Enhanced Mitochondrial Respiratory Metabolism in UVB-Damaged HDF cells Based on Metabolomics Analysis of Fermented Galla rhois gallnut Extract

Both natural aging and photoaging of the skin can lead to disruption of mitochondrial homeostasis, which in turn exacerbates skin aging. This study developed a novel fermented Galla rhois gallnut extract (FGRE) using Lactiplantibacillus plantarum with mitochondrial respiratory homeostasis amelioration. The results of biochemical experiments showed that FGRE had better antioxidant and anti-elastase activity compared to unfermented extract. Seahorse XF Cell Mito Stress Test demonstrated that 1% FGRE significantly enhanced mitochondrial respiratory function in UVB-irradiated human dermal fibroblasts (HDFs) compared to unfermented extract (21% increase in basal respiration and spare respiratory capacity, 26% increase in ATP production, and 30%increase in maximal respiration). The non-targeted metabolomics analysis revealed differential metabolites predominantly enriched in amino acid metabolic pathways, and obviously increased metabolites were leucinic acid, Val-Asn, Arg-Val-Phe, Urolithin A (UroA), Urolithin M5 (UroM5) and other flavonoids. The quantitative detection showed that the levels of UroA (0.49 ng/mL) and its derivative UroM5 (8.35 ng/mL) were quite low, while the concentration of leucinic acid was about 97.20 μg/mL. And cell experiments suggested that 1 μg/mL leucinic acid (equivalent to concentration in 1% FGRE) ameliorated UVB-induced mitochondrial respiratory dysfunction in HDFs, that determine leucine as primary bioactive constituent. These results indicated that FGRE had potential anti-aging capacity by enhancing mitochondrial function, which also provided a novel candidate for dermo-cosmetic applications.