Effect of Oxyresveratrol on Inflammatory Skin Diseases

Abstract

Background: Oxyresveratrol (ORV) is one of the novel antioxidants having been extensively studied in recent years. One of the main sources of ORV is Artocarpus lakoocha, which has been used in traditional medicine in Thailand for decades. However, the role of ORV in skin inflammation has not been clearly demonstrated. Therefore, we investigated the anti-inflammatory effects of ORV on dermatitis model.

Objectives: To determine the effect and mechanism of ORV on anti-proliferation, anti-inflammation and anti-Staphyloccocus aureus with keratinocytes and to clarify the treating efficacy of ORV on skin inflammatory mouse model.

Materials and methods: The effect of ORV was examined on human immortalized and primary skin cells exposed to bacterial components including peptidoglycan (PGN) and lipopolysaccharide (LPS). PGN and LPS were used to induce inflammation on immortalized keratinocytes (HaCaT) and human epidermal keratinocytes (HEKa). We then performed MTT assay, Annexin V and PI assay, cell cycle analysis, real-time PCR, ELISA and Western blot in these in vitro models. On mouse model, 2,4-Dinitrochlorobenzene (DNCB) was used to induce dermatitis. H&E staining, immunohistochemistry (IHC) staining with CD3, CD4 and CD8 markers were used to evaluate the effects of ORV in in vivo model of skin inflammation using BALB/c mice. Disc diffusion method on Staphyloccocus aureus was used to test the anti-bacterial effect of ORV.

Results: Treatment with ORV on HaCaT cells showed the anti-proliferation effect through inducing apoptosis by activating caspase-3. Pretreatment of HaCaT and HEKa cells with ORV inhibited pro-inflammatory cytokine production through inhibition of NF-κB pathway. In DNCB-induced dermatitis mouse model, ORV treatment reduced severity of skin lesion, and skin thickness and numbers of CD3, CD4 and CD8 T cells in the sensitized skin of mice. The combination of ORV and several antibiotics at the dosage using on keratinocytes showed the synergestic effect on anti-Staphyloccocus aureus through the increase of inhibiting zone.

Conclusion: ORV treatment can ameliorate inflammation in the in vitro models of skin inflammation and in vivo models of dermatitis, suggesting a therapeutic potential of ORV for treatment of skin diseases particularly eczema. ORV can facilitate the anti-bacterial property of antibiotics on Staphylococcus aureus.