The potential of Diosgenin in treating psoriasis: Studies from HaCaT keratinocytes and imiquimod-induced murine model

Abstract

AimsPsoriasis is a cutaneous disease mainly characterized by keratinocyte hyperproliferation, abnormal epidermal differentiation, inflammation and angiogenesis. In this study, we aimed to report the therapeutic potential of Diosgenin on psoriasis-like models and explore the underlying mechanisms. Main methodsFor in vitro studies, we initially evaluated the bioeffects of Diosgenin on keratinocytes by detecting the cell viability, cell cycle and apoptosis in HaCaT cells. To mimic psoriatic conditions, we established hyperproliferative model by stimulating HaCaT cells with LPS/IL-22 and inflammatory model by LPS/TNF-α stimulation. Meanwhile, differentiation in HaCaT cells and angiogenesis in HUVECs/HMEC-1 were observed. The influence of Diosgenin on above-mentioned conditions was examined. For in vivo studies, we dosed imiquimod (IMQ) -induced mice with Diosgenin and conducted hematoxylin-eosin (HE), TUNEL assay and immunohistochemistry (IHC) to evaluate histological changes, apoptosis and the status of keratinocyte proliferation, epidermal differentiation, vascularity and cutaneous inflammatory cell infiltration respectively. Key findingsResults showed that Diosgenin inhibited HaCaT cell growth through cell cycle arrest and NFκB inhibition while induced apoptosis by regulating Caspase3, Bax and Bcl-2 protein expression. After Diosgenin treatment, NFκB nuclear translocation and IL-22 receptor dependent pathways were suppressed in LPS/IL-22 induced HaCaT cells respectively. Furthermore, Diosgenin downregulated proinflammatory cytokines through TLR4/Myd88 inhibition and upregulated several differentiation markers' expression in HaCaT cells. Additionally, Diosgenin inhibited vascular formation partially by reducing the VEGF-α expression in keratinocytes. In animal studies, Diosgenin attenuated psoriatic lesions on mice accordingly. SignificanceThis study suggests that Diosgenin might be a promising candidate for developing anti-psoriatic agents.