By establishing an effective ultraviolet B (UVB) radiation model of skin damage in mice, the effect of lemon peel flavonoids (LPF) on skin damage was explored. UVB skin damage in UV-irradiated mice was simulated, and animal models were established. Serum parameters were measured using kits, skin sections were stained with hematoxylin-eosin (H&E) and Masson, and quantitative polymerase chain reaction (qPCR) was used to detect the expression of skin tissue-related mRNA. The experimental results showed that LPF increased the activity of catalase (CAT) and superoxide dismutase (SOD) oxidases in serum of mice with UVB-induced skin damage and decreased MDA, interleukin-1β (IL-1β), IL-6, IL-10, and tumor necrosis factor-alpha (TNF-α) levels. Pathological observation indicated that LPF alleviated the skin tissue lesions caused by UVB. LPF upregulated the mRNA expression of SOD1, SOD2, CAT, nuclear factor erythroid-2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and inhibitor of NF-κB alpha (IκB-α) and downregulated the expression of nuclear factor kappa B (NF-κB), p38 MAPK, and cyclooxygenase-2 (COX-2) in the skin tissue of skin-damaged mice. There was a greater protective effect of LPF on the skin as compared to vitamin C (VC) at the same application concentration, and the effect of LPF was positively correlated with the concentration. High performance liquid chromatography (HPLC) analysis showed that LPF contained five flavonoid compounds, namely isomangiferin, rutin, astragalin, naringin, and quercetin. We demonstrated that flavonoids from LPF exhibit an excellent skin protection effect with satisfactory application value.
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