Anti-inflammatory Effect of 6’,7’-Dihydroxybergamottin on Lipopolysaccharide-stimulated RAW 264.7 Ma
6’,7’-Dihydroxybergamottin (DHB) and its metabolites are natural furanocoumarins foundprincipally in grapefruit juice. They have been shown to exert inhibitory effects on cytochrome P450.However, it is unknown whether DHB modulates inflammatory responses in RAW 264.7 macrophagecells. The present study was therefore designed to elucidate the pharmacological and biological effects ofDHB on the production of proinflammatory cytokines and inflammatory mediators by macrophages. Theresults obtained from the study indicate that DHB is an effective inhibitor of lipopolysaccharide (LPS)-inducednitric oxide (NO) and prostaglandin (PG) E2 production in RAW 264.7 cells. The inhibitory effectsof DHB included dose-dependent decreases in the expression of inducible NO synthase and cyclooxygenase-2 proteins. DHB effectively inhibited LPS-induced production of proinflammatory cytokines (tumornecrosis factor alpha and interleukin 6) in a concentration-dependent manner. Furthermore, DHB inhibitedthe phosphorylation of mitogen-activated protein kinases (MAPKs) (ERK1/2 and JNK) in LPS-stimulatedRAW 264.7 cells. These results suggest that DHB attenuated LPS-induced release of proinflammatorymediators and cytokines probably via suppressing the activation of MAPK signaling. To assess the suitabilityof DHB for cosmetic applications, we also performed MTT assays on HaCaT keratinocytes. DHBdid not display any cytotoxicity in these assays. From these results, we suggest that DHB may be considereda potential antiinflammatory candidate.
