Baitouweng Decoction is a famous Chinese medicinal decoction that has been used to treat diarrhea over thousands of years. In this study, we investigated the effect and mechanism of Baitouweng Decoction in the treatment of diarrhea. Wistar rats were randomly assigned into 4 groups: control group, dampness-heat diarrhea model group(modeling by complex factors including high-sugar and high-fat diet, improper diet, hot and humid environment, drinking and intraperitoneal injection of Escherichia coli), Baitouweng Decoction(3.6 g·kg~(-1)) group, and self-healing group. A urine metabolomics approach was developed with ultra liquid chromatography-quadrupole-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS) for metabolic profiling. The differential metabolites were screened out by the multivariate comparison between groups. Diarrhea-related protein targets and the active compounds of Baitouweng Decoction were used to predict the protein targets of Baitouweng Decoction. Cytoscape 3.2.1 was employed to establish a active component-target protein interaction network. Three protein-protein interaction(PPI) networks of component target proteins, diarrhea-related proteins, and differential metabolite-related proteins were established and then merged by BisoGenet. ClueGO was used to perform the gene enrichment based on the genetic similarity. The results showed that Baitouweng Decoction effectively treated dampness-heat diarrhea in vivo. N-acetylserotonin, L-gamma-glutamylcysteine, glutathione, retinoate, melatonin, indole-3-acetaldehyde, L-cystine, biotin, and L-tryptophan were screened as differential metabolites in dampness-heat diarrhea model group. Tryptophan metabolism, glutathione metabolism, biotin metabolism, retinol metabolism, and cysteine and methionine metabolism were involved in the therapeutic effect of Baitouweng Decoction in vivo. A total of 167 targets were identified as major candidates for diarrhea progression. The gene-set enrichment revealed that the targets were involved in reactive oxygen species production, inflammation, and apoptosis. Baitouweng Decoction can restrain inflammation, production of reactive oxygen, and block apoptosis, thereby contributing to the treatment of dampness-heat diarrhea.
Keywords: Baitouweng Decoction; dampness-heat diarrhea; metabolomics; network pharmacology.