Zhang Yuansen, Jin Xiaosheng, Xia Huanhuan, Wu Xiaoqiu, Chen Wenjun, Zhuang Mengxiao, Tang Sensen
Department of Gastroenterology, The Third Affiliated Hospital of Wenzhou Medical University, Ruian, Zhejiang, China.
Department of Pharmacy, The Third Affiliated Hospital of Wenzhou Medical University, Ruian, Zhejiang, China.
J Biochem Mol Toxicol. 2025 Jun;39(6):e70287. doi: 10.1002/jbt.70287.
Ulcerative colitis (UC), a common inflammatory bowel disease, has become increasingly prevalent worldwide, posing significant health challenges. This study explored the anti-inflammatory effects of β-sitosterol on UC and its underlying molecular mechanisms. Using a dextran sulfate sodium (DSS)-induced colitis model in male C57BL/6 mice, the therapeutic potential of β-sitosterol at low (2 mg/kg) and high (6 mg/kg) doses was compared with sulfasalazine (300 mg/kg) as a positive control. Disease progression was assessed through Disease Activity Index (DAI) scores, histological analysis, and inflammatory marker expression. β-sitosterol significantly ameliorated colonic inflammation, demonstrated by lower DAI scores, improved histological architecture, and reduced levels of inflammatory mediators, including NO, MPO, IL-6, and iNOS, while upregulating the anti-inflammatory cytokine IL-10. Mechanistically, β-sitosterol promoted AMP-activated protein kinase (AMPK) expression and suppressed myosin light chain kinase (MLCK) expression. These findings were validated in vitro using LPS-stimulated Caco-2 cells, where β-sitosterol decreased inflammatory marker levels and modulated AMPK/MLCK signaling. Notably, the use of Compound C, an AMPK inhibitor, reversed these effects by suppressing AMPK activity and restoring MLCK expression, confirming that the anti-inflammatory actions of β-sitosterol are AMPK-dependent. In conclusion, this study highlights the therapeutic potential of β-sitosterol in UC through modulation of the AMPK/MLCK signaling pathway. These findings not only deepen our understanding of β-sitosterol's anti-inflammatory properties but also suggest its potential in developing novel AMPK-targeted therapies for inflammatory bowel disease management.
溃疡性结肠炎（UC）是一种常见的炎症性肠病，在全球范围内日益普遍，带来了重大的健康挑战。本研究探讨了β-谷甾醇对UC的抗炎作用及其潜在的分子机制。在雄性C57BL/6小鼠中使用葡聚糖硫酸钠（DSS）诱导的结肠炎模型，将低剂量（2mg/kg）和高剂量（6mg/kg）的β-谷甾醇的治疗潜力与作为阳性对照的柳氮磺胺吡啶（300mg/kg）进行比较。通过疾病活动指数（DAI）评分、组织学分析和炎症标志物表达来评估疾病进展。β-谷甾醇显著改善了结肠炎症，表现为较低的DAI评分、改善的组织结构以及包括NO、MPO、IL-6和iNOS在内的炎症介质水平降低，同时上调抗炎细胞因子IL-10。机制上，β-谷甾醇促进AMP激活的蛋白激酶（AMPK）表达并抑制肌球蛋白轻链激酶（MLCK）表达。这些发现使用LPS刺激的Caco-2细胞在体外得到验证，其中β-谷甾醇降低了炎症标志物水平并调节了AMPK/MLCK信号通路。值得注意的是，使用AMPK抑制剂Compound C通过抑制AMPK活性和恢复MLCK表达逆转了这些作用，证实β-谷甾醇的抗炎作用是AMPK依赖性的。总之，本研究强调了β-谷甾醇通过调节AMPK/MLCK信号通路在UC中的治疗潜力。这些发现不仅加深了我们对β-谷甾醇抗炎特性的理解，还表明其在开发针对炎症性肠病管理的新型AMPK靶向疗法方面的潜力。
