Bioactive components of Glycyrrhiza uralensis mediate drug functions and properties through regulation of CYP450 enzymes

Abstract

Glycyrrhiza uralensis (G. uralensis) is a common medicinal plant that has mainly been used to modulate the pharmaceutical activity of herbal medicines. Although G. uralensis has been shown to affect the expression and activity of the key metabolic enzyme cytochrome P450 (CYP450), the detailed mechanism of this process has yet to be elucidated. The present study aimed to elucidate the effects of bioactive components of G. uralensis on different isoforms of CYP450 and determine the ability of these components to modulate drug properties. In the present study, mRNA levels of CYP1A2, CYP2D6, CYP2E1, and CYP3A4 were investigated by quantitative polymerase chain reaction (qPCR) in HepG2 cells following treatment with the major bioactive compounds of G. uralensis. The activity of CYP450 enzymes was investigated in human liver microsomes using the cocktail probe drug method, and the metabolites of specific probes were detected by UPLC‑MS/MS. The effects of G. uralensis on CYP450 were assessed using bioinformatics network analysis. Several compounds from G. uralensis had various effects on the expression and activity of multiple CYP450 isoforms. The majority of the compounds analysed the inhibited expression of CYP2D6 and CYP3A4. Several CYP isoforms were differentially modulated depending on the specific compound and dose tested. In conclusion, the present study suggested that G. uralensis influenced the expression and activity of CYP450 enzymes. Therefore, caution should be taken when G. uralensis is co‑administered with drugs that are known to be metabolized by CYP450. This study contributed to the knowledge of the mechanisms by which this medicinal plant, commonly known as licorice, modulates drug efficacy.