Aloe-emodin regulates colon epithelial cell function by regulating HIF-1α to alleviate irritable bowel syndrome

This study aimed to investigate the therapeutic potential of Aloe-emodin (AE) for irritable bowel syndrome (IBS), focusing on its effects and underlying mechanisms.Deoxycholic acid (DCA)-induced IBS rats (Sprague-Dawley) were orally administered AE. Body weight and faecal pellet were monitored. Anxiety-like behaviour, visceral hypersensitivity, colon permeability were assessed via the open-field (OF) test, abdominal Withdrawal Reflex (AWR) score, FITC-dextran fluorescence, respectively. Enzyme-linked immunosorbent assay (ELISA) quantified substance P (SP), 5-hydroxytryptamine (5-HT), TNF-α, and IL-6 levels. Hypoxia inducible factor-1α (HIF-1α) expression was analysed via qRT-PCR. The mechanism of AE on IBS was evaluated in LPS-treated NCM460 injury.AE alleviated IBS symptoms (improved weight gain, reduced faecal output/water content, increased centre exploration time, lowered AWR scores, decreased colon permeability, SP, 5-HT, and pro-inflammatory cytokine levels). HIF-1α upregulation in colonic tissues and LPS-induced NCM460 cells was suppressed by AE treatment. The protective effect of AE was reversed by HIF-1α overexpression in IBS rats. AE enhanced cell proliferation, reduced cellular permeability, and inflammation in LPS-stimulated NCM460 cells. HIF-1α overexpression partially reversed the protective effects of AE in LPS-induced NCM460 injury.AE ameliorated IBS symptoms by promoting cell proliferation, suppressing cell permeability, and inflammation of colonic epithelial cells via regulating HIF-1α.