Bioactive constituents isolated from the leaves of Phyllostachys Bambusoides with potent soluble epoxide hydrolase inhibitory activity: enzyme kinetics, molecular docking, and molecular dynamics simulations

초록

Traditional usage and in vitro studies have previously proven the effects of soluble epoxide hydrolase (sEH) inhibitors isolated from Phyllostachys bambusoides. A phytochemical investigation of Phyllostachys bambusoides led to the isolation of six known compounds: one phenolic amide moschamine (1), three flavonoids, including tricin (2), salcolin A (3), and luteolin 6-C-alpha-L-arabinopyranoside (4), as well as two neolignans (5-6). The structures of these compounds were determined spectroscopically; their nuclear magnetic resonance spectra were compared to reported spectra. The sEH inhibitory activity of all isolated compounds was examined. Compounds 1-4 exhibited strong sEH inhibitory activity with IC50 values of 30.6, 57.5, 16.8, and 11.7 mu M, respectively. Kinetic analyses of most potent compounds, 3 and 4, revealed that they were non-competitive inhibitors of sEH. The resulting molecular docking and molecular dynamics simulations have increased our understanding of the dynamic behavior of receptor-ligand binding between these compounds. Our findings suggest that flavonolignan and flavone derivatives from P. bambusoides leaves show promise as potential natural sEH inhibitors.

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