광귤나무(Citrus aurantium) 열매에서 분리된 쿠마린의 iNOS 억제효과

Inhibitory effects of coumarins from the fruit of Citrus aurantium against iNOS activity

Citrus fruits have been used as an edible fruit, and also as a traditional medicine, since ancient times. A crude methanol extract of Citrus aurantium was shown to suppress inducible proinflammatory cytokines, but its constituents were not 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. The structures of these compounds were elucidated by extensive application of spectroscopic techniques, including 2D NMR spectroscopy and mass spectrometry. All of the isolated compounds were evaluated for their ability to inhibit the production of proinflammatory cytokine inducible nitric oxide synthase (iNOS) in lipopolysaccharide-activated RAW264.7 cells. Compounds 2−5 significantly suppressed iNOS production but compound 1 had no iNOS inhibitory effects. These results indicate that at least three furanocoumarins and one 7-geranyloxycoumarin are involved in the suppressive effects of citrus fruits against the production of inducible inflammatory cytokines.