Phytochemical constituents from Scutellaria baicalensis in soluble epoxide hydrolase inhibition: Kinetics and interaction mechanism merged with simulations

In our search for soluble epoxide hydrolase (sEH) inhibitors from plants, we found that water extracts of Scutellaria baicalensis Georgi displayed significant inhibitory activity against sEH in vitro. Extracts of S. baicalensis were separated, resulting in the isolation of thirty compounds (1-30), including six lignin (1-6), sixteen flavones (7-22), and five amides (23-27). Their structures were determined on the basis of H-1 and C-13 NMR and MS spectra. Compounds 1-6 were first reported in the genus Scutellaria. All the isolated compounds were assayed for their inhibitory activities against sEH. Compounds 25-27 showed significant inhibitory activities against sEH with IC50 values of 6.06 +/- 0.12, 7.83 +/- 0.52, and 632 +/- 0.31 mu M, respectively, and compounds 3-6,12,18, and 22 displayed moderate inhibitory activities against sEH with IC50 values from 20.82 +/- 0.78 mu M to 56.61 +/- 0.98 mu M. The inhibition kinetic analysis results indicated that compounds 25-27 were all uncompetitive. Molecular docking studies were performed to get insights into inhibition mechanisms of compounds 25-27 against sEH. (C) 2019 Published by Elsevier B.V.