Ginsenoside Rb₁ induces type I collagen expression through peroxisome proliferator-activated receptor-delta.

Wrinkle formation is one of the primary characteristics of skin aging, the major cause of wrinkle is the loss of structural protein type I collagen in dermal layer of skin. Topical application of natural substances to reduce wrinkle is gaining attention in recent years. Although a number of polyphenoic compounds are suggested to prevent ultraviolet-induced wrinkle, very few of them are able to increase type I collagen synthesis directly. Ginseng has been known in folk medicine of its beneficial effect to skin. The present study investigate the effect of ginsenoside on type I collagen induction in human dermal fibroblasts. Ginsenoside Rb₁ was shown to induce type I collagen expression in dermal fibroblasts in a dose- and time-dependent manner. Recent studies suggest the important post-transcriptional regulatory role of microRNAs; here we demonstrated that miR-25 can directly inhibit type I collagen protein expression, and treatment of fibroblasts with Rb₁ can reduce the inhibition by decreasing miR-25 level. Furthermore, we identified that the nuclear receptor, peroxisome proliferator-activated receptor-delta (PPARδ) is the key mediator of Rb₁-induced type I collagen expression. Knockdown of PPARδ by small-interference RNA abolished the Rb₁-induced type I collagen production and reversed the Rb₁-suppressed miR-25 expression. These results demonstrated that ginsenoside Rb₁ can increase target gene expression through transcriptional pathway, at the same time, inhibit the corresponding miRNA expression to minimize the translation repression. Furthermore, this study provide solid support of ginsenoside Rb₁-induced type I collagen expression, which warrant further study in the dermatological application of ginsenosides in skin disorders.