Abstract

Introduction Psoriasis is a prevalent chronic inflammatory skin disease in which pattern recognition receptors, particularly the NLRP3 inflammasome, are increasingly implicated in disease pathogenesis. Solanum nigrum (SN) has been used in traditional and clinical practice for psoriasis treatment, but its therapeutic mechanisms and key active constituents remain unclear. This study investigated the anti-psoriatic mechanisms of SN and identified its major bioactive component. Methods NLRP3 inflammasome activation in psoriasis was evaluated using public transcriptomic datasets and clinical skin biopsies. The therapeutic effects of SN were assessed in imiquimod-induced primary and relapse psoriasis-like dermatitis models. Bulk RNA sequencing of lesional skin was performed to identify SN-regulated pathways. SN was chemically characterized by UPLC–MS, and candidate active compounds were prioritized by molecular docking and molecular dynamics simulation. Results NLRP3 inflammasome activation was consistently elevated in psoriatic lesions in both public datasets and clinical specimens. SN markedly alleviated disease severity in primary and relapse models, reduced keratinocyte hyperproliferation, and lowered systemic inflammatory cytokine levels. Transcriptomic analysis showed that SN mainly modulated PRR/NLR-related signaling pathways. Mechanistically, SN inhibited NLRP3 inflammasome activation and decreased IL-1β and IL-18 production. Integrated chemical, biological, and computational analyses identified trigonelline as a major active constituent contributing to the anti-psoriatic effects of SN. Discussion SN ameliorates psoriasis-like dermatitis primarily through suppression of NLRP3 inflammasome signaling, with trigonelline identified as a key contributory active component. These findings provide mechanistic support for the therapeutic application of SN in psoriasis.