[Research progress in mechanism of action and clinical translation of berberine in treatment of ulcerative colitis].

Ulcerative colitis(UC) is a chronic, idiopathic, and non-specific inflammatory bowel disease whose pathogenesis is intimately linked to the multifaceted dysregulation involving aberrant activation of the intestinal mucosal immune system, compromised intestinal epithelial barrier function, disruption of gut microbiota homeostasis, and oxidative stress. First-line clinical therapeutics, such as aminosalicylates, are often constrained by limited efficacy and risks of adverse effects. In contrast, berberine, an isoquinoline alkaloid derived from Coptidis Rhizoma, has emerged as a promising agent for UC treatment due to its potent anti-inflammatory and intestinal protective properties. This review systematically elaborates on the core mechanisms of berberine against UC, encompassing the suppression of intestinal hyperinflammation primarily through the modulation of the nuclear factor-κB(NF-κB) and mitogen-activated protein kinase(MAPK) signaling cascades, the enhancement of epithelial barrier repair via the activation of the aryl hydrocarbon receptor(AHR) and the Wnt/β-catenin pathway, the restoration of gut microbiota structure and associated metabolite profiles to re-establish structural and metabolic homeostasis, the remodeling of immune cell function through the regulation of specific immune cell subsets, and the amelioration of oxidative stress along with mitochondrial protection, mediated chiefly by the nuclear factor erythroid 2-related factor 2(Nrf2) pathway. Furthermore, berberine exerts regulatory effects on apoptosis, autophagy, and the activation of intestinal stem cells. Accumulating evidence suggests that berberine can improve clinical activity indices and mucosal healing in UC patients. Nevertheless, several challenges hinder its clinical translation, including low oral bioavailability, the absence of a standardized dosing protocol, and unelucidated risks associated with long-term administration. The development of colon-targeted delivery systems or nano-formulations offers a viable strategy to enhance the site-specific accumulation of berberine. Future investigations should prioritize the exploration of berberine-based combined therapies and precision medicine approaches to overcome existing clinical barriers and advance novel therapeutic paradigms for UC.