Tianjin State Key Laboratory of Modern Chinese Medicine and School of Chinese, Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshanxi, Road, Nankai District, Tianjin, China; School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
College of Pharmacy, College (Institute) of Integrative Medicine, The National & Local Joint Engineering Research Center for Drug Development of Neurodegenerative Disease, Dalian Medical University, Dalian, China.
Int J Biol Macromol. 2019 Jul 15;133:1187-1193. doi: 10.1016/j.ijbiomac.2019.04.055. Epub 2019 Apr 10.
In our search for soluble epoxide hydrolase (sEH) inhibitors from plants, we found that water extracts of Scutellaria baicalensis Georgi displayed significant inhibitory activity against sEH in vitro. Extracts of S. baicalensiswere separated, resulting in the isolation of thirty compounds (1-30), including six lignins (1-6), sixteen flavones (7-22), and five amides (23-27). Their structures were determined on the basis ofH andC NMR and MS spectra. Compounds 1-6 were first reported in the genus Scutellaria. All the isolated compounds were assayed for their inhibitory activities against sEH. Compounds 25-27 showed significant inhibitory activities against sEH with IC values of 6.06 ± 0.12, 7.83 ± 0.52, and 6.32 ± 0.31 μM, respectively, and compounds 3-6, 12, 18, and 22 displayed moderate inhibitory activities against sEH with IC values from 20.82 ± 0.78 μM to 56.61 ± 0.98 μM. The inhibition kinetic analysis results indicated that compounds 25-27 were all uncompetitive. Molecular docking studies were performed to get insights into inhibition mechanisms of compounds 25-27 against sEH.
在寻找植物来源的可溶性环氧化物水解酶（sEH）抑制剂的过程中，我们发现黄芩的水提取物在体外对 sEH 表现出显著的抑制活性。黄芩提取物经分离，得到 30 个化合物（1-30），包括 6 个木脂素（1-6）、16 个黄酮（7-22）和 5 个酰胺（23-27）。它们的结构是根据 1 H和 13 C NMR 和 MS 谱确定的。化合物 1-6 首次在黄芩属中报道。所有分离得到的化合物均进行了对 sEH 的抑制活性测定。化合物 25-27 对 sEH 表现出显著的抑制活性，IC 值分别为 6.06±0.12、7.83±0.52 和 6.32±0.31μM，化合物 3-6、12、18 和 22 对 sEH 表现出中等抑制活性，IC 值为 20.82±0.78μM 至 56.61±0.98μM。抑制动力学分析结果表明，化合物 25-27 均为非竞争性抑制剂。进行了分子对接研究，以深入了解化合物 25-27 对 sEH 的抑制机制。
