Mechanisms of Action

There are numerous documented reports on bio-enhancing feature of a number of therapeutic agents as well as phytochemicals by piperine. The mechanisms by which piperine exerts the drug bioavailability may be explained by following possible explanations:

Mechanism of action

Piperine’s Effect on Efflux Mechanism

In Caco-2 cells (human colon carcinoma cell lines), piperine has been found to inhibit the P-glycoprotein (P-gp)-mediated transport of drugs, such as digoxin and cyclosporine A.

It has also been indicated that dietary piperine could affect the plasma concentrations of P-gp and metabolizing enzyme CYP3A4 substrates in humans, in particular if the drugs are administered orally (Bharadwaj et al., 2002).

Also oral administration of piperine at a dose of 112 µg/kg for 14 days led to increased intestinal P-gp level with reduced hepatic P-gp, while the renal P-gp level were unaffected in rats (Han et al. 2008).

P-glycoprotein(P-gp), transmembrane permeability glycoprotein, is a memeber of ATP binding cassette (ABC), an enery dependent efflux transporter driven by ATP hydrolysis. P-gp is extensively distributed in the intestinal epithelium, hepatocytes, renal proximal tubular cells, adrenal glands and capillary endothelial cells. P-gp pump can alter the intestinal absorption, or the renal and billiary excretion of various P-gp substrates such as lipids, xenobiotics, steroids, peptides, chemotherapeutic agents and natural compounds.

P-gp inhibition is one of the possible mechanisms for piperine's bioavailability enhancing activity.

Piperine’s Effect on Glucuronidation

Piperine was found to modify the rate of glucuronidation by lowering the endogenous UDP-glucuronic acid content and also by inhibiting the transferase activity (Singh et al. 1986).

Piperine was also found to inhibit UDP-glucose dehydrogenase (UDP-GDH) activity in both liver and intestine via non-competitive inhibition
(Reen et al.,1993).

Glucuronidation is addition of glucuronic acid to a substrate and it is involved in xenobiotic metabolism.

Glucuronides are more water soluble and human body uses glucuronidation for eliminating substances/drugs from the body.

Thermogenesis

A thermonutrient such as BioPerine^® would potentially improve the process of nutrient absorption by enhancing thermogenesis.

The leading theory of food-induced thermogenesis relates to the autonomous nervous system. The autonomous nervous system is represented by two main receptors in the gastrointestinal tract, the alpha and beta adrenergic receptors.

Metabolic process that generates energy at the cellular level in the human body is called thermogenesis.

Thermogenesis has been identified as a key factor in weight management; it has also been identified as playing an integral role in utilizing the daily food and nutrients that the human body consumes.

Most of the food or thermonutrient-induced thermogenesis is facilitated by beta receptors, which include a compound known as cyclic adenosine 3’, 5’ monophosphate (cAMP). The role of cAMP as a "second messenger" to the hormonal and enzymatic actions in the body is well recognized. When thermogenesis occurs, the demand for fresh nutrients to sustain the metabolic processes rapidly increases.

Piperine has been found in independent studies to stimulate the release of catecholamines, thermogenic hormones, whose action is made possible by the presence of cAMP. However, the nature of the thermogenic response mediated by catecholamines is relatively short-lived.