Soluble epoxide hydrolase inhibitory activity by rhizomes of Kaempferia parviflora Wall. ex Baker

In our search for natural soluble epoxide hydrolase (sEH) inhibitors from plants, we found that the methanolic extract of the rhizomes of Kaempferia parviflora Wall. ex Baker (Zingiberaceae) significantly inhibits sEH in vitro. In a phytochemical investigation of dichloromethane fraction of K. parviflora rhizomes, we isolated sixteen compounds (1-16), including flavonoid derivatives (1-12), anthraquinones (13 and 14), triterpene (15), and triterpene glycoside (16). The structures of the isolated compounds were established in an extensive 1D and 2D NMR, as well as MS analysis. The sEH inhibitory activities of all isolated compounds were evaluated. Among the isolated flavonoid derivatives, 4, 6, 8, 10, and 12 were identified as potent inhibitors of sEH, with IC₅₀ values ranging from 0.9 ± 0.1 to 4.5 ± 0.1 μM. In addition, a kinetic analysis of the flavonoid derivatives (1-12) revealed that the inhibitory activity of flavonoid derivatives 1-4 and 6-12 is mixed with K_i values ranging from 0.1 ± 0.0 to 14.3 ± 0.3 μM, whereas compound 8 was a non-competitive with K_i = 0.3 ± 0.0 μM. These findings suggest that flavonoid derivatives from K. parviflora rhizomes are potential novel sEH inhibitors.