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 the basic concepts of the Ayurveda in scientific terms 1

. The Tridosh theory of Vata, Pitta and Kapha, concept of Ama and Agni, the holistic approach of disease management, are some of them 2

. Ayurveda, not only describes the use of herbal medicine for the management of different diseases, but it also emphasizes the way of life. The objective of Ayurveda is to maintain the health of a healthy person and to cure the disease of a patient. Regarding treatment aspect, this system indicates t)Jat 66% of the diseases could be managed only by changing diet, life style and environmental factors . Under the holistic approach of Ayurveda, the individual and its surrounding environment is considered as a single unit for the diagnosis and treatment. Basically in the Ayurvedic system of medicine, the basis of life is based . on three body humours i.e. Vata, Pitta and Kapha at the body level and Satva, Raja and Tama, at the mental level. Further it is said that the human body consists of 7 different tissues i.e. Rasa (body fluids), RAKTA (blood), Mansa (muscle), Mazza (bone marrow), Meda (fat), Asthi (bone) and Shukra (sperm); 13 srotasa (functional systems) and 13 agnies (enzyme systems). Vata is the most important humour, as it carriers the Pitta and Kapha in the body to their respective places, for their normal functions. In other words, Vata is the indication of life and without this, a living system is dead. It has been clearly mentioned in the following Sanskrit shlokas of ancient Ayurvedic text.

Pittam pangu Kappah pangu, pangaq maladh a tvah v a yun yatra niyante, tatra gachanti meghavatq (Shamgadhar Purva, 5.25)

(As the wind carries the clouds in the sky, similarly Vata carries the pitta and kapha, in the body).

The increase in Vata is due to the intake of unwholesome diet, excessive exercise, excess stress, poor nutrition and ageing, In the metabolic diseases like diabetes, arthritis, ageing, Alzheimer's disease, loss of memory, atherosclerosis etc also, Vata is said to be increased above the normal level. This leads to the accumulation of vitiated pitta, kapha and Ama 1

·3

as indicated in the original ayurvedic text, given below.

R u ksais tiktaih kas a yaih katubhirasanair vegasandh a ranaisca. Vy a y a maissca vyavaih prataranabalavad vigrair j a garais ca. Sy am a nivarakanguprabhritibhir as a nair ull a sadbhih payodaih. -anne jirne 'pi jantor iti bhabati tanau m a ritasya prakopah. Tisasta 's Cikits a kalik a, +654 29. (I 0111 chapter)

(Provocation of Vata takes place by intake of rough, bitter, astringent and pungents, fasting, suppression of urges , exertion, sexual act, swimming, fighting with stranger, vigils, intake of rough cereals like, syamaka, nivara, a kangu etc. in cloudy weather (early rainy season), and after digestion of food (on empty stomach.).

410 INDIAN J EXP BIOL, MAY 2000

The etiological factors, responsible for different diseases. and their development has been described in detail in the Ayurvedic system of medicine. Here health has been classified in two forms, a) physical and b) psychic. It emphasize, the 4 basic causes for the onset of different diseases (I) ·genetic (2) psychosomatic (3) environmental factors and (4) the abnormal activity of sensory organs.

For the management of those factors which involve the imbalance of Vata diseases, a particular way of life (code of conduct) and a special group of medicines are recommended, which are called as Rasayana drugs. The actual meaning of Rasayana is to follow those things which prevent ageing and keeps an individual healthy. It includes the medicine, the diet and also the life style. Interestingly, aggravated vata could be checked by taking special diet, stress-free life, holy thoughts etc. and this approach of treatment (changed life style and use of rasayana) not only cures the diseases but also keeps a man healthy with long life as described below:

Dh a rghm a yus smri tim medh a marogyam tarunam vayah prabh. a varna svaru daryam dehendriyabala m param La bhopayohi sa sta na m rasa dana m rasa yanam. (Charak Samhita Ch.Str Chap-11117-8)

(It prolongs the life span, increases memory and retaining capacity together with maintaining the general health. It keeps the person young with bright complexion, sweet voice, strong body and sensitive sense organs. Rasayana therapy is also meant to achieve the goal s of life and to maintain the optimum quality of all the seven dhatus (body constituents) as described earlier.

Interestingly, this concept of Ayurveda resembles with the free radical theory of diseases and ageing. As it is known that along with the evolution of living organisms, the involvement of oxygen and iron in the life process became more significant4

. Now it is well established that at one hand, these molecules are essential for any aerobic organism but at the same time they are highly toxic also, when produced in excess5

. The different causes of excess generation of free radicals are the excess activity of electron transport chain (ETC), excess of free iron in the bodl, hyperoxia 7

, pollution, radiation, hurry, worry

and curry, excessive exercise, mental stress8 etc. In modem medicine their management includes, anti oxidants (both natural and synthetic)9

•11 and metal

chelators6.

These free radicals undergo a chain reaction of attacking double bonds of different macromolecules leading to the production of irreversible chemical modifications in them. Some of the end products of this process get eliminated from the body by the action of cellular proteases but some of them become unfit for the natural constitutive proteases and lysozomal enzymes and therefore get accumulated, because of their inability to enter to the normal metabolic pathway or elimination.

Similar to the above analogy, Ayurvedic system of medicine considers a term, Ama which is the vitiated rasa (transformed end product of food due to abnormal activity of agni) . Ama is produced and accumulated due to the abnormal level of the 3 body humours i.e. vata, pitta and kapha and 3 mental humours i.e. sata, raja and tama 12

• The concept of Ama, as described earlier, has a great similarity with the end products of free radical reactions. The accumulation of "Ama" could be compared with the accumulation of lipofusin, amyloid bodies 1

', modified proteins and lipids (which are not suitable for further metabolism by the normal cellular pathways). This process is the outcome of the deviation of different metabolites from the main metabolic pathway to such a direction, which forms the defective end products 14

•

The concept of agni is another important issue in the Ayurvedic literature. They are of 13 types. Among them there is one Jatharagni, 5 Bhutagni and 7 types of Dhatwaganis3

. Agni is considered as the uniting factor for body and mind . One agni may be considered as a set of enzymes, responsible for a particular metabolic pathway. Their site of action is also different and very specific e.g. Jatharagani acts on the Gastrointestinal tract, Bhutagni acts on the intermediary metabolism and Dharn:agni acts at the cellular level. The activity of Jatharagani is directly related to the activity of other 12 agnies, therefore it is considered to be the most important among all. As per classical ayurvedic texts, any disease manifestation is mediated through the abnormal functioning of agni. The medicines for maintaining the optimum activity of the agni (enzymes) will maintain the formation of proper dhatus and do not allow the formation and accumulation of Ama. This is

TRIPATHI : MOLECULAR APPROACH TO AYURYEDA 411

another evidence for the holistic approach of Ayurveda for health management.

On the contrary, the hyper-activity of the Dhatwagni (metabolic enzymes), aggravates vata followed by the activation of pitta and ultimately the vitiation of kapha, and the accumulation of Ama. This process finall y manifests the symptoms of different vat a diseases (Fig. I ) . For the removal of different types of ama, different Agnies have to be activated, either by medic ine or by change in habits, environmental factors or life style. As per modern theory, the structural changes in the enzymes at the level of transcription or translation , produce defective enzymes lead ing to the production of altered­intermediary metabolite or accumulation or excess use of some of the intermediary metabolite 15

•

However, till date, we have not been able to give a similar classification of different enzyme sys tems or biochemical pathways, as given for agni, but future studies will tell the truth . Thi s is just the beginning of the story.

Another similarity between the basic concepts of Ayurveda and free radical theory is the classification of vatic diseases and free radical mediated diseases. Vatic diseases are of 80 types 12

. Interestingly they include all those diseases, which are either metabolic

Environment and constitution

Pitta & Kapha

Disturbance in Agni (Jatharagani , + Dhatwagani)

+ Disturbance in the metabolism Rasa and

+ Production of ama

~ Manifestation of disease symptoms

Fig. I -Concept of Ayurveda for the development of a disease

or free radical mediated . Out of them more than 56 diseases have been included in the list of free radical mediated diseases 16

• To make it clear, we consider the example of two vatic diseases, now known as free radical mediated i.e. atherosclerosis 17 and Alzheimer's disease 18

• As per recent scientific reports, they are inflammation bound diseases and the same set of genes are responsible for both the diseases. Although, the affected organs are different and the symptoms are different, but the causes are similar at the molecular level. This hypothesis is similar to what has been told by the Ayurveda experts in the name of Vata disturbance for several such metabolic diseases.

Coming to the specific di sease, Ayurveda covers atherosclerosis as a complication of Medo raga (obesity). According to Sushruta 19

, such disorders occur due to the coverage of margs (channels or Srotas) by meda dhatu (by the accumulation of lipids) resulting to the hypo-activity of Dhatwagnies (disturbed signaling pathway). Due to imbalance of agni at the dhatu level (Dhatwagnia), the rasa of ingested food , (partially digested food or the intermediary metabolite) is not properly converted to different types of Dhatus (ti ssues) because of incomplete assimilation and leads to excess deposition of meda dhatu (fat ti ssue) along with the simultaneous depletion of other dhatus. This leads to different complications of medo raga including atherosclerosis20

. (Fig.2)

As per recent scientific information, there are basically three mechanisms, involved in atherosclerosis. These are lipid infiltration, cellular invasion and cell proliferation21 which is similar to Meda deposition and coverage of channels as described above. One of the hypotheses is the involvement of free radicals and nitric oxide (high Vata), which may be due to the high concentration of advanced glycosylation end products22 (Ama). Secondly, the oxidized LDL in the blood st imulates the monocyte binding and the production of chemotactic factors (high pitta or high enzyme activity) for the adhesion of monocytes to the 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 activity of mitochondri a, producing high amount of superoxides as the by product of electron transport chain, (B) worry is related to high releases of catecholamine, which on

412 INDIAN J EXP BIOL, MAY 2000

Ahar

~ Digestion and

Absorption

l EJ

Jatharagani

Excess synthesis of Lipid (Meda)

Low Medagni

Meda/Sneha

Fig. 2-Etiology of atherosclerosis (Ayurvedic view)

reaction with the free iron in the body, produces more hydroxyl radical s and, (C) curry indicates excess intake of fat , which is the best substrate for lipid peroxidation, because of more unsaturated bonds. The mechanism underlies the modulation of various signaling molecules leading to the activation of NFkB, which regulates the expression of genes, responsible for inflammatory factors and chemotactic agents such as Vascular cell adhesion molecule-1 , (VCAM-1 ), endothelial leukocyte adhesion molecule, (ELAM-1) E-selectin, Intercellular adhesion molecu le- 1, ICAM-1 etc.23 (These can be compared to high kapha as hyptothesis) .

For Alzheimer's di sease, there are 3 poss ible causes e.g. free radical theory, amyloid body deposition and Ca2

+ toxicit/ 4. At the molecular level ,

there is activation of NFkB, which enhances the express ion of cyclooxygenase-2 and ultimately the induction of infl ammat ion in the brain ti ssue24

. Beta amyloid bodies are the transformed proteins, produced as the outcome of the defec tive APP (Altered precursor protein)u. Their excess accumulation, degenerates the neural cells. Another factor is the excess of Ca2

+ in the cytoplasm, which is the outcome of hyperactivity of the glutamate receptor and al so the calcium channels on the cell membrane. This high cellular calcium triggers the production of free radicals, and the process of lipid peroxidation and finally neuron damage 18

• Ayurveda believes, that mental disorders are the basic cause for the tncrease tn Vata (Prana/Vata) and the

VATA PITTA KAPHA

Wind Bile P legm

Nervous system Thermogenesis Thermotaxis and formation of preservatives fluid

Hormones Enzymes Immune system

Membrane bound Phosphoryl- Gene expression signal transduction ation processes

Stimulus-receptor, Metabolic steps Defence system interaction

Fig. 3-Proposed hypothesis for developing the subjective parameters to monitor three body humours, described in Ayurv

accumulation of Ama in the brain and nervous tissue. It leads to the inflammation and degeneration of the cells. It is a general principle for the development of Vataj diseases where it is said that the disturbed Vata affects the agni and then produces ama 12

.

For the management of such diseases, Ayurveda describes the use of Rasayana drugs . In this system of medicine, special attention has been paid to thi s branch, as it is anti ageing. It not only recommends for the use of herbal medicine but also includes the code of conduct and life style. Interest ingly a range of herbs have been described for different age groups as rasayan therapy. It opens the channels of the body and leads to the normal metabolism of ingested food . It brings vitality to all the Dhatus (body systems and

TRIPATHI : MOLECULAR APPROACH TO A YURVEDA 413

their organs). It is further recommended for the regular intake of these medicines after the age of 25-30, as the diet supplement to prevent the ageing process2

\ which is considered as a vata mediated disease in the ayurvedic texts .

Rasayanam Cha Yattjjara Vyadhi Naashanam Yatha Amrita Rudanti Cha Gugguluchah Haritaki (Rasayana prevents ageing process)25

On the similar pattern , now a days, the use of antioxidants has come to practice. It is both preventive as well as curative. Specifically the medicines, responsible for the management of free radical medi ated di seases are called antioxidants26

.

They inactivate the reacti ve free radicals, which are spontaneously being produced in the normal physiologica l processes, spec ially in the electron transport chain in mitochondria (ETC). They also chelate the free metals and activate the endogenous antioxidant enzymes at the molecular level, these antioxidants attenuate the activation of NFkB and several other transcription factors, leading to the regulation of gene expression27

, activity of ion channels and different enzymes, specially the kinases, which are important in the signaling cascade28

.

Interestingly, several herbal medicines including many Rasayana drugs have shown the antioxidant property as indi cated by several scienti sts but we are quoting some of the reports from our own laborator/9

-37 fo r ready reference. Like rasayana

drugs , the anti ox idants are also recommended as the diet supplement , to be taken in early age as a preventive measure for different old age diseases. It also acts as the signaling molecule by itself. In thi s way, it appears that most of the properties of free radicals are simil ar to that of Vata as described in Ayurveda. Therefore, a hypothesis could be made that the free radi cals and re lated anti oxidant enzymes and molecules could be treated as one of the objective parameters for the assessment of vata and ojas. Similarly, the other terms of Ayurveda could also be defined as some objec ti ve parameters, as given in Fig. 3.

Acknowledgement The author extends him si ncere thanks to Prof. J.

Mitra, Dr R.D. Sharma, Dr L.D. Dwivedi, Dr C.B.Jha and Prof G.P .Dubey for di scuss ion on the subject.

References I Udupa K N, Neurohumours & body constitution, 1 Res

Indian Med, 8(2): ( 1973) 1-VI.

2 Charak Samhit- chikitsa sutra-57 . 3 Tripathi S N & Tripathi Y B, Medical systems with a holistic

approach, (SNTMF Publi shers, Varanasi, India) 1993. 4 Me Cord J M & Fridovich I. The biology and pathology of

oxygen radicals. Ann Internal Med, 89 ( 1978), 122. 5 Braughlen J M, Duncan LA & ChaseR L. The involvement

of iron in lipid peroxidati on. 1 Bioi Chem, 264 ( 1996) I 0282. 6 Braughlen J M, ChaseR L & Pregenzen J F. Stimulation and

inhibition of iron dependent Lipid peroxidation by desferoxamine. Biochem Biophys Res Commun, 153 ( 1988) 933 .

7 Groot H & Noll T. The role of physiological oxygen parial pressure in lipid peroxidation. Theoretical consideration and experimental evidence. Chem Phys Lipids, 44 (1987) 209.

8 Emerit I & Chance B (Eds) in Free radicals and ageing, (Birkhauser Verl ag Basel, Swetzerland) 1992.

9 Lippman R D, Free radicals induced lipid peroxidation and aging in Hand book of free radicals and anti oxidants in biomedicine, edited by Miquel J, Quintanillia AT and Weber H (CRC Press), 1980.

10 Cheeseman K H & slater T F (eds) Free radicals in medicine, Series of British Medical Bulletin 41 , 1993.

II Di Mascio P & Murphy M E. Antioxidant defence systems : the role of carotenoids tocopherols and thiols. Am 1 C/in Nutr, 53 (199 1) 1945.

12 Charak Samhita: Chapter 28, vata chikitsa. 13 Sinha S & Lieberburg I. Normal metabolism of the amyloid

precursor protein (APP). Neurodegeneration, I ( 1992) 169. 14 Stahl Stephen M, (ed) Cognitive enhancers and

neuroprotective agents, in Essential psychopharmacology (Cambridge University Press) 1996,289.

15 Kemeny M E, Cohen F, Zegans L S & Conant M A Psychosom Med, 51 ( 1989) 195.

16 Harman D. The ageing process: Major risk factors for diseases and death. ?roc Not / A cad Sci USA , 88: ( 1991 ), 5360-63.

17 Ross R. The pathogenesi s of atherosclerosis: A perspecti ve for the 1990' s. Na ture, 3262 ( 1993): 80 1-808.

18 Copper, J Bloom, PE & Roth R H, Th e biochemical basis of neuropharmacology, 7'h editi on Univ Press Oxford , (New York), 1996.

19 Sushruta Samhita, Sutra 15/37 . 20 Tripathi S N Clinical & experimental tri al of guggulu

(Monograph) in Medoroga (lipid di sorders) (Department of Kayachikitsa, IMS, BHU, Varanasi, India) 1975.

2 1 Fuster Valentin (Ed) Syndromes of atherosclerosis, Monograph Series of American Heart Association (Futura Publishing Co, Inc Armonk, New York) 1996.

22 Steingiberg D. Antioxidants and atherosclerosis: A curren t perspective, Circulation, 86 ( 199 1 ): 1420.

23 Tripathi B, Rajavashi sth , Andalibi A, Territo M C, Berliner J A, Navab M , Fogelman A M, & Lusis A J. Induction of endothalial cell expression of granulocyte and macrophage colony stimulating factors by modi tied low density Lipopretein . Nature, 344( 1990) 254.

24 Lukis W 1 & Bazan N G. Strong Nuclear Factor kB - DNA binding parallels cyclooxyagenase-2 gene transcripti on in ageing and sporadic Alzheimer' s disease. 1 Neurosci Res , 53 ( 1998) 586.

25 Sushruta Samhita : Sutra 2 1/16-1 7.

414 INDI AN 1 EXP BIOL, MAY 2000

26 Sies, H (ed) Oxidative stress (Academic Press, London), 1985.

27 Springer, T A & Cybulsky, M L. in Atherosclerosis and coronary artery disease, edited by V Fuster, R Ross and E J Topol, Vol I, 5 11 , (Lippincort-Raven, Philadelph ia) 1996.

28 Caterina R D, Libby P, Peng H 8 , Thannickal V J, Rajavash isth TB , Gimbrone M A, Jr, Shin WS & Li ao J K. Nitric ox ide decreases gtokine- induced endotheli al activati on. J Clin In vest, 96 ( 1995) 60.

29 Tripathi Y 8 , Pandey S Tripathi P & Sharma M. Antiaxidant property of R cordifolia comparison with vi tamin E and parabenzoquinone. Phytother Res, 9 ( 1995) 440.

30 Tripathi Y 8 & Chaurasia S, Effect of S. nuxvomica alcoholi c extract ion lipid perox idation in rat li ver homogenate. lnt J Pharmacognosy, 34 ( 1996) 295.

31 Tripathi Y 8 , Shukla S & Chaturvedi S K, Antoxidant property of Shilajit , Phytother Res, I 0 ( 1996) 268.

32 Tripathi Y 8 & Pandey Ekta. Role of alcoholic extract of shoot of H pe1joratum on LPO and various species of free radicals in rats. Indian J, Exp Bioi, 37 (1 999) 567.

33 Tripathi Y 8, Tripathi Ekta & Upadhayay Ani!. Antilipid peroxidative property of N jatamansi. Indian J Exp Bioi, 34 (1996) 11 50.

34 Tripathi Y 8 , Chaurasia S, Tri pathi E, Upadhaya A & Duby G P. Bacopa monniera an antioxidant, Mechani sm of action . Indian J Exp Bioi, 34 (1996) 523 .

35 Tripathi Y 8 & Singh V P. Antioxidant property of Tamra Bhasma. Indian J Exp Bioi, 34 ( 1996) 66.

36 Tripathi Y 8 , Chaurasia S, Sharma M, Shukla S, Singh V P & Tripathi P. Tea- a strong antioxidant. Curr Sci, 68 ( 1995) 871.

37 Chaurasia S, Tripathi P & Tripathi Y B. Antioxidant & anti­innammatory property of Sandhika, a compound herbal drug. Indian J Exp Bioi, 33 ( 1995) 686.