In vitro and in silico investigation of anthocyanin derivatives as soluble epoxide hydrolase inhibitors

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 IC50 values ranging from 4.3 +/- 0.2 to 25.3 +/- 2.6 mu M. 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 10 ns. 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. (C) 2018 Published by Elsevier B.V.