Effects of capsaicin and dihydrocapsaicin on human and rat liver microsomal CYP450 enzyme activitiesin vitroandin vivo

Abstract

Capsaicin and dihydrocapsaicin, the two most abundant members of capsaicinoids in chili peppers, are widely used as food additives and for other purposes. In this study, we examined the inhibitory potentials of capsaicin and dihydrocapsaicin against CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4/5 activities in human liver microsomes. The effects of these two capsaicinoids on CYP450 enzymes were also evaluated in vivo in rats. The results demonstrated that capsaicin and dihydrocapsaicin moderately inhibited five isozymes (IC₅₀) values ranging from 4.4 to 61.8 μM), with the exception of CYP2E1 (IC₅₀ > 200 μM). Both capsaicinoids exhibited competitive, mixed, and noncompetitive inhibition on these isozymes (K (i) = 3.1 ± 0.5 - 78.6 ± 8.4 μM). Time-dependent inhibition of CYP3A4/5 by capsaicin was found. After multiple administrations of capsaicin and dihydrocapsaicin (1, 4, and 10 mg/kg) to rats, chlorzoxazone 6-hydroxylase activity and the expression of CYP2E1 were increased in liver microsomes. Our findings indicated that the possibility of food-drug interactions mediated by capsaicin and dihydrocapsaicin could not be excluded, and provided the useful information for evaluating the anticarcinogenic potentials of these two capsaicinoids.

Transient Receptor Potential Vanilloid 1 Activation Enhances Gut Glucagon-Like Peptide-1 Secretion and Improves Glucose Homeostasis

“…It is unknown whether there is interaction between capsaicin and DPP-4 inhibitors. Several studies show that capsaicin, but not DPP-4 inhibitors (except saxagliptin), can inhibit cytochrome P450 (CYP 3A4/A5) enzymes (48–50). Thus, in general, interactions between DPP-4 inhibitors and capsaicin are absent or minor.…”

The Potential Antitumor Effects of Capsaicin

“…Capsaicin is mainly metabolized in the liver through cytochrome P450-dependent reactions and peroxydase enzymes, producing three major metabolites, 16-hydroxycapsaicin, 17-hydroxycapsaicin, and 16, 17-hydroxycapsaicin, and is scarcely excreted in the urine (Suresh and Srinivasan 2010). Although many enzymes may play some role in hepatic drug metabolism, cytochrome P450 enzymes are quantitatively the most important, and it has been proposed that many drug-drug interactions result from the alteration (increase or decrease) in the activities of these enzymes (Zhang et al 2012;Zhai et al 2013). However, Babbar et al demonstrated that at concentrations occurring after ingestion of chili peppers or topical administration of a high-concentration patch, capsaicin did not cause direct inhibition of any CYP enzyme (Babbar et al 2010).…”

Evaluation of the effect of apatinib (YN968D1) on cytochrome P450 enzymes with cocktail probe drugs in rats by UPLC–MS/MS

“…The cytochrome P450 family includes many isoenzymes, such as CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4, which metabolize over 90% of clinical drugs, and the functions of enzymes of the same family are similar [2][3][4]. Assessing drug-drug interactions (DDIs), especially the evaluation of the effect of a new drug on the CYP450 enzyme activities, is essential and important to understanding toxic and inhibitory effects [5].…”