In conclusion, 23-HTA protects against and attenuates UVA-induced oxidative stress in NHDFs likely via the nuclear factor erythroid-derived 2-like 2 signaling pathway.

Background: 6-Shogaol is a constituent of ginger that imparts the pungent flavor and a hydrolysis product of gingerols. This study aimed to investigate the potential of 6-shogaol as a natural cosmetic raw material by examining its anti-apoptotic, antioxidant, and anti-aging effects in human dermal fibroblasts (HDFs). Methods: Cell cycle analysis, ApoAlert caspase-3 colorimetric assay, and qRT-PCR analysis to assess the anti-apoptotic effects and qRT-PCR to measure the expression of SOD, CAT, and NRF2 to assess the antioxidant effects of 6-shogaol were performed; dichlorofluorescein diacetate was used to measure reactive oxygen species (ROS). Anti-aging effects were examined using qRT-PCR analysis to measure the expression of COL1A1 and MMP1 as well as using an SA-beta Gal assay. Results: 6-Shogaol showed no toxicity in HDFs at concentrations 5, 10, and 20 μM, and increased cell viability in a dose-dependent manner. qRT-PCR analysis showed that 6-shogaol pre-treatment downregulated the expression of BAX, caspase 3, and caspase 9 in a dose-dependent manner. Sub-G1 cells, which are rarely found in the normal cell cycle, decreased in a concentration-dependent manner after 6-shogaol pre-treatment, and treatment ameliorated the ROS increase observed upon UVA (10 J/cm 2) irradiation of HDFs and the expression of NRF2 increased in a dose-dependent manner. In addition, the expression of SOD and CAT, which are typical cellular antioxidant enzymes, increased. 6-Shogaol also increased the expression of COL1A1, the gene type 1 collagen in HDFs, and decreased the expression of MMP1, which codes for an enzyme that degrades type 1 collagen, thus promoting collagen formation. Conclusions: These results suggest that 6-shogaol can be used as a cosmetic material for preventing skin aging because of the cytoprotective, anti-apoptotic, and antioxidant effects in the HDFs identified in this study.