Samyoga

Ayurveda represents a huge source of traditional knowledge of drugs, formulations developed in ancient times. Crossing the barrier of the time its relevance is continuing in-spite of changes in the environment, lifestyle, and culture also disease pattern. The philosophy of treating a system or body is gaining relevance as we develop from a reductionist approach to “systems” the approach in this post-genomic era. Yet our understanding of Ayurveda is only at its beginning.

Rise of Combination therapies

Multimodal treatments or multi-target approaches are increasingly applied to treat complex diseases in different disciplines of medicine–mainly based on empirical knowledge. There is a need to elucidate and define further the combinatory actions in the theoretical basis, experimental design and quantification of synergy at different dose and effect levels, including optimal combination ratios or sequences and the prevention of potential adverse events. Therefore, efforts should be made towards the development of personalized medicine by approaching the effect of drug combinations on the patients with a systems approach. Thus exploring synergistic actions/effects of specified Traditional Indian natural compounds, including the "mechanistic" principles of synergy and the use of network analysis and suitable modern bioinformatics approaches which will lead to developing phytopharmaceuticals or the fixed-dose formulations based on leads from Traditional Indian medicinal plants. 

Synergy in Ayurveda

In terms of pharmacology, we correlate the synergy phenomenon by an over-additive effect of two or more drugs or substances when administered in combination. Synergy is explored by combinatory treatments of compounds for synergistic effects based on different pharmacological definitions of “synergy” with an emphasis on the combination index based on the combination index theorem of Chou and Talalay that is derived from the median-effect equation and the mass-action law. Ayurveda the traditional medicine of India focuses on synergy where the knowledge of multi-component actions is a key concept. They term it as ‘samyoga’, or the knowledge of synergistically combining ingredients for the maximum of safety and efficacy. The Ayurvedic literature ‘Sarangdhar Samhita’ highlighted the concept of poly-herbalism to achieve greater therapeutic efficacy. Synergism plays a major role in the therapeutic efficacy of herbs or herbal formulation. The multi-component nature of these medicinal herbs and traditional formulations makes them particularly suitable for treating complex diseases and offers great potential for exhibiting synergistic actions [2]. Ayurveda has defined synergy in “Charak Samhita” as “Yogavahi” which is the quality of a substance to be associated (samyoga) with.

Anupana, Sehapana

Pharmacokinetic synergism in Ayurveda has been elaborated by the concept of bioenhancers or biopotentiator. It was first observed to explain the enhanced anti-asthmatic effects of Adhatoda vasica (‘Vasaka’) leaves by the addition of Piper longum L. This concept of bioenhancer is called ‘Yogvahi’ (Yog- drug complex Vahi- transporter) in Ayurveda which enhance the bioavailability, tissue distribution, and efficacy of drugs, especially with poor oral bioavailability and decreasing the adverse effects. Specific ‘yogvahi’ or bioenhancers are termed as ‘Anupana’ and ‘Sehpaan’. Pharmacokinetic synergy is essentially included and preserved in the concept of ‘Anupana’ (the carrier which the herbal medicines are prescribed with such as hot water, milk, honey, etc.) they emphasize which under Ayurveda therapeutics. The ancient texts like ‘Charaka Samhita’, ‘Sushruta Samhita’ have defined ‘Anupana’ (carrier properties) of food or anything that is administered with medicine (oushadha). The medicine becomes more potent when given with a suitable Anupana which may be personalized according to the avastha (stage) and bala (strength) of the rogi and roga (patient and disease). Whereas Sehpaan implies, the vehicle used during the manufacturing of the medicine to increase its effect, like for example ‘panchgavya ghrita’ and ‘brahmi ghrita’; ‘Ghrita’ (they commonly use clarified butter. General ‘yogvahi’ (drug transporters) which are routinely used in many Ayurvedic preparations are ‘trikatu’, sesame oil (‘til’) or calcinated gold (‘swarna bhasma’).

Success story

Traditional medicine inspired the identification and isolation of piperine, from Piper longum L.  — a natural bio-enhancer molecule. Risorine, a fixed dose composition of Rifampicin, Isoniazid, and Piperine has been marketed for the management of tuberculosis, resulting in a decrease of the Rifampicin dose from 450 to 200 mg, with 60% improvement in its bioavailability [6]. Piperine acts by suppressing P-gp and cytochrome P450 enzymes, which counteract the metabolism of rifampicin via these proteins, thus enhancing the oral bioavailability of Rifampicin. The intestinal production of glucuronic acid is also decreased increasing bioavailability. They found it to increase the bioavailability of various drugs from 30% to 200%.