Enhanced mitochondrial respiratory metabolism in UV-damaged HDF cells based on metabolomics analysis of fermented Galla rhois gallnut extract

UV-induced photoaging disrupts mitochondrial homeostasis in skin cells, which in turn exacerbates skin aging. In this study, we developed a novel fermented Galla rhois gallnut extract (FGRE) using Lactiplantibacillus plantarum with mitochondrial respiratory homeostasis amelioration. Biochemical assays showed that FGRE exhibited stronger antioxidant and anti-elastase activities than the unfermented extract. Using Seahorse XF Cell Mito Stress Test, 1% FGRE significantly enhanced mitochondrial respiratory function in UVB-irradiated human dermal fibroblast (HDF) cells compared to that with the unfermented extract. In addition, 1% FGRE increased the ATP content and NAD + /NADH ratio and regulated the transcription level of fusion and fission genes in UVA-induced HDFs. Furthermore, the non-targeted metabolomics analysis revealed that differential metabolites were predominantly enriched in amino acid metabolic pathways, and 24 differential metabolites were putatively identified. Among these, the differential metabolites leucinic acid, urolithin A, and urolithin M5 were quantitatively determined. Notably, 1 μg/mL leucinic acid (equivalent to the concentration in 1% FGRE) ameliorated mitochondrial respiratory dysfunction and promoted the ATP production in UV-induced HDFs. Therefore, leucinic acid was considered as one of the potentially bioactive metabolites of FGRE.