669 Paeoniflorin suppresses keratin 17 expression via NF-kB pathway and exerts anti-psoriatic effect

Abstract

Psoriasis, affecting 2%-3% of the population worldwide, is an autoimmune inflammatory skin disease characterized by hyperproliferation of epidermal keratinocytes. Regarding the complexity of disease pathogenesis, there is still no curative therapy for psoriasis. Paeoniflorin (PF), a traditional Chinese herbal medicine, which is the main bioactive component of the total glucosides of peony, is extracted from Paeonia lactiflora Pall (Family: Ranunculaceae). This agent has been shown to have various pharmacological effects, including anti-inflammatory, anti-phlogistic, and anti-apoptotic effects. In the present study, we aimed to illustrate the effect and mechanism of PF on keratinocyte proliferation and immunological activity. In IMQ-induced psoriasis-like lesions, epidermal thickness was reducing to 50% as compared with control groups after topical application of PF. Consistently, dermal infiltrated lymphocytes was markedly reduce. Here we showed that PF could inhibit the proliferation of human keratinocyte cell line HaCaT in a dose-dependent manner. To further clarify the related mechanism, we evaluated the effect of PF on the expression of psoriasis-related hyperproliferation marker K17. Interestingly, K17 protein and mRNA levels were significantly downregulated in HaCaT cells after application of PF. Besides, PF showed inhibitory effect on the inflammatory function of keratinocytes, representing by reduced activation of NF-kB signaling pathways, such as phosphorylated NF-kB p65 and phosphoryalated-IkB. Together, our findings uncovers a previous unrecognized role of PF on inhibiting the proliferation and inflammation of keratinocytes by targeting K17, suggesting that PF might be a potential target in the treatment of psoriasis.