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Tongfei Feng1,2,3, Yanlin Zhou1,3, Bin Lv1,3
1Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310003, People's Republic of China.
xiayaofang (TXYF) 通过调节乙胆 (Ach) 和CHRM3通路来治疗易怒肠综合征 (IBS),保护肠道屏障. 这项研究揭示了TXYFF.
科学领域:
- 药理学和中国传统医学
- 胃肠病学 胃肠病学
- 分子生物学分子生物学
背景情况:
- 刺激性肠综合征 (IBS) 是一种普遍存在的胃肠疾病,具有复杂的,往往不清楚的分子基础.
- xiayaofeng (TXYF) 是一种用于治疗IBS的传统中医配方,但其精确的分子机制在很大程度上仍未被探索.
- 了解TXYF调节的特定目标和途径对于其合理的临床应用和潜在的药物开发至关重要.
研究的目的:
- 用综合网络药理学,分子对接和体内验证方法阐明Tongxieyaofeng (TXYF) 在治疗生气性肠综合征 (IBS) 中的分子机制.
- 研究CHRM3和肠道屏障在TXYF对IBS的治疗作用中的特定作用.
- 为了确定TXYF的关键活性成分和分子标,与IBS治疗相关.
主要方法:
- 网络药理学与TCMSP,基因卡和OMIM数据库相结合,以识别TXYF活性成分和IBS目标.
- 分子对接以验证TXYF组件与已确定目标的结合亲和力,包括CHRM3.
- 使用压力诱导的IBS模型进行体内验证,评估CHRM3表达,肠壁完整性,炎症标志物和相关信号通路 (GNAQ/PLC/MLCK,NF-κB/MLCK).
主要成果:
- LC-MS在TXYF中发现了559个组件,其中23个被认为是有效的. 凯格 (KEGG) 的分析强调了的作用. 纳灵宁和诺比莱丁显示强烈结合CHRM3.
- 在体内研究证实,TXYF在IBS模型中抑制了乙胆 (Ach) 和CHRM3激活,调节了GNAQ/PLC/MLCK轴.
- 通过降低TNF-α,MMP9和NF-κB/MLCK通路的调节,以及调节杯状细胞分泌,TXYF对肠道屏障产生保护作用.
结论:
- xiayaofeng (TXYF) 通过抑制乙胆 (Ach) 和CHRM3表达来缓解IBS症状,从而通过GNAQ/PLC/MLCK通路调节肠道光滑肌肉放松.
- TXYF通过抑制NF-κB/MLCK激活和调节杯状细胞分泌来保护肠道屏障功能.
- 这项研究为TXYF在治疗IBS中的有效性提供了全面的分子基础,强调CHRM3和肠道屏障调节是关键机制.
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