伊立替康 (CPT-11) 是一种治疗结肠癌的常用化疗药物。不幸的是，急性和迟发性腹泻是 CPT-11 使用的主要副作用，这限制了其治疗潜力。黄芩汤（HQD）对化疗引起的腹泻的疗效已被证实。本研究调查了 HQD 成分（黄芩素、黄芩苷和芍药苷）对 CPT-11 诱导的腹泻的功效及其潜在机制。通过肠道通透性测试、ELISA、荧光共定位和 IHC 发现黄芩素是改善 CPT-11 诱导的肠毒性最有效的成分。黄芩苷、黄芩苷与芍药苷合用，可获得与HQD相似的治疗效果。孟德尔随机分析、16 s rRNA 测序和荧光成像表明，黄芩素和黄芩苷显着抑制 β-葡萄糖醛酸酶 (β-GUS) 活性。细菌丰度分析和扫描电子显微镜表明，黄芩素通过破坏大肠杆菌的细胞壁来抑制其增殖。分子动力学和定点突变结果揭示了黄芩素和黄芩苷抑制β-GUS的结构基础。上述结果为辅助化疗药物治疗的发展提供了新的思路，也为β-GUS靶向分子结构的优化提供了理论指导。© 2024。作者。

Irinotecan (CPT-11) is a commonly prescribed chemotherapeutic for the treatment of colon cancer. Unfortunately, acute and delayed diarrhea are prominent side effects of CPT-11 use, and this limits its therapeutic potential. The curative effect of Huangqin decoction (HQD) on chemotherapy-induced diarrhea has been proven. This study investigated the efficacy of the components of HQD (baicalein, baicalin, and paeoniflorin) on CPT-11-induced diarrhea and their underlying mechanisms. Baicalein was found to be the most effective component in improving CPT-11-induced enterotoxicity by intestinal permeability test, ELISA, fluorescence co-localization, and IHC. The combination of baicalin, baicalin and paeoniflorin can obtain similar therapeutic effect to that of HQD. Mendelian randomization analysis, 16 s rRNA sequencing, and fluorescence imaging revealed that baicalein and baicalin significantly inhibited β-glucuronidase (β-GUS) activity. Bacterial abundance analysis and scanning electron microscopy showed that baicalein inhibited the proliferation of Escherichia coli by destroying its cell wall. The molecular dynamics and site-directed mutagenesis results revealed the structural basis for the inhibition of β-GUS by baicalein and baicalin. The results above provide a new idea for the development of drug therapy for adjuvant chemotherapy and theoretical guidance for the optimization of molecular structure targeting β-GUS.© 2024. The Author(s).