Topical astilbin ameliorates imiquimod-induced psoriasis-like skin lesions in SKH-1 mice via suppression dendritic cell-Th17 inflammation axis.

ABSTRACT

Astilbin, an essential component of Rhizoma smilacis glabrae, exerts significant antioxidant and anti-inflammatory effects against various autoimmune diseases. We have previously reported that astilbin decreases proliferation and improves differentiation of HaCaT keratinocytes in a psoriatic model. The present study was designed to evaluate the potential therapeutic effects of topical administration of astilbin on an imiquimod (IMQ)-induced psoriasis-like murine model and to reveal their underlying mechanisms. Topical administration of astilbin at a lower dose alleviated IMQ-induced psoriasis-like skin lesions by inducing the differentiation of epidermal keratinocytes in mice, and the therapeutic effect was even better than that of calcipotriol. Moreover, the inflammatory skin disorder was relieved by astilbin treatment characterized by a reduction in both IL-17-producing T cell accumulation and psoriasis-specific cytokine expression in skin lesions. Furthermore, we found that astilbin inhibited R837-induced maturation and activation of bone marrow-derived dendritic cells and decreased the expression of pro-inflammatory cytokines by downregulating myeloid differentiation factor 88. Our findings provide the convincing evidence that lower doses of astilbin might attenuate psoriasis by interfering with the abnormal activation and differentiation of keratinocytes and accumulation of IL-17-producing T cells in skin lesions. Our results strongly support the pre-clinical application of astilbin for psoriasis treatment.