Pouyfung Phisit, Sarapusit Songklod, Rongnoparut Pornpimol
Department of Biochemistry, Faculty of Science, Mahidol University, 272 Rama 6 Rd, Ratchathewi, Bangkok, 10400, Thailand.
Department of Biochemistry and Center for Innovation in Chemistry, Faculty of Science, Burapha University, 169 Long-Hard Bangsaen Rd, Muang, Chonburi, 20131, Thailand.
Phytother Res. 2017 Dec;31(12):1916-1925. doi: 10.1002/ptr.5939. Epub 2017 Oct 10.
Vernonia cinerea has been widely used in traditional medicines for various diseases and shown to aid in smoking abstinence and has anticancer properties. V. cinerea bioactive compounds, including flavonoids and hirsutinolide-type sesquiterpene lactones, have shown an inhibition effect on the nicotine-metabolizing cytochrome P450 2A6 (CYP2A6) enzyme and hirsutinolides reported suppressing cancer growth. In this study, V. cinerea ethanol extract and its bioactive compounds, including four flavonoids and four hirsutinolides, were investigated for an inhibitory effect on human liver microsomal CYPs 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4 using cocktail inhibition assays combined with LC-MS/MS analysis. Among tested flavonoids, chrysoeriol was more potent in inhibition on CYP2A6 and CYP1A2 than other liver CYPs, with better binding efficiency toward CYP2A6 than CYP1A2 (K values in competitive mode of 1.93 ± 0.05 versus 3.39 ± 0.21 μM, respectively). Hirsutinolides were prominent inhibitors of CYP2A6 and CYP2D6, with IC values of 12-23 and 15-41 μM, respectively. These hirsutinolides demonstrated time-dependent inhibition, an indication of mechanism-based inactivation, toward CYP2A6. Quantitative prediction of microsomal metabolism of these flavonoids and hirsutinolides, including half-lives and hepatic clearance rate, was examined. These findings may have implications for further in vivo studies of V. cinerea. Copyright © 2017 John Wiley & Sons, Ltd.
裸柱菊已被广泛用于治疗各种疾病的传统药物中，具有辅助戒烟和抗癌特性。裸柱菊的生物活性化合物，包括黄酮类化合物和绒毛内酯型倍半萜内酯，已显示出对尼古丁代谢细胞色素P450 2A6（CYP2A6）酶的抑制作用，并且有报道称绒毛内酯可抑制癌症生长。在本研究中，使用鸡尾酒抑制试验结合液相色谱-串联质谱分析，研究了裸柱菊乙醇提取物及其生物活性化合物（包括四种黄酮类化合物和四种绒毛内酯）对人肝微粒体细胞色素P450 1A2、2A6、2B6、2C8、2C9、2C19、2D6、2E1和3A4的抑制作用。在所测试的黄酮类化合物中，芹菜素对CYP2A6和CYP1A2的抑制作用比其他肝细胞色素P450更强，对CYP2A6的结合效率比对CYP1A2更好（竞争模式下的K值分别为1.93±0.05和3.39±0.21μM）。绒毛内酯是CYP2A6和CYP2D6的显著抑制剂，IC值分别为12 - 23和15 - 41μM。这些绒毛内酯对CYP2A6表现出时间依赖性抑制，这是基于机制失活的一种表现。研究了这些黄酮类化合物和绒毛内酯微粒体代谢的定量预测，包括半衰期和肝清除率。这些发现可能对裸柱菊的进一步体内研究有启示意义。版权所有© 2017约翰威立父子有限公司。
