Anti-inflammatory Effect of 6', 7'-Dihydroxybergamottin on Lipopolysaccharide-stimulated RAW 264.7 Macrophage Cells

6', 7'-Dihydroxybergamottin (DHB) and its metabolites are natural furanocoumarins found principally 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 macrophage cells. The present study was therefore designed to elucidate the pharmacological and biological effects of DHB on the production of proinflammatory cytokines and inflammatory mediators by macrophages. The results obtained from the study indicate that DHB is an effective inhibitor of lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin (PG) E-2 production in RAW 264.7 cells. The inhibitory effects of 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 (tumor necrosis factor alpha and interleukin 6) in a concentration-dependent manner. Furthermore, DHB inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) (ERK1/2 and JNK) in LPS-stimulated RAW 264.7 cells. These results suggest that DHB attenuated LPS-induced release of proinflammatory mediators and cytokines probably via suppressing the activation of MAPK signaling. To assess the suitability of DHB for cosmetic applications, we also performed MTT assays on HaCaT keratinocytes. DHB did not display any cytotoxicity in these assays. From these results, we suggest that DHB may be considered a potential antiinflammatory candidate.