Galangin attenuates UVB-induced skin photoaging through SIRT1-dependent LC3 deacetylation and autophagy modulation
Su-Ying Wen1, Shang-Chuan Ng2, Mei-Hsin Su2
1Department of Dermatology, Taipei City Hospital, Zhongxing Branch, Taipei, Taiwan, ROC; University of Taipei, Taipei, Taiwan, ROC; Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan, ROC.
Background:
Ultraviolet B (UVB) irradiation is a major contributor to skin photoaging by promoting oxidative stress, extracellular matrix degradation, and cellular senescence. Sirtuin 1 (SIRT1), an NAD⁺-dependent deacetylase, is a key regulator of cellular homeostasis and autophagy and represents an important target for phytochemical-based interventions.
Purpose:
The present study investigated whether galangin, a naturally occurring flavonoid, protects against UVB-induced photoaging by modulating SIRT1-associated autophagy in human dermal fibroblasts (HDFs) and in mouse skin.
Methods:
The effects of galangin were evaluated in UVB-irradiated HDFs and a UVB-induced mouse photoaging model. Oxidative stress, cellular senescence, collagen content, and photoaging-related biomarkers were assessed. Autophagy was investigated using pharmacological inhibition, siRNA-mediated knockdown of SIRT1 or LC3, immunoprecipitation analysis of LC3 acetylation, and acetylation/deacetylation-mimetic LC3 mutants.
Results:
Galangin attenuated UVB-induced oxidative stress, cellular senescence, MMP accumulation, and collagen degradation in HDFs. Pharmacological inhibition of autophagy or silencing of SIRT1 or LC3 abolished the protective effects of galangin. Mechanistically, galangin promoted SIRT1-dependent deacetylation of LC3, thereby enhancing autophagic flux and facilitating MMP clearance. Moreover, the deacetylation-mimetic LC3 mutant (K49R/K51R) enhanced autophagy and recapitulated the protective effects of galangin, whereas the acetylation-mimetic mutant (K49Q/K51Q) attenuated these effects. In UVB-irradiated mouse skin, topical galangin increased SIRT1 expression while reducing MMP-1, MMP-3, and 8-OHdG levels.
Conclusion:
Galangin protects against UVB-induced photoaging through SIRT1-mediated LC3 deacetylation and enhanced autophagic flux. These findings identify a previously unrecognized SIRT1-LC3-autophagy axis and provide a molecular rationale for the further development of galangin-based strategies for skin photoaging prevention.
