Department of Biology Education, Teachers College and Institute for Phylogenomics and Evolution, Kyungpook National University, Daegu 41566, Republic of Korea.
Institute of Marine Biochemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay, Hanoi 10072, Vietnam.
Mar Drugs. 2024 Aug 17;22(8):373. doi: 10.3390/md22080373.
Soluble epoxide hydrolase (sEH) is essential for converting epoxy fatty acids, such as epoxyeicosatrienoic acids (EETs), into their dihydroxy forms. EETs play a crucial role in regulating blood pressure, mediating anti-inflammatory responses, and modulating pain, making sEH a key target for therapeutic interventions. Current research is increasingly focused on identifying sEH inhibitors from natural sources, particularly marine environments, which are rich in bioactive compounds due to their unique metabolic adaptations. In this study, the sEH inhibitory activities of ten cembranoid diterpenes (-) isolated from the soft coral were evaluated. Among them, compounds and exhibited considerable sEH inhibition, with IC values of 70.68 μM and 78.83 μM, respectively. Enzyme kinetics analysis revealed that these two active compounds inhibit sEH through a non-competitive mode. Additionally, in silico approaches, including molecular docking and molecular dynamics simulations, confirmed their stability and interactions with sEH, highlighting their potential as natural therapeutic agents for managing cardiovascular and inflammatory diseases.
可溶性环氧化物水解酶 (sEH) 对于将环氧脂肪酸（如环氧二十碳三烯酸 (EETs)）转化为其二羟基形式至关重要。EETs 在调节血压、介导抗炎反应和调节疼痛方面发挥着关键作用，因此 sEH 成为治疗干预的关键靶点。目前的研究越来越关注从天然来源，特别是海洋环境中，寻找 sEH 抑制剂，因为海洋环境由于其独特的代谢适应而富含生物活性化合物。在这项研究中，评估了从软珊瑚中分离得到的 10 种海鞘素二萜 (-) 的 sEH 抑制活性。其中，化合物 和 表现出相当强的 sEH 抑制作用，IC 值分别为 70.68 μM 和 78.83 μM。酶动力学分析表明，这两种活性化合物通过非竞争性模式抑制 sEH。此外，包括分子对接和分子动力学模拟在内的计算方法证实了它们与 sEH 的稳定性和相互作用，强调了它们作为治疗心血管和炎症性疾病的天然治疗剂的潜力。
