654 29. (I 0 chapter)
(sperm); 13 srotasa (functional systems) and 13
agnies (enzyme systems). Vata is the most important (Provocation of Vata takes place by intake of
humour, as it carriers the Pitta and Kapha in the body rough, bitter, astringent and pungents, fasting,
to their respective places, for their normal functions. suppression of urges , exertion, sexual act, swimming,
In other words, Vata is the indication of life and fighting with stranger, vigils, intake of rough cereals
without this, a living system is dead. It has been like, syamaka, nivara, a kangu etc. in cloudy weather
clearly mentioned in the following Sanskrit shlokas of (early rainy season), and after digestion of food (on
ancient Ayurvedic text. empty stomach.).
410 INDIAN J EXP BIOL, MAY 2000

The etiological factors, responsible for different and curry, excessive exercise, mental stress 8 etc. In
diseases. and their development has been described in modem medicine their management includes, anti
detail in the Ayurvedic system of medicine. Here oxidants (both natural and synthetic) 9• 11 and metal
health has been classified in two forms, a) physical chelators 6 .
and b) psychic. It emphasize, the 4 basic causes for
These free radicals undergo a chain reaction of
the onset of different diseases (I) ·genetic (2)
attacking double bonds of different macromolecules
psychosomatic (3) environmental factors and (4) the
leading to the production of irreversible chemical
abnormal activity of sensory organs.
modifications in them. Some of the end products of
For the management of those factors which involve
this process get eliminated from the body by the
the imbalance of Vata diseases, a particular way of
action of cellular proteases but some of them become
life (code of conduct) and a special group of
unfit for the natural constitutive proteases and
medicines are recommended, which are called as
lysozomal enzymes and therefore get accumulated,
Rasayana drugs. The actual meaning of Rasayana is
because of their inability to enter to the normal
to follow those things which prevent ageing and
metabolic pathway or elimination.
keeps an individual healthy. It includes the medicine,
the diet and also the life style. Interestingly, Similar to the above analogy, Ayurvedic system of
aggravated vata could be checked by taking special medicine considers a term, Ama which is the vitiated
diet, stress-free life, holy thoughts etc. and this rasa (transformed end product of food due to
approach of treatment (changed life style and use of abnormal activity of agni) . Ama is produced and
rasayana) not only cures the diseases but also keeps a accumulated due to the abnormal level of the 3 body
man healthy with long life as described below: humours i.e. vata, pitta and kapha and 3 mental
humours i.e. sata, raja and tama 12• The concept of
Dh a rghm a yus smri tim medh a marogyam tarunam Ama, as described earlier, has a great similarity with
vayah the end products of free radical reactions. The
prabh.a varna svaru daryam dehendriyabala m accumulation of "Ama" could be compared with the
param accumulation of lipofusin, amyloid bodies 1', modified
La bhopayohi sa sta na m rasa dana m proteins and lipids (which are not suitable for further
rasa yanam. metabolism by the normal cellular pathways). This
(Charak Samhita Ch .Str Chap-11117-8) process is the outcome of the deviation of different
metabolites from the main metabolic pathway to such
14
a direction, which forms the defective end products •
(It prolongs the life span, increases memory and
retaining capacity together with maintaining the The concept of agni is another important issue in
general health. It keeps the person young with bright the Ayurvedic literature. They are of 13 types.
complexion, sweet voice, strong body and sensitive Among them there is one Jatharagni, 5 Bhutagni and
3
sense organs. Rasayana therapy is also meant to 7 types of Dhatwaganis . Agni is considered as the
achieve the goal s of life and to maintain the optimum uniting factor for body and mind . One agni may be
quality of all the seven dhatus (body constituents) as considered as a set of enzymes, responsible for a
described earlier. particular metabolic pathway. Their site of action is
Interestingly, this concept of Ayurveda resembles also different and very specific e.g. Jatharagani acts
with the free radical theory of diseases and ageing. As on the Gastrointestinal tract, Bhutagni acts on the
it is known that along with the evolution of living intermediary metabolism and Dharn:agni acts at the
organisms, the involvement of oxygen and iron in the cellular level. The activity of Jatharagani is directly
4
life process became more significant . Now it is well related to the activity of other 12 agnies, therefore it
established that at one hand, these molecules are is considered to be the most important among all. As
essential for any aerobic organism but at the same per classical ayurvedic texts, any disease
time they are highly toxic also, when produced in manifestation is mediated through the abnormal
excess 5 . The different causes of excess generation of functioning of agni. The medicines for maintaining
free radicals are the excess activity of electron the optimum activity of the agni (enzymes) will
transport chain (ETC), excess of free iron in the maintain the formation of proper dhatus and do not
bodl, hyperoxia 7, pollution, radiation, hurry, worry allow the formation and accumulation of Ama. This is
TRIPATHI : MOLECULAR APPROACH TO AYURYEDA 411

another evidence for the holistic approach of or free radical mediated . Out of them more than 56
Ayurveda for health management. diseases have been included in the list of free radical
16
On the contrary, the hyper-activity of the mediated diseases • To make it clear, we consider the
Dhatwagni (metabolic enzymes), aggravates vata example of two vatic diseases, now known as free
17
followed by the activation of pitta and ultimately the radical mediated i.e. atherosclerosis and
18
vitiation of kapha, and the accumulation of Ama. Thi s Alzheimer's disease • As per recent scientific
process finall y manifests the symptoms of different reports, they are inflammation bound diseases and the
vata di seases (Fig. I ) . For the removal of different same set of genes are responsible for both the
types of ama, different Agnies have to be activated, diseases. Although, the affected organs are different
either by medic ine or by change in habits, and the symptoms are different, but the causes are
environmental factors or life style. As per modern similar at the molecular level. This hypothes is is
theory, the structural changes in the enzymes at the similar to what has been told by the Ayurveda experts
level of transcription or translation , produce defective in the name of Vata disturbance for several such
enzymes lead in g to the production of altered- metabolic diseases.
intermediary metabo lite or accumulation or excess Coming to the specific di sease, Ayurveda covers
use of some of the intermediary metabolite 15 • atherosclerosis as a complication of Medo raga
19
However, till date, we have not been able to give a (obesity). According to Sushruta , such disorders
similar classification of different enzyme sys tems or occur due to the coverage of margs (channels or
biochemical pathways, as given for agni, but future Srotas) by meda dhatu (by the accumulation of lipids)
studies will tell the truth . Thi s is just the beginning of resulting to the hypo-activity of Dhatwagnies
the story. (disturbed signaling pathway). Due to imbalance of
Another similarity between the basic concepts of agni at the dhatu level (Dhatwagnia), the rasa of
Ayurveda and free radical theory is the classification ingested food , (partially digested food or the
of vatic diseases and free radical mediated di seases. intermediary metabolite) is not properly converted to
12 different types of Dhatus (ti ssues) because of
Vatic diseases are of 80 types . Interestingly they
include all those diseases, which are either metabolic incomplete assimilation and leads to excess
deposition of meda dhatu (fat ti ssue) along with the
Environment and constitution simultaneous depletion of other dhatus. Thi s leads to
different complications of medo raga including
atherosclerosis 20 . (Fig.2)
As per recent scientific information, there are
basically three mechanisms, involved in
atherosclerosis. These are lipid infiltration, cellular
Pitta & Kapha 21
invasion and cell proliferation which is similar to
Meda deposition and coverage of channels as
described above. One of the hypotheses is the
involvement of free radical s and nitric oxide (high
Disturbance in Agni Vata), which may be due to the high concentration of
(Jath aragani , + Dhatwagani)
advanced glycosylation end products22 (Ama).

+
Disturbance in the metabolism Rasa and
Secondly, the oxidized LDL in the blood stimul ates
the monocyte binding and the production of
chemotactic factors (high pitta or high enzyme
activity) for the adhesion of monocytes to the

+
Production of ama
endothelial cells22 .
Similarly, when we talk about the life sty le and

~
diet , then at biochemical level: (A) hurry could be
correlated with the high acti vity of mitochondri a,
Manifestation of disease symptoms producing high amount of superoxides as the by
product of electron tran sport chain, (B) worry is
Fig. I -Concept of Ayurveda for the development of a disease related to high releases of catecholamine, which on
412 INDIAN J EXP BIOL, MAY 2000

Ahar

~
Digestion and Jatharagani
Absorption

Excess synthesis
of Lipid (Meda)
Meda/Sneha
Low Medagni

l
EJ
Fig. 2-Etiology of atherosclerosis (Ayurvedic view)

reaction with the free iron in the body, produces more VATA PITTA KAPHA
hydroxyl radical s and, (C) curry indicates excess
Wind Bile P legm
intake of fat , which is the best su bstrate for lipid
peroxidation, because of more unsaturated bonds. The Nervous system Thermogenesis Thermotaxis and
mechanism underlies the modul ation of various formation of
signaling molecules leading to the activation of preservatives fluid
NFkB, which regulates the expression of genes,
Hormones Enzymes Immune system
responsibl e for inflammatory factors and chemotactic
agents such as Vascular cell adhesion molecule-1 , Membrane bound Phosphoryl- Gene expression
(VCAM-1 ), endothelial leukocyte adhesion signal transduction ation processes
molecule, (ELAM-1) E-selectin, Intercellular
23 Stimulus-receptor, Metabolic steps Defence system
adhesion mol ecu le- 1, ICAM-1 etc. (These can be
interaction
compared to high kapha as hyptothesis) .
For Alzheimer's di sease, there are 3 poss ible Fig. 3-Proposed hypothesis for developing th e subjective
causes e.g. free radical theory , amyloid body parameters to monitor three body humours, desc ribed in Ayurv
2 4
deposition and Ca + toxicit/ . At the molecular level ,
there is activation of NFkB, which enhances the accumulation of Ama in the brain and nervou s tissue.
express ion of cyclooxygenase-2 and ultimately the It leads to the inflammation and degeneration of the
24
induction of infl ammat ion in the brain ti ssue . Beta cells. It is a general principle for the development of
amyloid bodies are the tran sformed proteins, Vataj di seases where it is said that the disturbed Vata
12
produced as the outcome of the defec tive APP affects the agni and then produces ama .
(A ltered precursor protein)u. Their excess For the management of such diseases, Ayurveda
accumulation, degenerates the neural cells. Another describes the use of Rasayana drugs . In this system of
factor is th e excess of Ca 2+ in the cytoplasm, which is medicine, special attention has been paid to thi s
the outcome of hyperactivity of the glutamate branch, as it is anti ageing. It not only recommends
receptor and al so the calcium channels on the cell for the use of herbal medicine but also includes the
membrane. This hi gh cellular calcium triggers the code of conduct and life style. Interestin gly a range of
production of free radicals, and the process of lipid herbs have been described for different age groups as
18
peroxidation and finally neuron damage • Ayurveda rasayan therapy. It opens the channels of the body and
believes, that mental disorders are the basic cause for leads to the normal metabolism of ingested food . It
the tncrease tn Vata (Prana/Vata) and the brings vitality to all the Dhatus (body syste ms and
TRIPATHI : MOLECULAR APPROACH TO AYURV EDA 413

their organs). It is further recommended for the 2 Charak Samhit- chikitsa sutra-57 .
regular intake of these medicines after the age of 25- 3 Tripathi S N & Tripathi Y B, Medical systems with a holistic
approach, (S NTMF Publi shers, Varanasi, India) 1993.
30, as the diet supplement to prevent the ageing
2 4 Me Cord J M & Fridovich I. The biology and pathology of
process \ which is considered as a vata mediated oxygen radicals. Ann Internal Med, 89 ( 1978), 122.
disease in the ayurvedic texts . 5 Braughlen J M, Duncan LA & ChaseR L. The involvement
of iron in lipid peroxidati on. 1 Bioi Chem, 264 ( 1996) I0282 .
Rasayanam Cha Yattjjara Vyadhi Naashanam
6 Braughlen J M, ChaseR L & Pregenzen J F. Stimulation and
Yatha Amrita Rudanti Cha Gugguluchah Haritaki inhibition of iron dependent Lipid peroxidation by
25
(Rasayana prevents ageing process) desferoxamine. Biochem Biophys Res Commun, 153 ( 1988)
933 .
On the similar pattern , now a days, the use of
7 Groot H & Noll T. The role of physiological oxygen parial
antioxidants has come to practice. It is both pressure in lipid peroxidation. Theoretical consideration and
preventive as well as curative. Specifically the experimental evidence. Chem Phys Lipids, 44 ( 1987) 209.
medicines, responsible for the management of free 8 Emerit I & Chance B (Eds) in Free radicals and ageing,
radical medi ated di seases are called antioxidants26 . (Birkhauser Verl ag Basel, Swetzerland) 1992.
9 Lippman R D, Free radicals induced lipid peroxidation and
They inactivate the reacti ve free radicals, which are
aging in Hand book of free radicals and anti oxidants in
spontaneously being produced in the normal biomedicine, edited by Miquel J, Quintanillia AT and Weber
physiologica l processes, spec ially in the electron H (CRC Press), 1980.
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antioxidant enzymes at the molecular level, these II Di Mascio P & Murphy M E. Antioxidant defence systems :
the role of carotenoids tocopherols and thiols. Am 1 C/in
antioxidants attenuate the activation of NFkB and Nutr, 53 ( 199 1) 1945 .
several other tran scription factors, leading to the 12 Charak Samhita: Chapter 28, vata chikitsa.
27
regulation of gene expression , activity of ion 13 Sinha S & Lieberburg I. Normal metabolism of the amyloid
channels and different enzymes, speci ally the kinases, precursor protein (APP). Ne urodegeneration, I ( 1992) 169.
which are important in the signaling cascade28 . 14 Stahl Stephen M, (ed) Cogn itive enhancers and
neuroprotective agents, in Essential psychopharmacology
Interestin gly, several herbal medicines including
(Cambridge University Press) 1996,289.
many Rasayana drugs have shown the antioxidant 15 Kemeny M E, Cohen F, Zegans L S & Conant M A
property as indi cated by several scienti sts but we are Psychosom Med, 51 ( 1989) 195.
quoting some of the reports from our own 16 Harman D. The ageing process: Major risk factors for
9 37 diseases and death. ?roc Not / A cad Sci USA , 88: ( 1991 ),
laborator/ - fo r ready reference. Like rasayana
5360-63.
drugs , the anti ox idants are also reco mmended as the
17 Ross R. The pathogenesi s of atherosclerosis: A perspecti ve
diet supplement , to be taken in early age as a for the 1990' s. Na ture, 3262 ( 1993): 80 1-808.
preventive measure for different old age di seases. It 18 Copper, J Bl oom, PE & Roth R H, Th e biochemical basis of
also acts as the signaling mo lecule by itself. In thi s neuropharmacology, 7'h editi on Univ Press Oxford , (New
way, it appears that most of the properties of free York), 1996.
radicals are simil ar to th at of Vata as desc ribed in 19 Sushruta Samhita, Sutra 15/37 .
20 Tripathi S N Clinical & ex perimental tri al of guggulu
Ayurveda. Th erefore, a hypothesis could be made th at
(Monograp h) in Medoroga (lipid di sorders) (Department of
the free radi cals and re lated anti oxidant enzy mes and Kayac hikitsa, IMS , BHU, Varanasi, India) 1975.
molecul es could be treated as one of the objective 2 1 Fuster Valentin (Ed) Syndromes of atherosclerosis,
parameters for the assessment of vata and ojas. Monograph Series of American Heart Association (Futura
Similarly, the other terms of Ayurveda could also be Publishing Co, Inc Armonk, New York) 1996.
22 Steingiberg D. Antioxidants and atherosclerosis: A curren t
defin ed as some objec ti ve parameters, as given in
perspective, Circulation, 86 ( 199 1): 1420.
Fig. 3. 23 Tripathi B, Rajavashi sth , Andalibi A, Territo M C, Berliner J
A, Navab M , Fogelman A M, & Lu sis A J. Induction of
Acknowledgement
endothalial cell expression of granulocyte and mac rophage
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and Prof G .P .Dubey for di scuss ion on the subject. 24 Lukis W 1 & Bazan N G. Strong Nuclear Factor kB - DNA
binding parallels cyclooxyagenase-2 gene transcripti on in
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