Isocucurbic Acid Derivatives and Soluble Epoxide Hydroxylase Inhibitors from the Flowers of Chrysanthemum indicum L.

Soluble epoxide hydrolase (sEH) inhibitory activity guided fractionation and isolation of two new isocucurbic acid derivatives (1 and 2) and nine known compounds (3-11) from the flowers of Chrysanthemum indicum L. Their structures were elucidated on the basis of spectroscopic data interpretation and comparison with those reported in previous studies. Luteolin (3), acacetin-7-O-beta-D-glucopyranoside (6), and methyl 3,4-di-O-caffeoylquinate (10) displayed sEH inhibitory activities with IC50 values ranging from 13.7. 3.6 to 20.8. 0.4 mu M. Enzyme kinetic analysis revealed that 3, 6, and 10 were non-competitive inhibitors with K-i values of 14.8 +/- 0.5, 31 +/- 2. 0.8, and 3.9 +/- 0.2 mu M, respectively. Additionally, molecular docking studies indicated compound 10 had the ability to form six hydrogen bonds at sEH active site, resulting binding energy as low as 9.58 Kcal/mol.