Kim Jang Hoon, Huh Yun-Chan, Hur Mok, Park Woo Tae, Moon Youn-Ho, Kim Tae Il, Kim Seon Mi, Koo Sung-Cheol
Department of Herbal Crop Research, National Institute of Horticultural & Herbal Science, RDA, Eumsung, Chungbuk, 27709, Korea.
Heliyon. 2023 Sep 14;9(9):e19772. doi: 10.1016/j.heliyon.2023.e19772. eCollection 2023 Sep.
Soluble epoxide hydrolase (sEH) is a therapeutic target for inflammation. In the present study, we isolated one new () and four known (-) compounds from the ethyl acetate fraction of hemp seed hulls. Their structures were elucidated as lignanamides via nuclear magnetic resonance and mass spectral analyses. All five compounds inhibited sEH activity, with half-maximal inhibitory concentrations of 2.7 ± 0.3 to 18.3 ± 1.0 μM. These lignanamides showed a competitive mechanism of inhibition via binding to sEH, with values below 10 μmol. Molecular simulations revealed that compounds - fit stably into the active site of sEH, and the key amino acid residues participating in their bonds were identified. It was confirmed that the potential inhibitors and continuously maintained a distance of 3.5 Å from one (Tyr383) and four amino (Asp335, Tyr383, Asn472, tyr516) residues, respectively. These findings provide a framework for the development of naturally derived sEH inhibitors.
可溶性环氧化物水解酶（sEH）是炎症治疗的一个靶点。在本研究中，我们从麻籽壳的乙酸乙酯部分分离出一种新的（）化合物和四种已知的（-）化合物。通过核磁共振和质谱分析确定它们的结构为木脂酰胺。所有五种化合物均抑制sEH活性，半数最大抑制浓度为2.7±0.3至18.3±1.0μM。这些木脂酰胺通过与sEH结合表现出竞争性抑制机制，解离常数低于10μmol。分子模拟表明，化合物-稳定地契合到sEH的活性位点，并确定了参与它们结合的关键氨基酸残基。证实潜在抑制剂和分别与一个（Tyr383）和四个氨基酸（Asp335、Tyr383、Asn472、tyr516）残基持续保持3.5Å的距离。这些发现为天然来源的sEH抑制剂的开发提供了一个框架。
