OBJECTIVE To investigate the anti-inflammatory mechanisms of demethylzeylasteral (Dem) in ulcerative colitis (UC) and collagen-induced arthritis (CIA), focusing on its regulation of Th17 cell differentiation and associated signaling pathways.

METHODS UC was induced in C57BL/6 mice using dextran sulfate sodium (DSS), and Dem was administered by gavage at low (1 mg ·kg^-1) or high (2 mg ·kg^-1) doses. Disease severity was assessed by body weight loss, colon length, and stool consistency. Serum cytokines (TNF-α, IL-1β, IL-6) were quantified by ELISA, and Th17 cell ratio in mesenteric lymph nodes was determined by flow cytometry. The anti-inflammatory efficacy of Dem was further validated using a CIA mouse model. The efficacy of Dem was further verified in the CIA model, and the expression of JAK2 and STAT3 was intervened by siRNA to investigate its mechanism of action in Th17 differentiation.

RESULTS Dem-treated mice showed reduced weight loss and colon shortening, and decreases in serum TNF-α, IL-1β, and IL-6 levels (P < 0.01) and Th17 cell proportion (P < 0.01). Western blot and siRNA assays showed that Dem significantly inhibited the differentiation and activation of Th17 cells by suppressing the phosphorylation of the JAK2-STAT3 pathway. Dem also significantly alleviated arthritis symptoms and related markers in the CIA model, confirming its anti-inflammatory effects.

CONCLUSION Dem improves UC and rheumatoid arthritis by downregulating the JAK2-STAT3 signaling pathway, inhibiting Th17 cell differentiation and pro-inflammatory cytokine expression, suggesting its potential therapeutic value in immune-related diseases.