The Philosophy of Ayurveda and Beyond

Arunabha Ray and Kavita Gulati

Department of Pharmacology Vallabhbhai Patel Chest Institute Faculty of Medicine, University of Delhi, Delhi (India)

Ayurveda
Indian traditional system of medicine

Herbo-mineral system of medicine practiced for more than 3000 years

This holistic system of medicine is based on the inherent ability of the human body to rejuvenate, to heal and to restore its natural balance

It uses the time proven concepts of regulated diet and a healthy lifestyle, supported with remedies and treatments that are safe, effective and affordable

Ayurveda
AYUR = Life and VEDA = Science/knowledge

Ayurvedas theory of humoral pathology says that the human body is composed of Trisdoshas the three humors Vata, Pitta and Kapha
The Tridoshas in equilibrium are called the Tridhatu The body in which these three humors are in state of equilibrium enjoys perfect health; their disequilibrium causes ill health or disease

The Three doshas (humors)

Vata, Pitta and Kapha (or Doshas) are three basic elements of the body The basic concept of Ayurveda says that each individual has them in a certain proportion in their bodies

Tridoshas
The activity of Vata is that of transportation of taking one thing from one part of the body to the other Kapha does the work of cementing, keeping the body together

Pitta is related to digestion

A state of well being is thus an equilibrium of all these three things

An examplethe spinning top

The spinning top While it is in motion it seems to be spinning perfectly vertical perfect health

The moment it is disturbed it starts tilting over and losing balance, this is a deviation disease If it continues spinning and stops of its own inertia, this is natural - this could be compared to a natural death

Indian (Hindu) Philosophy

Indian philosophy may be divided in to two streams Astika and Nastika The Astikans believed in god , a life after death and the supreme authority of the Vedas - the sacred scriptures of Hinduism The Nastikans (non-believers) negated all these holy concepts The Astika stream has six main darsanas or philosophies, of which the Sankhya philosophy has influenced Ayurveda the most in developing its fundamental theory of humoral pathology

In summary
The gist of Ayurveda philosophy is related to the soul or individual consciousness The structural arrangement or the functional arrangement of the body is in synchrony with the external environment Its a very harmonious relationship taking into account individual constitution, effect of time, effect of age, diet and habits acquired over a period of time This is precisely how Ayurveda looks at life

Ayurveda Rasayana
Rasayana : an important component Refers to therapeutic regimens It deals with conservation, transformation and revitalization of energy Rasayana describes herbal preparations that promotes a youthful state of physical and mental health and happiness

Rasayana
Rasayana herbs have high levels of both safety for daily use and effectiveness across all age barriers They are normalizers of disrupted physilogical homeostasis (? Hans Selye`s concept of Stress) Rejuvinators or immunomodulators Some similarity with modern day adaptogens considerable overlap Integration of Ayurvedic concepts with scientific validation the order of the day

Herbal Drug Research

Emerging area of research in pharmacology and medicine globally New drug development from herbal sources has been a thrust area in recent years Effective alternative/complimentary therapy in several diseases Safety profile mostly being well documented Scientific methodology being adopted to delineate molecular mechanisms (eg. systems biology approach) Interactions between traditional and modern medicine

Adaptogens
Adaptogens have a normalizing effect on the body and are capable of either toning down the activity of hyperfunctioning systems or strengthening the activity of hypofunctioning systems

It is claimed that adaptogenic herbs are unique from other substances in their ability to balance endocrine hormones and the immune system, and they help the body to maintain optimal homeostasis

Adaptogenic herbs
Adaptogens with significant levels of scientific research confirming their use include: Ashwagandha (Withania somnifera) Holy Basil (Ocimum sanctum) Guduchi (Tinospora cordifolia) Licorice (Glycyrrhiza glabra) Amla (Emblica officinalis)

Traditional and modern medicines : complimentary roles

Reverse pharmacology Modern biological approaches Explore novel molecular mechanisms Systematic preclinical toxicity studies Clinical Trials and Pharmacovigilance Validation of herbal drug effects Golden Triangle Project (GTP) in India

Reverse Pharmacology
Experimental evaluation of clinically observed findings, seen specially with herbal agents Reverse pharmacology as an alternative path for new drug development

Reverse pharmacology (Ayurvedic) drug action

correlates

herbal

A practice which was successfully employed in the past (eg. Reserpine) and is being more scientifically implemented now

Ocimum sanctum (Tulsi)

Ocimum sanctum (Holy Basel) or Tulsi Most common and revered plant in the Indian household Healing herb with sacred implications in this part of the subcontinent In Ayurveda : role in enhancing immune and metabolic function and in respiratory disorders

Effects of O.sanctum (OS) on behavior and plasma corticosterone in stressed (RS) rats
Treatment (mg/kg) Controls RS OAE in the OAT in the CorticosterEPM (%) EPM (%) one (ug/dl) 28.7 6.0 15.0 2.8 23.6 3.9 9.0 2.2 * 4.8 1.0 * 41.6 6.6 *

OS (50) + 17.2 5.2 a 7.0 2.2 33.0 8.1 RS OS (100) + 30.3 4.4 a 12.4 + 1.9 a 25.6 3.3 a RS
* p< 0.05 ( vs. no RS ) ; a. p < 0.05 ( vs. RS)

Effects of O. sanctum on stress gastric ulcers

Treatment (mg/kg) Controls RS OS (50) + RS Mean Ulcer number 0.6 0.2 7.8 1.6 * 4.8 1.2 a Mean Ulcer severity (mm) 0.2 0.04 2.8 0.6 * 2.0 0.6

OS (100) + RS

2.1 0.3 a

0.8 0.2 a

* p< 0.05 ( vs. no RS ) ; a. p < 0.05 ( vs. RS)

Effects of O.sanctum on adaptive immunity

Treatment (mg/kg) Controls Antibody titre (-log2) 6.6 0.6 DTH response (%) 20.2 3.5

RS
OS (50) + RS OS (100) + RS

3.4 0.4 *
5.0 0.6 7.0 1.0 a

12.6 5.0 *
19.6 6.6 a 22.7 4.2 a

* p< 0.05 ( vs. no RS ) ; a. p < 0.05 ( vs. RS)

OS and stress responses

OS leaf extract reversed RS induced neurobehavioral suppression in the elevated plus maze test The herbal extract lowered RS-induced elevations of corticosterone The severity of stress induced gastric erosions were attenuated by OS

Stress-induced suppressions of adaptive immunity were also reversed by this agent

Azadirachta indica (AI) - Neem

Indian lilac, Azadirachta indica A. Juss (Latin) Highly esteemed, widely prevalent tree in Indian subcontinent (Wonder tree) In Ayurveda : Sarva Roga Nivarana Releases large amounts of oxygen (photosynthesis) as compared to others Air purifier All parts of the plant are beneficial (root, seeds, bark, stem, leaf, flower)

Azadirachta indica (Neem) and stress markers

%

180 160 140 120 100 80 60 40 20 0 EPM activity Corticosterone C RS AI+RS DZP+RS

Effects of AI (Neem) Leaf Extract on Immune responses in normal and stressed rats
Treatment Antibody Titre Footpad thickness (mg/kg) (-log2) (Rt-Lt Paw) ---------------------------------------------------------------------------Vehicle (no RS) AI(100) RS 6.7 0.5 7.0 0.3 4.1 0.5* 0.072 0.006 0.093 0.003 0.040 0.010*

AI(100) +RS 6.3 0.3a 0.077 0.020a ---------------------------------------------------------------------------* p< 0.05 ( vs. no RS ) ; a. p < 0.05 ( vs. RS)

Stress, Immunity and AI

RS suppressed humoral and cell mediated immune responses which was attenuated/reversed after AI pretreatment Immunized rats showed higher antibody titres after AI treatment (no RS) AI also potentiated IgG and IgM levels in normal animals

AIan adaptogen ?
Xenobiotic-induced immune suppression was also reversed by AI leaf extract RS potentiated xenobiotic effects on immune markers in a AI reversible manner AI influenced GGT activity in lymphoid cells AI could be an important immune regulator during emotional and environmental stress AI : A Rejuvinator or Adaptogen ?

Dopamine (DA) and stress

The role of DA and its receptors in the modulation of as stress responses is reported DA agonists protect whereas, DA antagonists aggravate stress responses Interactions of DA with other modulators/transmitters suggested during stressful stimuli

In view of this, the possible role of DA in anti-stress effects of adaptogens were evaluated

Effects of dopamine depletors and receptor blockers on adaptogen effects on stress (RS) markers
_________________________________________________ Treatment Antibody Titre Gastric Ulcers (mg/kg) (-log2) ( mm) -------------------------------------------------------------------------Vehicle (no RS) 6.7 0.5 0.04 0.02 RS 3.8 0.4* 2.8 0.6*

OS + RS
AI + RS -MT + OS + RS

6.0 0.6a
5.8 1.0a 4.0 0.4

1.0 0.2 a
0.6 0.3a 3.6 0.8

Hal + AI +RS 4.8 1.2 3.0 0.3 -------------------------------------------------------------------------* p< 0.05 ( vs. no RS ) ; a. p < 0.05 ( vs. RS)

Summary
Both OS (Tulsi) and AI (Neem) leaf extracts attenuated stress (RS) induced immune suppression and gastric ulceration Pretreatment with DA depletors / blockers prevented these anti-stress effects of the herbs Such herb-drug interactions are suggestive of the role of DA in the effects of the adaptogens

There are several other conditions for which such studies are ongoing

Conclusions
Ayurveda is much more than a mere philosophy

The use of reverse pharmacology approach and novel techniques are being used effectively to validate some traditional Ayurvedic drug effects
Pharmacological studies with adaptogens provide a good example

Such integration between traditional and modern concepts, i.e. philosophy with science, can be the key to new herbal drug development

Acknowledgements
Prof. P. Sen Late Prof. S.K. Bhattacharya Dr. P.C. Maity Dr. C.K. Katiyar Prof. B.D. Banerji All students and staff members in my lab Dabur Research Foundation (India)

Thank you