4-O-galloylalbiflorin inhibits the activity of CYP3A, 2C9, and 2D in human liver microsomes. (3rd August 2021)

• Record Type: Journal Article
• Authors: Sun, Yu; He, Mengya; Sun, Yanling; Wei, Jianhong
• Is Part Of: Xenobiotica. Volume 51:Number 8(2021)
• Page Start: 871
• Page End: 876
• Publication Date: 2021-08-03
• Subjects: 4-O-galloylalbiflorin -- Paeonia lactiflora Pall -- cytochrome P450 enzymes -- competitive inhibition -- non-competitive inhibition -- concentration-dependent inhibition -- time-dependent inhibition; Metabolism -- Periodicals; Drugs -- Physiological effect -- Periodicals; Food additives -- Periodicals; Chemicals -- Physiological effect -- Periodicals; Biochemistry -- Periodicals; Pharmaceutical Preparations -- metabolism -- Periodicals; Metabolism -- Periodicals; 574.133
• DOI: 10.1080/00498254.2021.1936688
• Languages: English
• ISSNs: 0049-8254

Abstract

Abstract: The effect of 4-O-galloylalbiflorin on the activity of cytochrome P450 enzymes (CYP450s) is an important factor that may induce drug-drug interaction. The effect of 4-O-galloylalbiflorin on the activity of CYP450s was evaluated in the presence of 0, 2.5, 5, 10, 25, 50, and 100 μM 4-O-galloylalbiflorin in pooled human liver microsomes. The inhibition model and corresponding parameters were assessed b fitting with Lineweaver-Burk plots. The time-dependent study was performed with the incubation time of 0, 5, 10, 15, and 30 min. 4-O-galloylalbiflorin significantly inhibited the activity of CYP3A, 2C9, and 2 D in a concentration-dependent manner with the IC50 values of 8.2, 13, and 11 μM, respectively. The inhibition of CYP3A was found to be non-competitive and time-dependent with the Ki value of 4.0 μM and the KI/Kinact value of 2.2/0.030 (μM·min). The inhibition of CYP2C9 and 2 D was not affected by the incubation time but was found to be competitive with the Ki values of 6.7 and 6.6 μM, respectively. The inhibitory effect of 4-O-galloylalbiflorin on the activity of CYP3A, 2C9, and 2 D implying the potential drug-drug interaction between 4-O-galloylalbiflorin and the drugs metabolized by these CYP450s.