Abstract

Background Psoriasis is a chronic, immune-mediated skin disease with a significant tendency to relapse, posing a substantial challenge for long-term management. Pectolinarigenin (PEC), a plant-derived natural flavonoid, has demonstrated various pharmacological activities, yet its efficacy and mechanisms against psoriasis remain incompletely understood. Objective This study aimed to investigate the therapeutic potential of PEC against psoriasis and to elucidate the underlying molecular mechanisms, with a focus on its role in modulating key inflammatory and proliferative pathways. Methods The anti-psoriatic efficacy of PEC was evaluated in vivo in an IMQ-induced psoriasis-like mouse model through Psoriasis Area and Severity Index (PASI) scoring, histopathological examination, and measurement of inflammatory and proliferative markers. In vitro , IL-17A and IL-22-stimulated HaCaT cells were used to investigate the modulatory effects of PEC on inflammatory responses and cell proliferation. Results PEC administration significantly alleviated IMQ-induced psoriatic symptoms, reduced epidermal thickness, suppressed keratinocyte hyperproliferation, and downregulated pro-inflammatory cytokines in mouse skin. Mechanistic investigations revealed that PEC inhibited the activation of STAT3, NF-κB, and ERK signaling pathways in both psoriatic-like mouse skin tissues and cellular models. Moreover, PEC downregulated FABP5 expression in keratinocytes, whereas FABP5 overexpression partially attenuated the anti-psoriatic effects of PEC, suggesting that FABP5 may contribute to the anti-inflammatory and anti-proliferative actions of PEC. Conclusions These findings demonstrate that PEC alleviates psoriasis-like skin lesions by inhibiting activation of STAT3, NF-κB, and ERK signaling pathways and downregulating FABP5 expression, highlighting PEC as a promising therapeutic candidate for psoriasis.