Soluble Epoxide Hydrolase Inhibitory and Anti-inflammatory Components from the Leaves of Eucommia ulmoides Oliver (Duzhong)

Eucommia ulmoides leaves have been used as a functional food and drink in China. The purpose of this study was to identify the bioactive constituents with soluble epoxide hydrolase (sEH) inhibitory activity and anti-inflammatory properties. Twenty-seven known compounds (127) were isolated from the leaves of E. ulmoides Oliver, and their structures were identified by NMR and ESIMS analysis; three of these, 2,5-dimethoxy-3-glucopyranosyl cinnamic alcohol (11), foliasalacioside E-2 (26), and icariside F-2 (27), were obtained from this plant for the first time. Compounds 1-7 exhibited soluble epoxide hydrolase (sEH) inhibitory activity at 100 mu M; among them, quercetin (1) and kaempferol (5) displayed potential activities with IC50 values of 22.5 +/- 0.9 and 31.3 +/- 2.6 mu M, respectively, with noncompetitive inhibition mode. Nuclear factor kappa B (NF-kappa B) inhibitory activity of the isolated compounds was evaluated by the NF-kappa B liciferase assay in HepG2 cells. Compounds 1, 9, 20, and 27 displayed potent NF-kappa B inhibitory effects, with IC50 values of 15.14 +/- 2.29, 15.23 +/- 2.34, 16.88 +/- 2.17, and 16.25 +/- 2.19 mu M, respectively, whereas other compounds showed weak inhibition of NF-kappa B transcriptional activity ranging from 17.54 to 92.6 mu M. A structure-activity relationship of flavonoids 1-9 was also discussed. The results obtained in this work might contribute to the understanding of pharmacological activities of E. ulmoides leaves and further investigation on its potential application values for food and drug.