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

Overview

Journal Plants (Basel)

Date 2023 Oct 28

PMID 37896119

Authors

Jang Hoon Kim

Ji Hyeon Park

Sung Cheol Koo

Yun-Chan Huh

Mok Hur

Woo Tae Park

Youn-Ho Moon

Tae Il Kim

Byoung Ok Cho

Affiliations

Soon will be listed here.

Abstract

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 -khellactone, a compound isolated for the first time from the roots of . The compound was found to be a competitive inhibitor of sEH, exhibiting an IC value of 3.1 ± 2.5 µM and value of 3.5 µM. Molecular docking and dynamics simulations illustrated the binding pose of (-)-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, -khellactone was found to inhibit pro-inflammatory cytokines, including NO, iNOS, IL-1β, and IL-4. These findings affirm that -khellactone could serve as a natural therapeutic candidate for the treatment of inflammation.

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