5,2′,5′-Trihydroxy-7,8-Dimethoxyflavanone Isolated from Scutellaria indica L. Protects Skin Keratinocytes from H2O2-Induced Oxidative Stress in Association with Nrf2/ARE Pathway

Although flavonoids from Scutellaria baicalensis are well known for their antioxidant properties, the active constituents and biological effects of its congeneric species, Scutellaria indica L. (S. indica), remain unclear. In this study, we investigated the antioxidant functions and cytoprotective effects of 5,2′,5′-trihydroxy-7,8-dimethoxyflavanone (TDF), a flavanone constituent of S. indica, against oxidative stress. Among six Scutellaria-derived compounds screened, TDF produced the highest antioxidant response element (ARE)-reporter activity in HepG2 cells, and it upregulated the expression of Nrf2 target genes in HaCaT cells. In an H2O2-induced oxidative stress model, TDF suppressed ROS and reversed the H2O2-induced reduction in total Nrf2 protein. Additionally, TDF showed SOD-like activity and modest elastase-inhibitory activity in cell-free assays and was classified as a non-irritant in a 3D-reconstructed human epidermis model. Overall, these results indicate that TDF is a bioactive constituent of S. indica that protects keratinocytes against oxidative stress, and that this protective effect is associated with the regulation of the Nrf2/ARE pathway.