Shon Jong Cheol, Phuc Nguyen Minh, Kim Won Cheol, Heo Jae Kyung, Wu Zhexue, Lee Hyunyoung, Liu Kwang-Hyeon
BK21 Plus KNU Multi-Omics based Creative Drug Research Team, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, 41566, South Korea.
Saokim Pharmaceutical Company, Hanoi, Vietnam.
Biopharm Drug Dispos. 2017 Dec;38(9):553-556. doi: 10.1002/bdd.2101. Epub 2017 Nov 6.
Acetylshikonin is a biologically active compound with anti-cancer and anti-inflammatory activity, which is isolated from the roots of Lithospermum erythrorhizoma. An inhibitory effect of acetylshikonin against CYP2J2 activity was discovered recently. Based on this result, this study was expanded to evaluate the inhibitory effects of acetylshikonin against nine different cytochrome P450 (P450) isoforms in human liver microsomes (HLMs) using substrate cocktails incubation assay. Acetylshikonin showed a strong inhibitory effect against all P450s tested with IC values of 1.4-4.0 μ m. Pre-incubation of acetylshikonin with HLMs and NADPH did not alter the inhibition potency, indicating that acetylshikonin is not a mechanism-based inhibitor. SKF-525A, a widely used non-specific P450 inhibitor, had no inhibitory activity against CYP1A2, 2A6, 2E1 and 2J2, while it showed an inhibitory effect against CYP2B6, CYP2C19 and 2D6 with IC values of 2.5, 3.6 and 0.5 μ m, respectively. Our findings indicate that acetylshikonin may be a novel general P450 inhibitor, which could replace SKF-525A.
乙酰紫草素是一种具有抗癌和抗炎活性的生物活性化合物，它是从紫草的根部分离出来的。最近发现乙酰紫草素对CYP2J2活性有抑制作用。基于这一结果，本研究进行了扩展，采用底物鸡尾酒孵育试验评估乙酰紫草素对人肝微粒体（HLMs）中九种不同细胞色素P450（P450）同工酶的抑制作用。乙酰紫草素对所有测试的P450均表现出强烈的抑制作用，IC值为1.4 - 4.0 μ m。乙酰紫草素与HLMs和NADPH预孵育不会改变抑制效力，表明乙酰紫草素不是基于机制的抑制剂。SKF - 525A是一种广泛使用的非特异性P450抑制剂，对CYP1A2、2A6、2E1和2J2没有抑制活性，而对CYP2B6、CYP2C19和2D6有抑制作用，IC值分别为2.5、3.6和0.5 μ m。我们的研究结果表明，乙酰紫草素可能是一种新型的通用P450抑制剂，可以替代SKF - 525A。
