Protostane-type triterpenoids as natural soluble epoxide hydrolase inhibitors: Inhibition potentials and molecular dynamics.

The inhibition of soluble epoxide hydrolase (sEH) is a promising therapeutic approach to treat inflammation and other disorders. In our present investigation on searching for sEH inhibitors from traditional Chinese medicines, we found that Alisma orientale displayed inhibition of sEH. We constructed a small library of protostane-type triterpenoids (1-25) isolated from A. orientale, and screened their inhibitory activities. Alismanin B (1), 11-deoxy-25-anhydro alisol E (4), 11-deoxy alisol B (5), and 25-O-ethyl alisol A (15) displayed concentration-dependently inhibitory activities against sEH with IC50 values from 3.40 ± 0.57 µM to 9.57 ± 0.88 µM. 11-Deoxy-25-anhydro alisol E (4) and 11-deoxy alisol B (5) were defined as mixed-type competitive inhibitors with Ki values of 12.6 and 3.48 µM, respectively, based on the result of inhibition kinetics. The potential interaction mechanism of 11-deoxy alisol B (5) with sEH was analyzed by molecular docking and molecular dynamics, revealing that amino acid residues Trp336 and Tyr466 were vital for its inhibitory activity.

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. baicalensiswere separated, resulting in the isolation of thirty compounds (1-30), including six lignins (1-6), sixteen flavones (7-22), and five amides (23-27). Their structures were determined on the basis of1H and13C 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 ±â€¯0.12, 7.83 ±â€¯0.52, and 6.32 ±â€¯0.31 µM, respectively, and compounds 3-6, 12, 18, and 22 displayed moderate inhibitory activities against sEH with IC50 values from 20.82 ±â€¯0.78 µM to 56.61 ±â€¯0.98 µM. 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.