Bioenhancers from mother nature and their applicability in modern medicine

Concept of bioenhancers or biopotentiators was first time reported in 1929 by Bose. A bioenhancer is an agent capable of enhancing bioavailability and efficacy of a drug with which it is co-administered, without any pharmacological activity of its own at therapeutic dose used. Development and consequent isolation of these molecules, such as piperine and quercetin, is considered as scientific breakthrough. A fixed drug combination (Risorine) of rifampicin, isoniazid, and piperine is the result of this research. It contains almost 60% less dose of rifampicin because of its increased bioavailability and it also prevents resistance. This concept is mentioned as yogvahi in ayurveda and was used to increase the effect of medicines by increasing oral bioavailability, decreasing adverse effects and to circumvent parenteral routes of drug administration. More such useful and economically viable drug combinations can be developed by integrating knowledge of time tested ayurveda with modern methods of research. This review is an account of these bioenhancers, available from the natural resources.

The concept of bioenhancers or biopotentiators is new to the modern science. It was first time reported by Bose in 1929, who described the increase in the antiasthmatic effects of vasaka (Adhatoda vasica) leaves by the addition of long pepper to it.[1] The development and consequent isolation of these molecules is considered as a scientific breakthrough. A bioenhancer is an agent capable of enhancing the bioavailability and efficacy of a drug with which it is co-administered, without any pharmacological activity of its own at the therapeutic dose used. They tend to decrease the dose of active drug required for the optimal endpoint of the treatment strategy, bypassing the need to use injectable routes of drug administration to a larger extent, might help in overcoming the resistance to antimicrobials and saving the precious raw materials for the manufacturing of medicines. Such fixed drug combinations (FDCs) are economically viable too.

The concept of bioenhancer is called Yogvahi in Ayurveda. Synergism, that is, increase in the action of one biomolecule by another unrelated chemical is the hallmark of polyherbal formulations of ayurveda. Yogvahi is used to enhance the bioavailability, tissue distribution, and efficacy of drugs, especially with poor oral bioavailability and decreasing the adverse effects in the process. Specific yogvahis or bioenhancers are termed as Anupaan and Sehpaan. Anupaan means food concomitantly given with the medicament to increase the effect of the medicament, such as “Amrit Dhara” drops used for gastrointestinal diseases are ingested after putting the drops over sugar, to increase their potency. Sehpaan means that the vehicle, which is used during the manufacturing of the medicament increases the effect of the medicament, like for panchgavya ghrit and brahmi ghrit, clarified butter/ghee/ghrit is used. General yogvahis routinely used in many ayurvedic preparations are trikatu [Piper longum (long pepper/ pippali), Piper nigrum (black pepper/ kali mirch) and Zingiber officinale (ginger/ adrak)],[2] sesame/til, gold/ swarn bhasam, and heerak bhasm[3] and cow urine distillate.[4]

Modern researchers are increasingly showing interest toward the improvement of bioavailability of a large number of drugs by addition of various herbs with bioenhancing properties. Of the promising approaches being used are absorption enhancers, prodrugs, micronization, and manufacturing of delayed release, timed release, sustained release capsules and spansules, and permeability-enhancing dosage forms, such as liposomes and emulsions. Recently, the application of P-glycoprotein (P-gp) inhibitors in improving oral drug delivery has gained special interest.[5,6]

In oral drug delivery system, the co-administration of therapeutic agents with natural compounds possessing absorption improving activities, has also garnered great interest. Active components of these natural compounds with bioenhancing properties, such as piperine, quercetin, genistein, naringin, niazeridine, lysergols, capmul, Callistemon rigidus, Carum carvi, sinomenine, glycyrrhizin, and nitrile glycoside, are being isolated for their possible use along with modern medicines.

 

References

1. Varshneya C. Use of herbal bioenhancers in animal health care. [Last accessed on 2010 Nov 22]. Available
2. Sharma PV. Dravyaguna-Vijnana: Vegetable drugs.2nd ed. Varanasi: Chaukhamba Bharati Academy; 2009. p. 109. (121,331-5,362-5).
3. Pathak R. Ayurved Sar Sangrah.12th ed. Kolkatta: Shri Baidyanath Ayurved Bhavan Limited; 2010. pp. 176–9. (212-24). 
4. Randhawa GK. Cow urine distillate as bioenhancer. J Ayur Integ Med. 2010
5. Breedveld P, Beijnen JH, Schellens JH. Use of P-glycoprotein and BCRP inhibitors to improve oral bioavailability and CNS penetration of anticancer drugs. Trends Pharmacol Sci. 2006;27:17–24. 
6. Kang MJ, Cho JY, Shim BH, Kim DK, Lee J. Bioavailability enhancing activities of natural compounds from medicinal plants. J Med Plants Res. 2009