Abstract
UV radiation and H2O2 are the primary factors that cause skin aging. Both trigger oxidative stress and cellular aging. It has been reported that deacetylase silent information regulator 1 (SIRT1), a longevity gene, enhances activation of NF-E2-related factor-2 (Nrf2), as well as its downstream key antioxidant gene hemeoxygenase-1 (HO-1), to protect cells against oxidative damage by deacetylating the transcription coactivator PPARγ coactivator-1α (PGC-1α). Galangin, a flavonoid, possesses anti-oxidative and anti-inflammatory potential. In the present study, we applied Ultraviolet B/H2O2-induced human dermal fibroblast damage as an in vitro model and UVB-induced photoaging of C57BL/6J nude mice as an in vivo model to investigate the underlying dermo-protective mechanisms of galangin. Our results indicated that galangin treatment attenuates H2O2/UVB-induced cell viability reduction, dermal aging, and SIRT1/PGC-1α/Nrf2 signaling activation. Furthermore, galangin treatment enhanced Nrf2 activation and nuclear accumulation, in addition to inhibiting Nrf2 degradation. Interestingly, upregulation of antioxidant response element luciferase activity following galangin treatment indicated the transcriptional activation of Nrf2. However, knockdown of SIRT1, PGC-1α, or Nrf2 by siRNA reversed the antioxidant and anti-aging effects of galangin. In vivo evidence further showed that galangin treatment, at doses of 12 and 24 mg/kg on the dorsal skin cells of nude mice resulted in considerably reduced UVB-induced epidermal hyperplasia and skin senescence, and promoted SIRT1/PGC-1α/Nrf2 signaling. Furthermore, enhanced nuclear localization of Nrf2 was observed in galangin-treated mice following UVB irradiation. In conclusion, our data indicated that galangin exerts anti-photoaging and antioxidant effects by promoting SIRT1/PGC-1α/Nrf2 signaling. Therefore, galangin is a potentially promising agent for cosmetic skin care products against UV-induced skin aging.
Highlights
Skin senescence is a progressive and complicated biological process, which is regulated by both intrinsic and extrinsic factors, leading to cumulative structural and physiological changes in skin layer and appearance [1]
Sci. 2022, 23, x FOR PEEpRoRsEitVivIEeWcells, which was reversed following the knockdown of Sirt1 or PGC-1α (Figure 6B). 4 of 6 These results indicated that the induction of NF-E2-related factor-2 (Nrf2) in attenuating aging is mediated via Sirt1 and PGC-1α signaling in dermal fibroblast cells exposed to H2O2
We found that treatment with galangin, a natural flavonoid derived from Alpinia officinarum, considerably alleviates the deleterious effects induced in both in vitro and in vivo models
Summary
Skin senescence is a progressive and complicated biological process, which is regulated by both intrinsic and extrinsic factors, leading to cumulative structural and physiological changes in skin layer and appearance [1]. Intrinsic aging tends to intensify with advancing age, whereas extrinsic aging is primarily caused by exposure to UV irradiation from the sun [2]. Both these factors cause the accumulation of reactive oxygen species, which in turn leads to structural damage to proteins and DNA [3]. Senescent cells exhibit a robust inflammatory response, reduction in antioxidant-related gene expression, and higher secretion of matrix metalloproteinases (MMPs), which enable the degradation of the extracellular matrix (ECM) in the dermal skin layer [4]. HO-1, a redox-sensitive inducible protein encoded by ARE promoter regulatory elements, protects dermal fibroblast cells against stressinduced oxidative damage [11]. Enhancement of antioxidant capacity in the skin by natural compounds may serve as a promising strategy for treating stress-induced oxidative damage
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