Content area
Full text
ABSTRACT:
Piperine, a major constituent of Piper nigrum (Black pepper), is one of the well known components in many Ayurvedic formulations. Piperine is most studied bioenhancer because it inhibits drug metabolizing enzymes in rodents and increases plasma concentrations of several drugs, including P-glycoprotein substrates. However, there are no evidences on piperine-vitamin A conjugate to inhibit human CYP450 3A4. In this paper the influence of piperine- vitamin A conjugate to study the metabolism of vitamin A with CYP450 3A4 was investigated. In silico results showed in the present study when piperine was conjugated with vitamin A, CYP450 3A4 was inhibited. This method improved the binding of piperine-vitamin A conjugate with CYP450 3A4 and increased bioavailability of Vitamin A.
KEYWORDS: Bioenhancer, Drug absorption, Cytochrome P450 isoenzymes, Piperine-vitamin A conjugate and docking scores.
INTRODUCTION:
The prevalence of underweight children and vitamin a deficiency xerophthalmia blindness in India is among the highest in the world, and is nearly double that of Sub-Saharan Africa with dire consequences for mobility, mortality, productivity and economic growth [1]. Vitamin A and its derivatives (retinoids) are essential components in vision; they contribute to pattern formation during development and exert multiple effects on cell differentiation with important clinical implications.
It has been known for 50 years that the key step in the formation of vitamin A is the oxidative cleavage of beta-carotene; however, this enzymatic step has resisted molecular analysis. Piperine (1-piperoyl piperidine) which is the active compound in both Piper longum and Piper nigrum is mainly responsible for the bioenhancing activity [2]. The mechanisms for the bio-enhancer activity of piperine have been proposed including DNA receptor binding, modulation of cell signal transduction and inhibition of drug metabolism. Piperine has been demonstrated to increase the serum levels and lengthen the serum half lives of some nutritional substances, such as coenzyme Q10 and beta-carotene [3]. Major categories of drugs that have shown increased bioenhancement include cardiovascular, respiratory, CNS, GIT antibiotics and anticancer. Some examples include tetracyclines, sulfadiazine, vasicine rifampicin, INH, pyrazinamide, ethambutol, phenytoin, phenobarbitone, carbamazepine nimesulide, indomethacin beta-carotene coenzyme Q10 (CoQ10), ciprofloxacin curcumin, dapsone, amino acids, glucose and several other classes of drugs [4-6]. Like Piperine, curcumin could modulate P-glycoprotein and CYP3A4 expression, and in turn modify the pharmacokinetic profiles of P-glycoprotein...