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

Chih-Chiang Chen; An-Na Chiang; Han-Nan Liu; Yun-Ting Chang

doi:10.1016/j.jdermsci.2014.04.001

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

J Dermatol Sci. 2014 Jul;75(1):55-62. doi: 10.1016/j.jdermsci.2014.04.001. Epub 2014 Apr 13.

Authors

Chih-Chiang Chen¹, An-Na Chiang², Han-Nan Liu³, Yun-Ting Chang⁴

Affiliations

¹ Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, ROC; Department of Dermatology, National Yang Ming University, Taipei, Taiwan, ROC; Department of Dermatology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
² Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan, ROC.
³ Department of Dermatology, National Yang Ming University, Taipei, Taiwan, ROC; Department of Dermatology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
⁴ Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, ROC; Department of Dermatology, National Yang Ming University, Taipei, Taiwan, ROC; Department of Dermatology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. Electronic address: ytchang@vghtpe.gov.tw.

PMID: 24802711
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 (90mJ/cm(2)) thrice weekly for 3 months. EGb-761 (2mg/cm(2)) was topically applied 1h 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.

Keywords: BALB/c mice; Cytokines; EGb-761; Matrix metalloproteinase; Mitogen activated protein kinase; Ultraviolet irradiation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Inflammatory Agents / pharmacology
Antioxidants / pharmacology
Cell Line
Cytokines / metabolism*
Enzyme Activation
Fibroblasts / drug effects
Fibroblasts / enzymology
Fibroblasts / immunology
Fibroblasts / radiation effects
Ginkgo biloba
Humans
Inflammation Mediators / metabolism*
Male
Matrix Metalloproteinase 1 / metabolism
Mice, Inbred BALB C
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 Rays / adverse effects*

Substances

Anti-Inflammatory Agents
Antioxidants
Cytokines
Inflammation Mediators
Plant Extracts
Reactive Oxygen Species
Sunscreening Agents
Ginkgo biloba extract
Mitogen-Activated Protein Kinases
Matrix Metalloproteinase 1