Chu Fei, Chen Xiaohua, Song Bowen, Yang Jingjing, Zuo Lugen
Department of Pharmacy, Bengbu 233030, China.
Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical University, Bengbu 233004, China, Bengbu 233030, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2025 Apr 20;45(4):819-828. doi: 10.12122/j.issn.1673-4254.2025.04.17.
To investigate the effect of moslosooflavone (MOS) for ameliorating dextran sulfate sodium (DSS)-induced colitis in mice and the underlying molecular mechanism.
C57BL/6J mice with or without DSS exposure in the drinking water were both randomized into two groups for treatment with intraperitoneal injections with MOS (200 mg/kg) or normal saline for 7 days (=6). Disease severity of the mice was assessed by observing changes in body weight, colon length, histopathology (HE staining), intestinal barrier function, and TUNEL staining. In the studies, lipopolysaccharide (LPS)-stimulated mouse colon organoids were treated with MOS (120 μmol/L) for 24 h, and the changes in barrier dysfunction and inflammation were analyzed. Network pharmacology and Western blotting were employed to identify functional pathways and apoptotic protein regulation associated with the therapeutic effect of MOS on colitis.
In the mouse models of DSS-indcued colitis, MOS treatment significantly reduced body weight loss, disease activity index (DAI) scores and colon shortening, ameliorated colonic histopathological changes and inflammation, and lowered pro-inflammatory cytokine levels (TNF-α, IL-1β, IL-6, and IFN-γ). MOS effectively restored intestinal barrier integrity in the mice by reducing serum FITC-dextran and I-FABP concentrations while enhancing the tight junction proteins (ZO-1 and claudin-1). In the colon organoids, MOS significantly suppressed LPS-induced inflammatory responses and epithelial barrier disruption. Western blotting revealed that MOS downregulated C-caspase-3 and BAX and upregulated Bcl-2 expressions in both models. Mechanistically, MOS suppressed PI3K and AKT phosphorylation in both DSS-treated mouse colonic tissues and LPS-stimulated organoids.
MOS alleviates experimental colitis in mice by inhibiting intestinal epithelial apoptosis via inhibiting the PI3K/AKT pathway, thereby restoring intestinal barrier integrity and reducing inflammation.
研究莫索黄酮（MOS）对改善葡聚糖硫酸钠（DSS）诱导的小鼠结肠炎的作用及其潜在分子机制。
将饮用含或不含DSS的水的C57BL/6J小鼠随机分为两组，腹腔注射MOS（200mg/kg）或生理盐水，连续7天（每组n = 6）。通过观察体重变化、结肠长度、组织病理学（苏木精-伊红染色）、肠道屏障功能和TUNEL染色来评估小鼠的疾病严重程度。在体外研究中，用MOS（120μmol/L）处理脂多糖（LPS）刺激的小鼠结肠类器官24小时，并分析屏障功能障碍和炎症的变化。采用网络药理学和蛋白质免疫印迹法来确定与MOS对结肠炎治疗作用相关的功能途径和凋亡蛋白调控。
在DSS诱导的结肠炎小鼠模型中，MOS治疗显著减轻体重减轻、疾病活动指数（DAI）评分和结肠缩短，改善结肠组织病理学变化和炎症，并降低促炎细胞因子水平（TNF-α、IL-1β、IL-6和IFN-γ）。MOS通过降低血清异硫氰酸荧光素-葡聚糖和肠脂肪酸结合蛋白浓度，同时增强紧密连接蛋白（ZO-1和闭合蛋白-1），有效恢复了小鼠肠道屏障的完整性。在结肠类器官中，MOS显著抑制LPS诱导的炎症反应和上皮屏障破坏。蛋白质免疫印迹显示，在两个模型中MOS均下调了C-半胱天冬酶-3和BAX的表达，并上调了Bcl-2的表达。机制上，MOS在DSS处理的小鼠结肠组织和LPS刺激的类器官中均抑制了PI3K和AKT的磷酸化。
MOS通过抑制PI3K/AKT途径抑制肠上皮细胞凋亡，从而恢复肠道屏障完整性并减轻炎症，进而缓解小鼠实验性结肠炎。
