Antiskin Aging Effects of Indole Alkaloid N-Glycoside from Ginkgo Fruit (Ginkgo biloba fruit) on TNF-alpha-Exposed Human Dermal Fibroblasts

Abstract

Human skin aging has internal and external factors, both of which are characterized by TNF-alpha overproduction. Therefore, we aimed to identify a natural product that suppresses the damage that occurs in cutaneous dermal fibroblasts exposed to TNF-alpha. The protective effects of the indole alkaloid N-glycoside, ginkgoside B dimethyl ester (GBDE), isolated from ginkgo fruit (Ginkgo biloba fruit) were evaluated in TNF-alpha stimulated human dermal fibroblasts (HDFs). GBDE inhibited TNF-alpha-induced MMP-1 expression to 2.2 +/- 0.1-fold (p < 0.01) and reversed the decrease in collagen levels to 0.4 +/- 0.00-fold (p < 0.01) at 50 mu M. The effect of GBDE was due to the suppression of the phospolylaton of MAPKs (ERK, 0.47 +/- 0.05; JNK, 1.21 +/- 0.07; p38, 0.77 +/- 0.07-folds, p < 0.001) and Akt (0.14 +/- 0.03-fold, p < 0.001) compared to the TNF-alpha group. GBDE also reduced the expression of COX-2 to 2.06 +/- 0.12-fold (p < 0.001) and increased the expression of HO-1 to 10.64 +/- 0.2-fold (p < 0.001). In addition, GBDE inhibited the expression of the pro-inflammatory cytokines (IL-8, 2.2 +/- 0.0; IL-1 beta, 1.6 +/- 0.0; IL-6, 2.0 +/- 0.10-folds, p < 0.05). These results provide experimental evidence that GBDE can protect against skin damage, including aging.