EGb-761 prevents ultraviolet B-induced photoaging via inactivation of mitogen-activated protein kinases and proinflammatory cytokine expression

• Published in: Journal of dermatological science 2014-07, Vol.75 (1), p.55-62
• Main Authors: Chen, Chih-Chiang, Chiang, An-Na, Liu, Han-Nan, Chang, Yun-Ting
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Antioxidants - pharmacology; BALB/c mice; Cell Line; Cytokines; Cytokines - metabolism; Dermatology; EGb-761; Enzyme Activation; Fibroblasts - drug effects; Fibroblasts - enzymology; Fibroblasts - immunology; Fibroblasts - radiation effects; Humans; Inflammation Mediators - metabolism; Male; Matrix metalloproteinase; Matrix Metalloproteinase 1 - metabolism; Mice, Inbred BALB C; Mitogen activated protein kinase; Mitogen-Activated Protein Kinases - metabolism; Phosphorylation; Plant Extracts - pharmacology; Reactive Oxygen Species - metabolism; Signal Transduction - drug effects; Skin - drug effects; Skin - enzymology; Skin - immunology; Skin - pathology; Skin - radiation effects; Skin Aging - drug effects; Skin Aging - radiation effects; Sunscreening Agents - pharmacology; Time Factors; Ultraviolet irradiation; Ultraviolet Rays - adverse effects
• ISSN: 0923-1811; 1873-569X
• DOI: 10.1016/j.jdermsci.2014.04.001

Abstract Background EGb-761 is an antioxidant and anticarcinogen; however, its role as a photoprotector remains unknown. Objective To determine whether EGb-761 photoprotects human dermal fibroblasts and BALB/c mice skin against ultraviolet B (UVB) light irradiation. Methods To simulate chronic photodamage, shaved BALB/c mice were exposed to UVB irradiation (90 mJ/cm2 ) thrice weekly for 3 months. EGb-761 (2 mg/cm2 ) was topically applied 1 h before irradiation to evaluate its effect. The mechanisms by which EGb-761 protects the skin from photodamage were evaluated by immunohistochemical analysis, enzyme-linked immunosorbent assay (ELISA), and Western blotting. Results In BALB/c mice, the signs of photoaging or photodamage, such as coarse wrinkle formation, epidermal hyperplasia, and elastic fiber degeneration, markedly reduced with the topical application of EGb-761. Western blot and ELISA revealed that the activation of MMP-1 in cultured fibroblasts markedly diminished after pretreatment with EGb-761. In addition, EGb-761 inhibited UVB-induced overexpression by the fibroblasts of the proinflammatory cytokines, such as interleukin (IL)-1α, IL-1β, IL-6, and tumor necrosis factor-α. The phosphorylation of the mitogen-activated protein kinase (MAPK) signal transduction pathway components, including extracellular signal-regulated kinase, C-Jun N-terminal kinase, and p38, which are induced by UV irradiation, was significantly inhibited in vivo and in vitro . EGb-761 also diminished the generation of UVB-induced reactive oxygen species (ROS). Conclusions EGb-761 photoprotects mice and cultured fibroblasts, inhibits the UVB-induced phosphorylation of MAPK pathway components, and reduces the expression of the proinflammatory cytokines by suppressing ROS generation. Thus, topically applied EGb-761 may be a promising photoprotective agent.