Background Diarrhea-predominant irritable bowel syndrome (IBS-D) is a common functional gastrointestinal disease. Buzhong Yiqi Decoction combined with Fuzi Lizhong Decoction (BZFZ) has been clinically prescribed for IBS-D treatment. However, the precise mode of action and active components have not yet been elucidated. Objectives This study aims to assess the ability of BZFZ to treat IBS-D and to elucidate the underlying mechanism. Methods First, the identification of the active components and targets among BZFZ, IBS-D, and neuroprotection was performed through network pharmacology, network construction, Venn analysis, bioinformatics, machine learning, and molecular docking. Next, an IBS-D rat model was constructed to investigated the role of BZFZ in vivo . Moreover, the effects of BZFZ were assessed based on the fecal output, fecal water content (FWC), abdominal withdrawal reflex (AWR), and sucrose preference test. The factors that regulated the BZFZ effects on IBS-D were estimated using ELISA, western blot, and immunohistochemistry. Results Four targets (MET, RAP1A, IRAK1, and AGTR1) related to the neuroprotection effect of BZFZ in IBS-D patients were identified. BZFZ treatment significantly improved diarrhea, visceral sensitivity, depressive behavior, and intestinal permeability induced by IBS-D by increasing the abundance of intestinal tight junctions, decreasing the levels of pro-inflammatory cytokines (all P < 0.05). The expression of IRAK1 was upregulated in IBS-D rats, accompanied by elevated P-JNK, P-ERK, and P-P38 within the MAPK signaling pathway (all P < 0.05). BZFZ treatment decreased IRAK1 levels and inhibited the MAPK signaling pathway (all P < 0.05). Conclusions These results demonstrated that BZFZ alleviated depression and intestinal symptoms and restored the intestinal barrier function of IBS-D, accompanied with inhibition of the IRAK1/MAPK signaling pathway, offering significant insights into the potential molecular mechanisms of BZFZ.
Zhao et al. (Mon,) studied this question.