6and#42892;,7and#42892;-Dihydroxybergamottin Promotes Collagen Synthesis by Activating the Smad Signaling Pathway in Human Dermal Fibroblasts

Skin wrinkling appears to be principally related to decrease levels of type I collagen, elastin, and hyaluronic acid, the principal components of the dermal layer of skin. The cause of wrinkling and the appearance of the skin resulting from decreased elasticity and skin sagging and pigmentation, is generally associated with decreased collagen and increased collagenase and Matrix Metalloproteinase (MMP) activities. In this study, we investigated the possibility that 6ꞌ,7ꞌ-Dihydroxybergamottin (DHB) may be an effective anti-wrinkle agent. DHB is a natural component of furanocoumarin which is frequently observed in citrus fruits. Initially, up to 200 μM DHB was shown to be non-toxic to human dermal fibroblasts. Then, a human type I pro-collagen production assay was performed in human dermal fibroblast cells treated with 50, 100, and 200 μM DHB. The results showed that DHB significantly increased type I pro-collagen production. In addition, DHB strongly inhibited MMP-1 production in a concentration-dependent manner. DHB was also found to induce the phosphorylation of Smad2, an important transcription factor involved in the production of type I procollagen. These results suggest that DHB may be a potential anti-wrinkle agent for topical application in the cosmetic industry.