Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeoungeup, Jeollabuk-do 56212, Republic of Korea.
Department of Horticultural and Crop Environment, National Institute of Horticultural and Herbal Science, RDA, Wanju 55365, Republic of Korea.
Int J Biol Macromol. 2018 Jun;112:961-967. doi: 10.1016/j.ijbiomac.2018.02.061. Epub 2018 Feb 12.
Anthocyanin derivatives are well-known secondary constituents contained in fruits. The inhibitory activity of anthocyanin derivatives toward soluble epoxide hydrolase (sEH) was tested for potential applications in the treatment of cardiovascular diseases. Anthocyanin derivatives 1-5 showed dose-dependent inhibitory activity toward sEH, with IC values ranging from 4.3±0.2 to 25.3±2.6μM. Lineweaver-Burk plots showed that all anthocyanin derivatives preferentially interacted with allosteric sites instead of active sites as noncompetitive (1-3) and mixed (4 and 5) inhibitors. Furthermore, the cavity located next to the active site may interact with anthocyanin derivatives (1-5) by molecular docking. Among the tested derivatives, (4) bonded with key amino acids at two loops around the binding site for 10ns. Finally, anthocyanin derivatives (1-5) are potential inhibitors of sEH, and anthocyanin-rich fruits may be useful for the targeted treatment of cardiovascular diseases via sEH inhibition.
花色苷衍生物是水果中含有的一类众所周知的次生成分。花色苷衍生物对可溶性环氧化物水解酶（sEH）的抑制活性被测试用于治疗心血管疾病的潜在应用。花色苷衍生物 1-5 对 sEH 表现出剂量依赖性抑制活性，IC 值范围为 4.3±0.2 至 25.3±2.6μM。Lineweaver-Burk 图表明，所有花色苷衍生物都优先与别构部位相互作用，而不是作为非竞争性（1-3）和混合（4 和 5）抑制剂与活性部位相互作用。此外，位于活性部位旁边的腔可能通过分子对接与花色苷衍生物（1-5）相互作用。在测试的衍生物中，（4）与结合位点周围两个环上的关键氨基酸结合长达 10ns。最后，花色苷衍生物（1-5）是 sEH 的潜在抑制剂，富含花色苷的水果可能通过抑制 sEH 用于心血管疾病的靶向治疗。
