详情页 - 广东省中医院知识库

当前位置：首页 > 详情页

Cytochrome P450 3A4 suppression by epimedium and active compound kaempferol leads to synergistic anti-inflammatory effect with corticosteroid

文献详情

资源类型：

Pubmed体系：

作者：

机构： [1]Guangdong Hospital of Integrated Traditional Chinese and Western Medicine, Guangzhou University of Chinese Medicine, Foshan, China. [2]Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY, United States. [3]Central Laboratory, Affiliated Hospital, Changchun University of Chinese Medicine, Changchun, China. [4]Academy of Chinese Medical Science, Henan University of Chinese Medicine, Zhengzhou, China. [5]Department of Pharmacology, New York Medical College, Valhalla, NY, United States. [6]General Nutraceutical Technology, Elmsford, NY, United States. [7]Department of Pediatrics, Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, United States. [8]Guangzhou ImVin Pharmaceutical Co., Ltd., Guangzhou, China. [9]Department of Pharmacology, School of Medicine, Yale University, New Haven, China. [10]Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China. [11]Department of Otolaryngology, Westchester Medical Center New York Medical College, Valhalla, NY, United States.

出处：

DOI：

ISSN：

摘要：

Introduction: Cytochrome P450 (CYP) 3A4 is a major drug metabolizing enzyme for corticosteroids (CS). Epimedium has been used for asthma and variety of inflammatory conditions with or without CS. It is unknown whether epimedium has an effect on CYP 3A4 and how it interacts with CS. We sought to determine the effects of epimedium on CYP3A4 and whether it affects the anti-inflammatory function of CS and identify the active compound responsible for this effect. Methods: The effect of epimedium on CYP3A4 activity was evaluated using the Vivid CYP high-throughput screening kit. CYP3A4 mRNA expression was determined in human hepatocyte carcinoma (HepG2) cells with or without epimedium, dexamethasone, rifampin, and ketoconazole. TNF-α levels were determined following co-culture of epimedium with dexamethasone in a murine macrophage cell line (Raw 264.7). Active compound (s) derived from epimedium were tested on IL-8 and TNF-α production with or without corticosteroid, on CYP3A4 function and binding affinity. Results: Epimedium inhibited CYP3A4 activity in a dose-dependent manner. Dexamethasone enhanced the expression of CYP3A4 mRNA, while epimedium inhibited the expression of CYP3A4 mRNA and further suppressed dexamethasone enhancement of CYP3A4 mRNA expression in HepG2 cells (p < 0.05). Epimedium and dexamethasone synergistically suppressed TNF-α production by RAW cells (p < 0.001). Eleven epimedium compounds were screened by TCMSP. Among the compounds identified and tested only kaempferol significantly inhibited IL-8 production in a dose dependent manner without any cell cytotoxicity (p < 0.01). Kaempferol in combination with dexamethasone showed complete elimination of TNF-α production (p < 0.001). Furthermore, kaempferol showed a dose dependent inhibition of CYP3A4 activity. Computer docking analysis showed that kaempferol significantly inhibited the catalytic activity of CYP3A4 with a binding affinity of -44.73kJ/mol. Discussion: Inhibition of CYP3A4 function by epimedium and its active compound kaempferol leads to enhancement of CS anti-inflammatory effect.Copyright © 2023 Li, Yu, Maskey, Musa, Wang, Garcia, Guo, Yang, Srivastava, Dunkin, Li, Guo, Cheng, Yuan, Tiwari and Li.

基金：

语种：

PubmedID：

中科院(CAS)分区：

出版当年[2021]版：

大类 | 2 区

医学

小类 | 2 区药学

最新[2025]版：

大类 | 3 区医学

小类 | 3 区药学

第一作者：

第一作者机构： [1]Guangdong Hospital of Integrated Traditional Chinese and Western Medicine, Guangzhou University of Chinese Medicine, Foshan, China. [2]Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY, United States.

共同第一作者：

通讯作者：

通讯机构： [2]Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY, United States. [11]Department of Otolaryngology, Westchester Medical Center New York Medical College, Valhalla, NY, United States.

推荐引用方式(GB/T 7714)：

APA：

MLA：