Wang Yiluan, Sun Jianliang, Chen Ling, Zhou Songyi, Lin Han, Wang Yiyan, Lin Nengming, Ge Ren-Shan
Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
Translational Medicine Research Center, Affiliated Hangzhou Hospital (Hangzhou First People's Hospital), Nanjing Medical University, No. 261 Huansha Road, Hangzhou, Zhejiang 310006, China.
Fitoterapia. 2017 Oct;122:61-66. doi: 10.1016/j.fitote.2017.08.005. Epub 2017 Aug 18.
Resveratrol, a common polyphenol, has extensive pharmacological activities. Resveratrol inhibits some steroid biosynthetic enzymes, indicating that it may block neurosteroid synthesis. The objective of the present study is to investigate the inhibition of resveratrol on neurosteroidogenic enzymes rat 5α-reductase 1 (SRD5A1), 3α-hydroxysteroid dehydrogenase (AKR1C9), and retinol dehydrogenase 2 (RDH2). The IC values of resveratrol on SRD5A1, AKR1C9, and RDH2 were >100μM, 0.436±0.070μM, and 4.889±0.062μM, respectively. Resveratrol competitively inhibited rat AKR1C9 and RDH2 against steroid substrates. Docking showed that resveratrol bound to the steroid binding pocket of AKR1C9. It exerted a mixed mode on these AKR1C9 and RDH2 against cofactors. In conclusion, resveratrol potently inhibited rat AKR1C9 and RDH2 to regulate local neurosteroid levels.
白藜芦醇是一种常见的多酚，具有广泛的药理活性。白藜芦醇可抑制某些类固醇生物合成酶，这表明它可能会阻断神经甾体的合成。本研究的目的是探究白藜芦醇对大鼠神经甾体生成酶5α-还原酶1（SRD5A1）、3α-羟基类固醇脱氢酶（AKR1C9）和视黄醇脱氢酶2（RDH2）的抑制作用。白藜芦醇对SRD5A1、AKR1C9和RDH2的半数抑制浓度（IC）值分别>100μM、0.436±0.070μM和4.889±0.062μM。白藜芦醇对大鼠AKR1C9和RDH2与类固醇底物存在竞争性抑制作用。分子对接显示白藜芦醇与AKR1C9的类固醇结合口袋相结合。它对这些AKR1C9和RDH2与辅因子发挥混合模式作用。总之，白藜芦醇可有效抑制大鼠AKR1C9和RDH2，从而调节局部神经甾体水平。
