Limonin ameliorates ulcerative colitis by regulating STAT3/miR-214 signaling pathway

Area of Science:

• Gastroenterology
• Immunology
• Pharmacology

Background:

• Ulcerative colitis (UC), a prevalent inflammatory bowel disease (IBD), poses a significant global health challenge.
• Limonin, a citrus-derived triterpenoid, exhibits anti-inflammatory and anti-apoptotic properties, but its role in UC treatment is not well-defined.

Purpose of the Study:

• To investigate the therapeutic efficacy of limonin in a dextran sodium sulfate (DSS)-induced mouse model of ulcerative colitis.
• To elucidate the underlying molecular mechanisms by which limonin exerts its protective effects against UC.

Main Methods:

• In vivo studies involved assessing disease activity index (DAI), colon length, histology, and cytokine levels in DSS-treated mice receiving limonin.
• In vitro experiments examined the effect of limonin on pro-inflammatory cytokine production in normal colonic epithelial cells.
• Mechanistic studies focused on analyzing the modulation of p-STAT3 and miR-214 signaling pathways by limonin.

Main Results:

• Limonin treatment significantly ameliorated UC symptoms, reducing DAI, colon shortening, and histological damage.
• Limonin administration suppressed elevated levels of pro-inflammatory cytokines, including TNF-α and IL-6, in vivo and in vitro.
• The therapeutic effect of limonin in UC was primarily attributed to the downregulation of p-STAT3 and miR-214.

Conclusions:

• Limonin demonstrates significant therapeutic potential for ulcerative colitis, effectively mitigating inflammation and tissue damage.
• The findings suggest that limonin acts by inhibiting the p-STAT3/miR-214 signaling pathway.
• Limonin represents a promising novel therapeutic agent for clinical translation in managing UC.