Paris saponin VII attenuates psoriasiform inflammation by regulating STAT3/NFκB signaling pathway and Caspase-1-induced pyroptosis

Psoriasis is a significant global health challenge due to limited treatment efficacy. Paris saponin VII (PSVII) shows anti-inflammatory and anti-proliferative potential but its role in psoriasis is unclear. In this study, PSVII was identified from a library of natural compounds as a therapeutic candidate for psoriasis. In a murine model, PSVII reduced skin lesion severity, epidermal thickness, and inflammatory factor expression, preliminaryly indicating its anti-inflammatory properties. In vitro, PSVII inhibited HaCaT cell hyperproliferation, regulated the cell cycle, induced apoptosis, and modulated reactive oxygen species (ROS). Bioinformatics analyses suggested that signal transducer and activator of transcription 3 (STAT3), cysteine aspartate specific protease 1 (Caspase-1), and the process of pyroptosis are likely targets and mechanisms of PSVII action. PSVII could reduce cell mortality in psoriatic cells and lowered expression levels of NLR Family Pyrin Domain Containing 3 (NLRP3), Caspase-1, Gasdermin D (GSDMD), Interleukins (IL)-18, and IL-1β, underscoring its potential role in modulating pyroptosis within these cells. Mechanistically, PSVII may suppress the STAT3/nuclear factor kappa B (NFκB) signaling pathway. Consequently, PSVII plays a significant role in psoriasis management. PSVII could modulate pyroptotic cell death in psoriatic cells by targeting the STAT3/NFκB signaling cascade, leading to anti-inflammatory and anti-proliferative effects, and thereby ameliorating psoriasis symptoms.