Zhao_2021_Int.J.Biol.Macromol_183_811

Inhibition of soluble epoxide hydrolase (sEH) is considered to be an effective treatment for inflammation-related diseases, and small molecules origin from natural products show promising activity against sEH. Two undescribed protostanes, 3beta-hydroxy-25-anhydro-alisol F (1) and 3beta-hydroxy-alisol G (2) were isolated from Alisma orientale and identified as new sEH inhibitors with IC(50) values of 10.06 and 30.45 microM, respectively. Potential lead compound 1 was determined as an uncompetitive inhibitor against sEH, which had a K(i) value of 5.13 microM. In-depth molecular docking and molecular dynamics simulations revealed that amino acid residue Ser374 plays an important role in the inhibition of 1, which also provides an idea for the development of sEH inhibitors based on protostane-type triterpenoids.