광귤나무(Citrus aurantium) 열매에서 분리된 쿠마린의 iNOS 억제효과

Abstract

Citrus fruits have been used as an edible fruit, and also as a traditional medicine, since ancient times. A crudemethanol extract of Citrus aurantium was shown to suppress inducible proinflammatory cytokines, but its constituents werenot known. In this study, we isolated four furanocoumarins, bergapten (1), imperatorin (2), isoimperatorin(3), and phellopterin(4), and one 7-geranyloxycoumarin, auraptene (5), from a methanol extract of dried Citrus aurantium fruit. Thestructures of these compounds were elucidated by extensive application of spectroscopic techniques, including 2D NMRspectroscopy and mass spectrometry. All of the isolated compounds were evaluated for their ability to inhibit the productionof proinflammatory cytokine inducible nitric oxide synthase (iNOS) in lipopolysaccharide-activated RAW264.7 cells. Compounds2−5 significantly suppressed iNOS production but compound 1 had no iNOS inhibitory effects. These results indicatethat at least three furanocoumarins and one 7-geranyloxycoumarin are involved in the suppressive effects of citrus fruitsagainst the production of inducible inflammatory cytokines.