Evaluation potential effects of Picroside II on cytochrome P450 enzymes in vitro and in vivo.

Autor: Zhou N; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221004, China; School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 210009, Jiangsu, China., Zhu Y; School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China., Hu M; School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China., Zheng R; School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China., Sun M; School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 210009, Jiangsu, China., Bian Y; School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 210009, Jiangsu, China., Chen X; School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 210009, Jiangsu, China. Electronic address: chenxj-lab@hotmail.com., Li T; School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, Jiangsu, China. Electronic address: dreamerltt@163.com.
Jazyk: angličtina
Zdroj: Journal of ethnopharmacology [J Ethnopharmacol] 2023 Oct 05; Vol. 314, pp. 116582. Date of Electronic Publication: 2023 May 14.
DOI: 10.1016/j.jep.2023.116582
Abstrakt: Ethnopharmacology Relevance: Picrorhiza scrophulariiflora Pennell, a well-known Chinese herb, has been traditionally utilized as an antioxidant and anti-inflammatory agent. One of its main bioactive components is Picroside II, a glycoside derivative. However, there is limited information on the effects of Picroside II on the activity of cytochrome P450 (CYP) enzymes nor on potential herb-drug interactions are rarely studied.
Aim of the Study: The purpose of the study was to investigate the effects of Picroside II on the activity of cytochrome P450 enzymes in vitro and in vivo and its potential herb-drug interactions.
Materials and Methods: Specific probe substrates were employed to assess the effect of Picroside II on the activity of P450 enzymes. The inhibitory effects of Picroside II on CYP enzymes were assayed both in human (i.e., 1A, 2C9, 2C19, 2D6, 2E1, and 3A) and rat (i.e., 1A, 2C6/11, 2D1, 2E1, and 3A) liver microsomes in vitro. The inductive effects were investigated in rats following oral gavage of 2.5 mg/kg and 10 mg/kg Picroside II. A specific Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS) method was developed to determine the formation of specific metabolites.
Results: Enzyme inhibition results showed that Picroside II (0.5-200 μM) had no evident inhibitory effects on rat and human liver microsomes in vitro. Interestingly, the administration of multiple doses of 10 mg/kg Picroside II inhibited the activity of CYP2C6/11 by reducing the rate of formation of 4-hydroxydiclofenac and 4-hydroxymephenytoin, while Picroside II at 2.5 mg/kg increased the activity of CYP3A by promoting the formation of 1-hydroxymidazolam and 6-hydroxychlorzoxazone in rats. In addition, there were negligible effects on CYP1A, CYP2D1, and CYP2E1 in rats.
Conclusions: The results indicated that Picroside II modulated the activities of CYP enzymes and was involved in CYP2C and CYP3A medicated herb-drug interactions. Therefore, careful monitoring is necessary when Picroside II is used in combination with related conventional drugs.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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