In China, Baitouweng Tang (BTWT) is a commonly prescribed remedy for the treatment of ulcerative colitis (UC). Herein, the present study aims to assess the anti-colitis activity of BTWT and its underlying mechanisms in UC BALB/c mice. Induction of UC in BALB/c mice was carried out by adding 3.5% DSS in the drinking water of underlined mice. After UC induction, the mice were administrated with BTWT for 7 days. Clinical symptoms were assessed, followed by analyzing the bile acids (BAs) in serum, liver, colon, bile, and feces of UC mice through UPLC-MS/MS. The modified 16S rDNA high-throughput sequencing was carried out to examine the gut microbiota of feces. BTWT significantly improved the clinical symptoms such as and histological injury and colon shortening in UC induced mice. Furthermore, BTWT remarkably ameliorated colonic inflammatory response. After BTWT treatment, the increased concentrations of UDCA, HDCA, αMCA, βMCA, CA, and GLCA in UC were decreased, and the levels of some BAs, especially CA, αMCA, and βMCA were normalized. Moreover, the relative species abundance and gut microbiota diversity in the BTWT-exposed groups were found to be considerably elevated than those in the DSS-treated group. BTWT increased the relative abundance of Firmicutes, Proteobacteria, Actinobacteria, Tenericutes, and TM7, which were statistically lower in the fecal microbiota of UC mice. The relative abundance of Bacteroidetes was found to be elevated in the DSS group and normalized after BTWT treatment. BTWT increased the expression of FXR and TGR5 in the liver. BTWT administration improved DSS-induced mice signs by increasing the TGR5 and FXR expression levels. This result was achieved by the regulation of the BAs and gut microbiota.

Ethnopharmacological Relevance: Diarrhea is a major medical problem in clinical practice. According to the theory of traditional Chinese medicine (TCM), different types of diarrhea should be treated with different TCM formulations based on the targeted medical condition. Dampness-heat diarrhea (DHD) is a serious diarrheal disease and Pulsatilla decoction (PD), a TCM, has been found effective against DHD. Objectiv: The aim of this study was to clarify the mechanism of action of PD in DHD using an untargeted lipidomics strategy. Materials and Methods: Wistar rats were randomized to four groups, including the control group, model group, PD groups and self-healing group. The PD groups were given a daily intragastric gavage of PD at doses of 3.76 g/kg. The rat model of DHD established by such complex factors as high-sugar and high-fat diet, improper diet, high temperature and humidity environment, drinking and intraperitoneal injection of Escherichia coli., which imitated the inducing conditions of DHD. Then the clinical symptoms and signs, blood routine, serum inflammatory cytokines levels and the histopathological changes of main organs were detected and observed to evaluate DHD model and therapeutic effect of PD. Lipid biomarkers of DHD were selected by comparing the control and model groups with the colon lipidomics technology and an ultra-high performance liquid chromatography (UHPLC) coupled with Q Exactive plus mass analyzer. Multivariate statistical analysis and pattern recognition were employed to examine different lipids within the colon of PD-treated rats. Results: The clinical symptoms and signs of the model rats were consistent with the diagnostic criteria of DHD. After treatment with PD, the clinical symptoms and signs of the rats with DHD were improved; the indexes of blood routine and inflammatory cytokines levels tended to be normal. The lipidomics profile of the model group were evidently disordered when compared to the control group. A total of 42 significantly altered lipids between the model-control groups were identified by multivariate statistical analysis. DHD may result from such lipid disorders which are related to glycerophospholipid metabolism, arachidonic acid (AA) metabolism, and sphingolipid metabolism. After PD treatment, the lipidomic profiles of the disorders tended to recover when compared to the model group. Twenty lipid molecules were identified and some glycerophospholipids and AA levels returned close to the normal level. Conclusion: Glycerophospholipid metabolism may play an important role in the treatment of dampness-heat induced diarrhea using PD.