Therapeutic Effects of Shengdu Pingmu Formula on Loperamide-Induced Constipation in Rats via PI3K/AKT Signaling and Gut Microbiota Regulation.

Constipation is a common gastrointestinal disorder, and current treatments often have limitations. Shengdu Pingmu Formula (SDPF), a modified formulation derived from Traditional Chinese Medicine, has been used clinically to treat constipation, but its mechanism of action remains unclear. This study employed UPLC-Q/TOF-MS analysis to identify 188 compounds in SDPF, of which 50 were conclusively confirmed. In animal experiments, SDPF treatment significantly enhanced intestinal propulsion, increased fecal water content, and shortened the time to first black stool. Network pharmacology and molecular docking analyses suggested the involvement of the PI3K/AKT pathway, which was subsequently validated by observed upregulation of this pathway and increased expression of AQP3 and AQP8 in the rectum. Furthermore, 16S rRNA gene sequencing revealed that SDPF restored gut microbiota homeostasis by elevating beneficial bacteria such as Lactobacillus and Bacteroides while reducing bacteria associated with inflammation. Collectively, SDPF effectively alleviates constipation through mechanisms that regulate the PI3K/AKT pathway and modulate gut microbiota.