Dr.Gangaadharan, Shri. Darshana Shankar.
Drug design in Ayurvedais viewed in this article in two perspectives: one is based on Ayurvedictheory, wherein modern technology I used to develop convenient dosage forms which are consistent with Ayurvedicpharmaceutical principles. The other perspective is one, which merely uses traditional knowledge as a lead to identify potent bio-molecules. The latter approach does not result in the development of authentic traditional-knowledge products
Tridosha, internal environment, homeostasis
Appreciation of the intrinsic values of a natural substance in its original or natural form with all its molecular complexities, is the corner stone of Ayurvedicpharmacy (Bhaishajya Kalpanaa) This is because Ayurvedicscience has a sophisticated method (Dravya–Gun`a S`haastra) to evaluate the bio-activity of natural products in their pristine` state and does not need to isolate their chemical constituents in order to understand their biological activity.
Ayurveda considers living being (microcosm) as a replica of the larger universe outside the macrocosm. The physician is seen to be like a conveyer-belt between the two, where he/she selects such natural substances from the outer universe and makes only such changes in it, so that the body can assimilate them properly. Just as modern science views objects in terms of their atomic structure, Ayurvedaviews all objects in terms of their Paanchamahaabhautic configuration.
The Paanchabhautika body is a body made out of five states of matter viz. Prithivi (solid), Aapa (liquid), Tejas Thermogenic(plasma), Vaayu (propulsive) and Aakaas`ha (provider room to all), in a certain proportion. The relative proportions of these five contributors determine the properties of every body. Every object has a unique configuration, which is inherent and within this natural configuration it achieves its own equilibrium. Assimilation of natural products from outside can help a body to maintain, disturb or restore its equilibrium.
To understand an unhealthy situation in the body, which manifests as certain symptoms, knowledge of the Panchamahaabhoota physiology of the body is essential. Ill health is essentially due to the change in the inherent proportions of the Panchamahaabhoota_s in a body due to external or internal factor. In the context of living systems the five contributors outlined above are also expressed in terms of three physiological functions viz. Vaata (to move the principle of movement), Pitta (to Metaboliseor transform, the principle of all bio-chemical changes in the body) and Kapha (S`hlisha Aalingane) to keep together, to adhere, to build) and these are collectively known as the Tridosha_s. The challenge of the physician is how to restore the Panchamahaabhautic or Tridoshic balance of an unhealthy body.
The Tridosha_s are the three basic pillars on which the physiology of Ayurvedais constructed.
- Ayurvedic concept of Drug-design:
The drug development in Ayurvedauses the following three principles:
Ksheen`aah Vardhayitavyaah increase the depleted (in relation to the natural configuration) in the body. Vriddhaah Kshapayitavyaah decrease, that are increased in quantity or quality, and Samaah Paalayitavyaah maintain the equilibrium
Any disease whether acute, chronic, degenerative, infectious or functional to occur in the body has to be preceded by one of the two conditions of Ksheen`a or Vriddha of the Tridosha_s or Panchamahaabhoota_s, in the body.
The teaching of the French scientist, Dr. Claude Bernard, the father of experimental physiology, can help to appreciate Ayurvedicphysiology Dr. Bernard coin the word homoeostasis (internal environment). For the first time in the history of modern medicine cocks postulation of organism based disease or origin was challenged by this hypothesis. Dr. Claude proved that unless the bodys internal environment changes to a level where the equilibrium of the body is lost, no diseases can anchor in the body. This probably was the first postulation from modern science similar to the role of Tridosha_s in the genesis of diseases.
The drug design in Ayurvedais thus based on a diagnosis of the extent of internal dis-equilibrium and the selection of natural products needs to be such that they can restore the equilibrium.
Upas`haya is the word used in Ayurvedicparadigm to explain the favourableeffect of remedial measures. These include; Aushadha the medicines, Anna the food that is conducive for the treatment, Vihaara the life style changes that are part of the treatment. (Aushadhaanna–Vihaaraan`aam Upayogah Sukhaavahah).
As per Ayurvedaa drug does not act in isolation, but is an important part of the total regimen, which includes diet and lifestyle changes.
There are also other ecological factors to be considered. Charaka categorically says, `those who treat merely with formulation and not aware of the implication of Des`ha (the habitat in which, the patient lives), Kaala (the time of disease manifestation), Prakriti (Physiosomatic constitution), etc. of the particular person, will be committing mistakes in treatment. Drug development in Ayurvedahas to be done keeping this background in mind.
It is also important to know that the Ayurvedicscience does not limit a physician from developing new dosage forms, new delivery methods and bio-activation of raw drugs in a better way than traditionally available to us.
Charaka and all other Achaarya_s have pointed out that the formulations given by them in texts are only illustrative and are applicable for limited conditions. The formulations can be blindly followed only by those, who are incapable of understanding the principles of Ayurvedicdrug design, (Alpa Buddhinaam Upayogaartham) but the intelligent physician should take these formulations, as examples only, and should go beyond these worked out solutions; to design newer formulations for addressing emerging health conditions. Buddhimataam Udaaharan`a Maatram, and Idam Alam Anuktaartha Dnyaanaaya Dnyaanavataanaam).
- Principles of AyurvedicDrug development.
One can adopt different strategies to design an Ayurvedicdrug. Drug design as per Ayurvedatreatment principles address problems at three levels:
At disease level: To break the chain of pathogenesis
To suppress disease condition
To block progress
To reduce complications or associated diseases
At drug level:
To use drugs having opposite properties to that of diseases
To enhance bio-availability, spread and penetration
To choose dosage forms suitable to enhance absorption
To suggest time of intake of the drugs to enhance its action
At individual level:
To suit Prakritiof the person
To suit local habitat and climate in which the patient resides
As per Ayurveda, a drug should have the following four qualities:
Bahukalpam: the ideal medicine is that which can be made into different dosage forms like powder, tablets, decoction, wines etc.
Bahugun`am: it should have multiple actions like while improving the peristaltic movement it also helps in digestion
Sampannam: the medicine should retain all its natural properties intact even after processing and for the duration of its shelf life.
Yogyam: is the appropriateness of a medicine in a given condition, for example even if a medicine chosen is very potent in its quality and actions, but is not administered for the right condition, then it is not Yogyam in that situation.
- Some universal applications:
There are also certain medicines, which are specific for certain diseases, and can be used in the disease irrespective of the Prakriti, Des`ha and Kaala etc. of the person. These medicines are known as Vyaadhi Vipareeta. For example in diarrhea, Paat`haa (Cessamplus Parera) which is Stambhana (anti-peristaltic), Acacia Katachu(Khadiram) in skin diseases, or turmeric in diabetics. These medicines act universally against the said diseases irrespective of the Dosha and other characters.
- The Modern approach:
Drug development based on natural products is a fast growing area, due to the limitations of discovering newer synthetic molecules. In the conventional system drug development is based on the Pharmaco-kinetics and dynamics. A drug according to this definition is a biologically active molecule, which can act or react with a biological unit in the body to bring in a well-defined result within the given time. So drug in western medicine is like a bullet aimed at a given target, which will hit the target even while it may have other side effects. In other words, it can be said that drug by this definition is drug without a holistic intelligence.
- The holistic Nature of AyurvedicMedicine:
In Ayurvedaa drug is that entity, which will bring in lost equilibrium of the Panchamahaabhoota_s (physiological functions) in the body and in the process correct the damages, brought by the disease. Here the drug acts with holistic intelligence. For example, when Triphalaa is taken as a purgative, it removes the unwanted materials from the system but does not; in any way disturb the intestinal flora in the process. Also when Triphalaa is taken in the appropriate dose while improving the bowel movement, it also helps to improve eyesight, increase immunity and has an anti-ageing property.
- Ayurveda: A New Discovery Engine
Combining the strengths of the knowledge base of traditional systems such as Ayurvedawith the dramatic power of combinatorial sciences and high thorough-input screening will help in the generation of structure-activity libraries. Ayurvedicknowledge and experiential database can provide new functional leads to reduce time, money and toxicity-the three main hurdles in the drug development. These records are particularly valuable since effectively these medicines have been tested for thousands of years on people. Efforts are underway to establish Pharmaco-epidemiological evidence-base to Ayurvedicmedicines, safety and practice. Development of standardized herbal formulations is underway as an initiative of the Council for Scientific and Industrial Research (CSIR) New Millennium Indian Technology Leadership Initiative (NMITLI). Randomised controlled clinical trials for Rheumatoid and Osteo-arthritis.
Hepatoprotective, Hypolipedemicagents, Asthma, Parkinson`s disease, and many other disorders have reasonably established clinical effects. A review of some exemplary evidence-based researches and approaches has now resulted in wider acceptance of Ayurvedicmedicines. Thus the Ayurvedicknowledge database allows drug researchers to start from a well-tested and safe botanical material. With Ayurveda, the normal drug discovery course of `Laboratory to Clinics` actually becomes from `Clinics to Laboratories` a true Reverse Pharmacology Approach.
In this process Safety remains the most important starting point and efficacy becomes a matter of validation. Globally, there is a positive trend towards holistic health, integrative sciences, system biology approaches in drug discovery and therapeutics that has remained one of the unique features of Ayurveda. A golden triangle consisting of Ayurveda-modern medicine Science will converge to form a real discovery engine that can result in newer, safer, cheaper and effective therapies. It will be in the interest of pharmaceutical companies, researchers and ultimately the global community to respect traditions and build on their knowledge and experiential wisdom.
- The vast resources in Ayurveda:
Nearly 5,800 clinical signs and symptoms are available in Ayurvedictexts. Effects of season, time and environmental condition as per Ayurvedicchrono-biology principles need to be considered to advise lifestyle modifications followed by dietary advice. More than 1700 species of plants, nearly100 minerals and over 100 animal products comprise the AyurvedicPharmacopoeia. Thousands of single, multiple combinations and processed formulations are described in Ayurvedicliterature along-with details of drug actions. The extent of this database is very large and it can be best managed with help of suitable computer and software.
- Drug Discovery: Intentional Not Coincidental:
In the sequence of their appearance, the scientific disciplines involved in drug discovery were: chemistry, pharmacology, physiology, microbiology, biochemistry and molecular biology. It can be shown that new therapeutic classes of drugs like muscle relaxants; diuretics, L-Dopa, antibiotics, recombinant proteins, monoclonal antibodies and others were generated on the basis of scientific opportunities rather than therapeutic need. All of these drugs were created within the confines of a chemical paradigm of medicine and drug therapy. We are now witnessing the entry of a new informational paradigm into medicine that is most prominently represented by genomic sciences, This paradigm will bring two important changes to the therapy of diseases, First, molecular biology has matured to such a degree that it can now study complex genomes and their functionality in complex organisms such as humans. Therefore, results from these studies no longer have to be translated into the context of medicine: they are already within this context, Secondly, drug therapy that used to be largely symptomatic, will now aim at targets, which are closer to the causes of diseases than previously. Therapeutic progress, which used to be indirect, conjectural and coincidental, is about to become more directed, definitive and intentional. The future drug discovery will be more often based on intent rather than coincidence. Proper bio prospecting of medicinal sources will be an important factor.
- Conclusion / Recommendation:
To conclude it can be said that in the new era of drug development, based on natural products, there can be two paths:
Once the traditional (western) methods of drug discovery based on active principles and hit the trial method and the other is intentional based on a sound understanding of the paradigm of natural products action in the body based on Ayurvedicprinciples.
The latter one has got greater chances of success and also has lesser time bar for development as it is based on the clinical activity.
Even here the health care product has to be divided into the following categories:
- Cosmoceutical, as against cosmetics: the product, which brings in permanent physiological changes in the body, for example Kumkumaadi Tailam for skin fairness. This can be of Over the Counter (OTC) type.
- Functional foods
- Promotive medicines like in the areas of;
Free radical scavenging
- In the areas of structural diseases like chronic kidney diseases, and Diabetic Retinopathy, etc, a package of management has to be developed where the drug will be an important component.
Ayurveda says that the knowledge of whole cannot be accrued from the knowledge of the part. This means that we have to take the medicine as whole and the person also as a whole. Charaka, categorically disapproves treatment of the part. Ayurvedasays there are two kinds of treatments: one is S`huddha, (pure) and the other one As`huddha (impure). The pure treatment is that, which while alleviating the disease will not become cause for any other disease. Impure treatment is that, which while curing the disease may become causative factor for other diseases.
This perfectionist approach of Ayurvedahas to be highly appreciated. Ayurvedastrongly believes that a medicine given to the body should be fully assimilable to become part of the bodily elements. Anything that cannot fit into the definition is not regarded as a medicine in Ayurveda.
The science of drug development in Ayurvedahas to be seen from this broader framework so that a functionally superior health care product, based on natural substances can be developed. This reminds one of the enlightened words of the late Prof. Dhyaniof Gujarat AyurvedicUniversity, Jamnagar. He always says, Take the medicine as a whole and treat the person as a whole.
The potential of traditional knowledge in contributing to the development of the healthcare products of contemporary value, is a promising area and has to be explored by well-informed Ayurvedicscientists, if new products of any value have to be developed.
The issue here is one of direction, not one of scientific capacity. Ayurvedaand all other traditional knowledge systems are not in the mainstream science, not because they lack internal strength or rigor, but because of their politicosocial marginalization.
Indian scientists of western and indigenous sciences need to join hands and usher in a new era of creativity that draws inspiration from our rich medical heritage
We acknowledge thankfully the suggestions given by Dr. S. N. Venugopal, and Dr.Ashwini Mathur.
- Charaka Samhitaa Sootrasthaana
- Maadhava Nidaanam Chapter 1-Ver.8
- Charaka Samhitaa Chikitsaa, Chapter 30 Ver.32
4/5/6 Dr. Bhushan Patwardhan, Current Science-October, 2003
- Charaka Samhitaa Vimaana sthaana Chapter 5
Last updated on March 8th, 2021 at 11:13 am