Inhibitors of nitric oxide production from hops (Humulus lupulus L.)

Nitric oxide (NO) plays an important role in many inflammatory responses and is also involved in carcinogenesis. In the present study, we investigated the inhibitory effect of extracts from Humulus lupulus L. on both the production of NO and the expression of inducible NO synthase (iNOS) in mouse macrophage RAW 264.7 cells. The production of NO was induced by a combination of lipopolysaccharide (LPS) and IFN-gamma, and determined by Griess assay. The expression of iNOS was detected by Western blotting. The LPS/IFN-gamma-induced production of NO and expression of iNOS were significantly inhibited by the ethyl acetate soluble fraction of Humulus lupulus L. Through bioactivity guided fractionation, humulene, five chalcones, 2,2-di-(3-methyl-2-butyleyl)-4,5-dihydoxy-cyclopent-4-en-1,3-dione, lupulone and three of its derivatives were isolated from the ethyl acetate soluble fraction. The chalcones, including xanthohumol, significantly inhibited the production of NO by suppressing the expression of iNOS.