title: 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.
authors.affiliation: Department of Pharmacy, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.affiliation: Center Laboratory, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, P.R. China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Center Laboratory, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, P.R. China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Center Laboratory, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, P.R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: Rui
authors.affiliation: Center Laboratory, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, P.R. China.
authors.forename: Zhongfeng
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, P.R. China.
authors.forename: Lirong
authors.initials: L
authors.lastname: Wu
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics / Q000378:metabolism; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D029882:Glycyrrhiza uralensis / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D028321:Plant Preparations / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D053719:Tandem Mass Spectrometry
chemical_list: D028321:Plant Preparations; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human