Inhibitory Activity of Flavonoids, Chrysoeriol and Luteolin-7-O-Glucopyranoside, on Soluble Epoxide Hydrolase from Capsicum chinense

Three flavonoids derived from the leaves of Capsicum chinense Jacq. were identified as chrysoeriol (1), luteolin-7-O-glucopyranoside (2), and isorhamnetin-7-O-glucopyranoside (3). They had IC50 values of 11.6 +/- 2.9, 14.4 +/- 1.5, and 42.7 +/- 3.5 mu g/mL against soluble epoxide hydrolase (sEH), respectively. The three inhibitors (1-3) were found to non-competitively bind into the allosteric site of the enzyme with K-i values of 10.5 +/- 3.2, 11.9 +/- 2.8 and 38.0 +/- 4.1 mu g/mL, respectively. The potential inhibitors 1 and 2 were located at the left edge ofa U-tube shape that contained the enzyme active site. Additionally, we observed changes in several factors involved in the binding of these complexes under 300 K and 1 bar. Finally, it was confirmed that each inhibitor, 1 and 2, could be complexed with sEH by the induced fit and lock-and-key models.