Introduction and objective:
Diarrhea with syndrome of spleen deficiency with dampness encumbrance (D-SSDDE) is a clinically debilitating condition, and the therapeutic mechanisms of Xiangsha Weiling Pills (XsWlP) against it remain unclear. The aim of the study is to explore the multidimensional regulatory mechanisms of XsWlP on D-SSDDE, and predict the key targets of its therapeutic effects using network pharmacology.

Material and methods:
In the D-SSDDE mouse model, physiological disorders were assessed by measuring loose stool rates and abdominal temperature, and using enzyme-linked immunosorbent assay (ELISA) to measure serum triglyceride (TG) levels. Gut barrier function was assessed by detecting goblet cell proportions using flow cytometry and quantifying tight junction protein (ZO-1, Claudin-1, MUC2) expression levels via reverse transcription quantitative polymerase chain reaction (RT-qPCR). The potential targets of XsWlP were predicted using network pharmacology. Additionally, we quantified interleukin 6 (IL6) and transforming growth factor beta 1 (TGFB1) expression levels in mouse intestinal tissues and serum via RT-qPCR and ELISA.

Results:
XsWlP substantially reverses D-SSDDE-induced metabolic disruptions, including reduced loose stool rate, restored abdominal temperature, and normalized serum TG levels, while repairing gut barrier integrity by adjusting goblet cell ratio and inducing tight junction proteins. Molecular docking validates TGFB1 and IL6 binding affinity. Moreover, XsWlP markedly suppresses the aberrant expression of D-SSDDE-induced pro-inflammatory factors, such as IL-6 and TGF-β1.

Conclusions:
The study demonstrates that XsWlP reduces intestinal barrier disruption in D-SSDDE via TGFB1/IL-6 signaling.