Capsaicin induces CYP3A4 expression via pregnane X receptor and CCAAT/enhancer‐binding protein β activation

Abstract

From these data, we conclude that capsaicin induces CYP3A4 expression in vitro and in vivo. This induction was achieved by the activation of hPXR and C/EBPβ. Our results suggest that capsaicin might induce CYP3A4 expression; thus, exposure to capsaicin may increase the metabolism of CYP3A4 substrate and potentially cause food-drug interactions.

Differences inCYP2C9Genotype and Enzyme Activity Between Swedes and Koreans of Relevance for Personalized Medicine: Role of Ethnicity, Genotype, Smoking, Age, and Sex

“…However based on our result, it is plausible to assume that CYP2C9 enzyme in Koreans is rather induced by regular dietary constituents present in Korean food that are not commonly consumed in Sweden. Actually a recent study from Korea reported that capsaicin, the principal pungent ingredient in hot red and chili peppers, induces CYP3A4 expression both in vitro and in vivo via human pregnane X receptor (hPXR) and C/EBPb activation (Han et al, 2012). Another study from Japan also reported the induction of p-glycoprotein (P-gp) by capsaicin (Okura et al, 2010).…”

“…Another study from Japan also reported the induction of p-glycoprotein (P-gp) by capsaicin (Okura et al, 2010). The authors concluded that regular exposure to dietary ingredient containing capsaicin increases the metabolism of CYP3A4 substrate and P-gp potentially to cause fooddrug interactions ( Han et al, 2012;Okura et al, 2010). Hot red and chili peppers are common spices in regular Korean, Indian, Thai, and Ethiopian food.…”

“…Since induction of both CYP2C9 and CYP3A enzymes by drugs such as rifampicin, hyperforin (found in St. John's wort), and phenobarbital is mediated via activation of hPXR (Chen et al, 2004), it is highly likely that regular dietary components such as capsaicin, which also is a ligand for hPXR (Han et al, 2012), induce CYP2C9 enzyme (in Koreans), but this needs further investigation. One limitation of this study is the lack of further information on the daily basic diet consumed by the Koreans and Swedes.…”

Nonivamide, a capsaicin analog, increases dopamine and serotonin release in SH-SY5Y cells via a TRPV1-independent pathway

“…Inhibition of the TRPV1 receptor demonstrated that release of these neurotransmitters is mediated by a nonselective TRPV1 cation channel , which is permeable to Ca 2+ ions and responsible for triggering dopamine and serotonin release in neural cells . Capsaicin promotes Ca 2+ influx via the TRPV1 cation channel and promotes phosphorylation of the downstream signaling factor Ca 2+ /calmodulin‐dependent protein kinase II , which might be a mechanism of capsaicin‐induced TRPV1 activation. Moreover, capsaicin also stimulates Ca 2+ ‐release from a ryanodine‐sensitive intracellular calcium store .…”

“…Capsaicin promotes Ca 2+ influx via the TRPV1 cation channel and promotes phosphorylation of the downstream (1) and nonivamide (2). signaling factor Ca 2+ /calmodulin-dependent protein kinase II [11], which might be a mechanism of capsaicin-induced TRPV1 activation. Moreover, capsaicin also stimulates Ca 2+release from a ryanodine-sensitive intracellular calcium store [12].…”