Inhibition of soluble epoxide hydrolase by steroidal metabolites from the starfish Patiria pectinifera: Integrated enzyme kinetic and computational studies.

Authors

Nguyen Viet Phong, Le Ba Vinh, Hoang Le Tuan Anh, Sung Don Lim, Seo Young Yang

Published in

Steroids. Pages 109854. Sep 11, 2026. Epub Sep 11, 2026.

Abstract

Soluble epoxide hydrolase (sEH) is a promising therapeutic target for inflammation-related disorders; however, current synthetic inhibitors are limited due to pharmacokinetic constraints. Marine steroidal metabolites offer a potential source of natural sEH inhibitors. Therefore, this study aims to investigate the sEH inhibitory activity of compounds isolated from the starfish Patiria pectinifera. Six steroidal compounds (1-6) were isolated and evaluated using enzymatic assays, kinetic analysis, molecular docking, and molecular dynamics simulations. Compounds 1 and 2 demonstrated potent sEH inhibition (IC₅₀ = 16.10 ± 2.43 μM and 4.13 ± 1.24 μM, respectively), while compounds 3-6 were inactive. Kinetic studies showed mixed-type inhibition, with lower K_is than K_i values, indicating preferential binding to the enzyme-substrate complex. Computational analyses revealed that compounds 1 and 2 bind to distinct sites within the C-terminal domain with higher affinity than that of the native substrate, inducing conformational changes consistent with allosteric modulation. These findings indicate compounds 1 and 2 as promising allosteric sEH inhibitors, highlighting the potential of P. pectinifera steroids as anti-inflammatory agents.

PMID:
42727905
Bibliographic data and abstract were imported from PubMed on 12 Sep 2026.

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