Trans-chalcone added in topical formulation inhibits skin inflammation and oxidative stress in a model of ultraviolet B radiation skin damage in hairless mice

Abstract

Trans-chalcone (TC) is a common precursor of flavonoids. However, the pharmacological properties of TC remain to be fully understood. The present study investigated whether topical formulation containing TC (TFcTC) presents therapeutic effect in UVB radiation-induced skin damage using disease, enzyme activity, antioxidant activity, protein and mRNA parameters. Control topical formulation (CTF) and TFcTC were applied in hairless mice before and after exposure to UVB radiation. Dorsal skin samples were collected after UVB exposure to evaluate: i) skin edema (weight) was measured by punch biopsy; ii) spectrophotometric assays were used to measure myeloperoxidase (MPO) and catalase activities, ferric (FRAP) and ABTS cation reducing antioxidant power, superoxide anion production and levels of reduced glutathione (GSH); iii) enzymography was used to measure matrix metalloproteinase-9 (MMP-9) activity; iv) chemiluminescence was used to measure the lipid peroxidation (LPO); v) enzyme-linked immunosorbent assay (ELISA) was used to measure tumor necrosis factor alpha (TNF-α) levels; vi) reverse transcription quantitative PCR (RT-qPCR) was used to measure cyclooxygenase-2 (COX-2), gp91phox (NADPH oxidase sub-unity), glutathione peroxidase-1 (Gpx1), glutathione reductase (Gr), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) mRNA expression. TFcTC inhibited UVB-induced skin edema, MPO activity, MMP-9 activity, TNF-α production, and COX-2 mRNA expression. TFcTC inhibited UVB-induced LPO, down-regulated superoxide anion levels and gp91phox mRNA expression, and improved antioxidant potential and GSH skin levels. The mRNA expression of detoxification systems such as Nrf2, HO-1, Gpx1 and Gr, and catalase activity were also enhanced by treatment with TFcTC. In conclusion, TFcTC protects mice skin from UVB radiation by inhibiting inflammation, and improving antioxidant and detoxification systems. Therefore, topical treatment with TC is a novel therapeutic approach for the treatment of UVB radiation skin damages, which merits further pre-clinical and clinical investigation.