Inhibitory Activity of Natural cis -Khellactone on Soluble Epoxide Hydrolase and Proinflammatory Cytokine Production in Lipopolysaccharides-Stimulated RAW264.7 Cells.

The pursuit of anti-inflammatory agents has led to intensive research on the inhibition of soluble epoxide hydrolase (sEH) and cytokine production using medicinal plants. In this study, we evaluated the efficacy of cis -khellactone, a compound isolated for the first time from the roots of Peucedanum japonicum . The compound was found to be a competitive inhibitor of sEH, exhibiting an IC 50 value of 3.1 ± 2.5 µM and k i value of 3.5 µM. Molecular docking and dynamics simulations illustrated the binding pose of (-) cis -khellactone within the active site of sEH. The results suggest that binding of the inhibitor to the enzyme is largely dependent on the Trp336-Gln384 loop within the active site. Further, cis -khellactone was found to inhibit pro-inflammatory cytokines, including NO, iNOS, IL-1β, and IL-4. These findings affirm that cis -khellactone could serve as a natural therapeutic candidate for the treatment of inflammation.