Natural soluble epoxide hydrolase inhibitors from Inula helenium and their interactions with soluble epoxide hydrolase

The inhibition of soluble epoxide hydrolase (sEH) is regarded as a promising therapeutic approach to treat in-flammation and its related disorders. In present work, we investigated inhibitory effects of forty-nine kinds of tra-ditional Chinese medicines against sEH. Inula helenium showed significant inhibitory effect against sEH, and the extract of I. helenium was isolated to obtain eight compounds, including 4H-tomentosin (1), xanthalongin (2), linoleic acid (3), 8-hydroxy-9-isobutyryloxy-10(2)-methylbutyrylthymol (4), dehydrocostus lactone (5), alantolactone (6), costunolide (7), and isoalantolactone (8). Among them, 4H-tomentosin (1), xanthalongin (2), and linoleic acid (3) showed significantly inhibitory activities on sEH with half maximal inhibitory concen-tration (IC50) from 5.88 +/- 0.97 mu M to 11.63 +/- 0.58 mu M. The inhibition kinetics suggested that 4H-tomentosin (1) and xanthalongin (2) were mixed-competitive type inhibitors with inhibition constants (K-i) of 7.02 and 6.57 mu M, respectively, and linoleic acid (3) was a competitive type inhibitor with a K-i values of 3.52 mu M. The po-tential interactions of 4H-tomentosin (1), xanthalongin (2), and linoleic acid (3) with sEH were analyzed by mo-lecular docking, which indicated that these bioactive compounds had interactions with key amino acid residues Tyr343, Ile363, Tyr383, and His524. (C) 2020 Elsevier B.V. All rights reserved.