Targeting inflammasome-mediated inflammation in psoriasis: Loganin as a novel iridoid glycoside-based therapeutic strategy

INTRODUCTION: Psoriasis is a multifactorial, chronic inflammatory skin disease characterized by epidermalhyperproliferation, keratinocyte differentiation abnormalities, and immune system dysfunction. The NLRP3 inflammasomecomplex has emerged as a key regulatory element in the pathogenesis of the disease. Current treatment options are oftenlimited by reduced long-term efficacy and undesirable side effects, underscoring the need for novel molecular targets.OBJECTIVE: This study sought to assess the therapeutic efficacy of Loganin (LOG), a natural iridoid glycoside, in animiquimod (IMQ)-induced psoriasis mouse model.MATERIALS& METHODS: Thirty-five BALB/c mice were randomly assigned to five groups: control, saline+vaseline (SAL+VAS),LOG, IMQ, and IMQ+LOG. Psoriatic inflammation was elicited by daily topical administration of IMQ for seven consecutivedays. The severity of the disease was evaluated utilizing the Psoriasis Area and Severity Index (PASI). Histopathological andmorphometric changes were examined through H&E and Masson’s trichrome staining, alongside volumetric assessmentusing the Cavalieri method. mRNA expression levels of NLRP3, ASC, caspase-1, IL-1β, gasdermin, TNF-α, and IL-17A werequantified via qPCR, and serum cytokine levels of IL-1β and IL-17A were measured using ELISA. NLRP3, ASC, caspase-1, andIL-1β expressions were assessed by immunohistochemistry. Furthermore, immunofluorescence staining for PCNA, CK-17,and VEGFR2 was measured utilizing ImageJ.RESULTS: LOG treatment significantly improved epidermal thickness, lymphocytic infiltration, collagen density, andvascularization.Immunohistochemical findings demonstrated a significant reduction in the expression of NLRP3, ASC, caspase-1, and IL-1βproteins. Consistently, qPCR results demonstrated downregulation of inflammasome-related genes and proinflammatorycytokines. Furthermore, immunofluorescence intensities of PCNA, CK-17, and VEGFR2 were significantly reduced. LOG alsodecreased serum levels of IL-1β and IL-17A, signifying a reduction in the systemic inflammation.CONCLUSION: The results revealed that LOG exhibits considerable anti-inflammatory effects via inhibiting NLRP3inflammasome activation and associated inflammatory pathways. LOG may serve as a new candidate for future antipsoriatic therapeutics focused on inflammasome-mediated cutaneous inflammation.Keywords: Imiquimod, Psoriasis, Loganin, Inflammation, NLRP3 inflammasome