FHND5032 is an orally active miR-124 inducer that significantly enhances miR-124 expression in macrophages. It inhibits the PIK3R2/PI3K/Akt axis to block inflammatory signaling, facilitates macrophage reprogramming, and restores epithelial barrier function. FHND5032 alleviates colitis and reduces inflammatory burden in ulcerative colitis mouse models, making it useful for ulcerative colitis research.

FHND5032 (0-20 μM, 24 h) significantly enhances anti-inflammatory activity by increasing miR-124 expression in THP-1 and RAW 264.7 cells. At concentrations of ≤ 5 μM, FHND5032 targets PIK3R2 to activate miR-124-5p expression, regulating the PI3K/Akt pathway during the reprogramming of THP-1 and RAW 264.7 cells. Additionally, FHND5032 reduces the expression of the M1 marker CD86 while increasing the M2 marker CD206 in RAW 264.7 cells. It also promotes the expression of barrier-sealing proteins ZO-1 and occludin in Caco-2 cells to enhance tight junction (TJ) assembly.

FHND5032 (25-50 mg/kg, administered orally once daily for 12 consecutive days) mitigates colitis and reduces inflammatory burden in a mouse model of ulcerative colitis induced by Dextran sulfate sodium salt (DSS).