6',7'-dihydroxybergamottin의 항염증 및 주름개선 효과

Abstract

In this study, in order to investigate the anti-inflammatory and anti-aging effects of 6',7'-dihydroxybergamottin (DHB). First, this study was designed to elucidate the pharmacological and biological effects of DHB on the production of pro-inflammatory 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 E_2 (PGE_2) production in RAW 264.7 cells. The inhibitory effects of DHB included dose-dependent decreases in the expression of inducible NOS (iNOS) and cyclooxygenase-2 (COX-2) proteins. DHB effectively inhibited LPS-induced production of pro-inflammatory cytokines (tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)) in a concentration-dependent manner. Furthermore, DHB inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) (extracellular signal–regulated kinases (ERK) and c-Jun N-terminal kinases(JNK)) in LPS-induced RAW 264.7 cells. These results suggest that DHB attenuated LPS-induced release of pro-inflammatory mediators and cytokines probably via suppressing the activation of MAPK signaling. we also investigated the possibility that DHB may be an effective anti-wrinkle agent. up to 200 µM DHB was shown to be non-toxic to human dermal fibroblasts (HDF). Then, a human type I pro-collagen production assay was performed in HDF cells treated with DHB. The results showed that DHB significantly increased type I pro-collagen production. DHB was also found to induce the phosphorylation of Smad2, an important transcription factor involved in the production of type I procollagen. In addition, DHB strongly inhibited MMP-1 production in a concentration-dependent manner. DHB inhibited the phosphorylation of MAPKs (ERK and JNK) in TNF-α induced Human Dermal Fibroblast cells. These results suggest that DHB attenuated TNF-α induced release of MMP-1 probably via suppressing the activation of MAPK signaling. lastly, To assess the suitability of DHB for cosmetic applications, we also performed MTT assays on HaCaT human keratinocytes. DHB did not display any cytotoxicity in these assays. From these results suggest that DHB may be potential anti-wrinkle and anti- inflammatory agent for topical application in the cosmetic industry.