Department of Horticultural and Crop Environment, National Institute of Horticultural and Herbal Science, RDA, Wanju 55365, Korea.
Department of Herbal Crop Research, National Institute of Horticultural and Herbal Science, RDA, Eumseong 27709, Korea.
Molecules. 2020 Sep 22;25(18):4352. doi: 10.3390/molecules25184352.
Flavonoids and triterpenoids were revealed to be the potential inhibitors on soluble epoxide hydrolase (sEH). The aim of this study is to reveal sEH inhibitors from Fuji apples. A flavonoid and three triterpenoids derived from the fruit of were identified as quercetin-3--arabinoside (), ursolic acid (), corosolic acid (), and 2-oxopomolic acid (). They had half-maximal inhibitory concentration of the inhibitors (IC) values of 39.3 ± 3.4, 84.5 ± 9.5, 51.3 ± 4.9, and 11.4 ± 2.7 μM, respectively, on sEH. The inhibitors bound to allosteric sites of enzymes in mixed () and noncompetitive modes (-). Molecular simulations were carried out for inhibitors and to calculate the binding force of ligands to receptors. The inhibitors bound to the left () and right () pockets next to the enzyme's active site. Based on analyses of their molecular docking and dynamics, it was shown that inhibitors and can stably bind sEH at 1 bar and 300 K. Finally, inhibitors and are promising candidates for further studies using cell-based assays and in vivo cardiovascular tests.
类黄酮和三萜烯被发现是可溶性环氧化物水解酶 (sEH) 的潜在抑制剂。本研究旨在从富士苹果中发现 sEH 抑制剂。从 的果实中鉴定出一种黄酮类化合物和三种三萜烯，分别为槲皮素-3-O-阿拉伯糖苷 ()、熊果酸 ()、齐墩果酸 () 和 2-氧代齐墩果酸 ()。它们对 sEH 的半最大抑制浓度（IC）值分别为 39.3 ± 3.4、84.5 ± 9.5、51.3 ± 4.9 和 11.4 ± 2.7 μM。抑制剂以混合 () 和非竞争性 (-) 模式结合到酶的变构部位。为了计算配体与受体的结合力，对抑制剂 和 进行了分子模拟。抑制剂结合在酶活性位点附近的左侧 () 和右侧 () 口袋中。基于对其分子对接和动力学的分析，表明抑制剂 和 可以在 1 bar 和 300 K 下稳定地与 sEH 结合。最后，抑制剂 和 是进一步使用基于细胞的测定和体内心血管测试的有前途的候选物。
