Diosmetin, a novel transient receptor potential vanilloid 1 antagonist, alleviates the UVB radiation-induced skin inflammation in mice

UVB radiation-mediated inflammation and the oxidative process involve the transient receptor potential vanilloid 1 (TRPV1) channel activation in neuronal and non-neuronal cells. Once diosmetin has been identified as a novel TRPV1 antagonist, we evaluated the action of diosmetin from the inflammatory [ear oedema, myeloperoxidase (MPO) activity, histological changes, and cytokines levels] and oxidative [nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and SOD activities] parameters in mice exposed to UVB radiation (0.5 j/cm(2)). We also verified the action of diosmetin on UVB radiation-induced inflammatory parameters after cutaneous nerve fibers denervation by RTX (50 mu g/kg s.c.). The topical treatment with the novel TRPV1 antagonist, diosmetin (1%; 15 mg/ear), reduced ear oedema, MPO activity, and MIP-2 and IL-1 beta cytokines levels by 82 +/- 8%, 59 +/- 10%, 40 +/- 12%, and 85 +/- 9%, respectively. The action of diosmetin on ear oedema and inflammatory cell infiltration was histologically confirmed. Topical diosmetin (1%) also reduced NADPH oxidase activity by 67 +/- 10% and reverted SOD activity by 81 +/- 13%. After cutaneous nerve fibers denervation using RTX, diosmetin reduced ear oedema, but not the inflammatory cell infiltration in mice exposed to UVB radiation. Diosmetin can be a promising molecule against skin inflammatory disorders as a result of sunburn induced by UVB radiation exposure.