Three bioactive compounds from Huangqin decoction ameliorate Irinotecan-induced diarrhea via dual-targeting of Escherichia coli and bacterial β-glucuronidase

• DOI: 10.1007/s10565-024-09922-0
• Publication Date: 2024-10-18T08:02:38Z
• Authors: Xiaojun Teng; Bingxin Wu; Zuhui Liang; Lisheng Zhang; Maolin Yang; Zhongqiu Liu; Qi Liang; Caiyan Wang
• Keywords: Decoction

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