Effects of Shenling Baizhu Powder on Pyrotinib-Induced Diarrhea: Analysis of Gut Microbiota, Metabonomics, and Network Pharmacology

Abstract

Background Shenling Baizhu Powder (SBP) is a traditional Chinese medicine (TCM) prescription, which has good efficacy on gastrointestinal toxicity. In this study, we used gut microbiota analysis, metabonomics, and network pharmacology to investigate the therapeutic effect of SBP on pyrotinib-induced diarrhea. Methods 24 Rats were randomly divided into 4 groups: control group, SBP group (3.6 g/kg /bid SBP for 10 days), pyrotinib model group (80mg/kg/qd pyrotinib), and pyrotinib + SBP treatment group. A 16S rRNA sequencing was used to detect the microbiome of rat fecal bowel, metabolic profiles were collected by non-targeted metabolomics, and key metabolic pathways were identified using MetaboAnalyst 5.0. The antitumor effect of SBP on cells treated with pyrotinib was measured using a CCK-8 assay. Network pharmacology was used to predict the target and action pathway of SBP in treating pyrotinib-related diarrhea. Results In vivo study indicated that SBP could significantly alleviate pyrotinib-induced diarrhea, reaching a therapeutic effect of 66.7%. SBP could regulate pyrotinib-induced microbiota disorder. LEfSe research revealed that the SBP could potentially decrease the relative abundance of Escherichia, Helicobacter, and Enterobacteriaceae and increase the relative abundance of Lachnospiraceae, Bacilli, Lactobacillales etc. In addition, 25-Hydroxycholesterol, Guanidinosuccinic acid, 5-Hydroxyindolepyruvate, and cAMP were selected as potential biomarkers of SBP for pyrotinib-induced diarrhea. Moreover, Spearman's analysis showed a correlation between gut microbiota and metabolite: the decreased 25-hydroxycholesterol in the SBP treatment group was negatively correlated with Lachnospiraceae while positively correlated with Escherichia and Helicobacter. Meanwhile, SBP did not affect the inhibitory effect of pyrotinib on BT-474 cells and Calu-3 cells in vitro. Also, network analysis further revealed that SBP treated pyrotinib-induced diarrhea through multiple pathways, including inflammatory bowel disease, IL-17 signaling pathway, pathogenic Escherichia coli infection, and cAMP signaling pathway. Conclusions SBP could effectively relieve pyrotinib-induced diarrhea, revealing that intestinal flora and its metabolites may be involved in this process.

Research Progress of Traditional Chinese Treatment of Diabetic Diarrhea

“…This suggests that Shen Ling Baizhu San can improve diabetic diarrhea symptoms and gastrointestinal hormones. Yang Li [25] selected 60 cases of diabetic diarrhea (spleen and stomach weakness type) patients, control group and observation group randomly 30 cases each, the control group was given pinaverium Bromide, the observation group in the control group on the basis of Shen Ling Baizhu San, the results suggest that the observation group's total effective rate, immunoglobulin level is higher than that of the control group, and the points of Chinese medicine symptoms, recurrence rate is lower than that of the control group. This suggests that Shen Ling Baizhu San has a certain role in the treatment of diabetic diarrhea.…”