Harnessing Traditional Medicine for Modern Inflammation Targets: Computational Discovery of Oldenlandia diffusa as a Source of Predicted sEH Inhibitors With Validated Anti-Inflammatory Effects in Vitro

[摘要] ObjectiveChronic inflammation is a pathological basis for numerous diseases, and soluble epoxide hydrolase (sEH) has emerged as a promising target for anti-inflammatory intervention. This study aimed to identify potential sEH inhibitors derived from the traditional Chinese medicinal herb Oldenlandia diffusa through integrated computational and experimental methodologies.MethodsA pharmacophore model was constructed from 41 known sEH inhibitors and utilized to virtually screen 948 metabolites of Oldenlandia diffusa. The identified hits underwent molecular docking, ADMET prediction, induced-fit docking, and 50 ns molecular dynamics simulation. The anti-inflammatory activity of the selected compounds was assessed in LPS-stimulated RAW264.7 macrophages by measuring levels of NO and TNF-α.ResultsTwo compounds, Syringaresinol and 3,7-Di-O-methylquercetin, exhibited favorable ADMET profiles, low cytotoxicity, and stable binding to sEH during molecular dynamics simulation (equilibrated RMSD ∼0.8 nm with fluctuations <0.1 nm; MM-PBSA free energies: –117.49±14.01 and –71.47±13.87 kJ/mol). Both compounds reduced NO and TNF-α levels in a dose-dependent manner in LPS-induced RAW264.7 macrophages. These findings identify metabolites of Oldenlandia diffusa as computationally predicted sEH inhibitors with confirmed anti-inflammatory activity, warranting further direct enzymatic validation.ConclusionSyringaresinol and 3,7-Di-O-methylquercetin from Oldenlandia diffusa are predicted sEH inhibitors with validated anti-inflammatory effects, supporting their further exploration as natural leads for therapeutic applications in inflammation.

[发布日期] 2026-08-01

[关键词] Oldenlandia diffusa;anti-inflammatory;virtual screening;pharmacophore;induced-fit docking;molecular dynamics simulation