Jiawei YigongSan improves gastric motility and is associated with modulation of PI3K/Akt/mTOR signaling and autophagy in a rat model of functional dyspepsia.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiawei YigongSan (JWYGS), a modified traditional Chinese medicine formula derived from Yigong San, is traditionally used to tonify Qi, strengthen the spleen, and regulate gastrointestinal function. However, its potential mechanisms in functional dyspepsia (FD) remain insufficiently clarified.

AIM OF THE STUDY: This study aimed to investigate the effects of JWYGS on gastric motility dysfunction in a rat model of FD and to explore its potential association with interstitial cells of Cajal (ICCs), autophagy-related protein regulation, and the PI3K/Akt/mTOR signaling pathway.

MATERIALS AND

METHODS

A composite FD rat model was established using irregular feeding, fatigue stimulation, and senna administration. Gastric emptying and intestinal transit were evaluated. Serum levels of motilin and gastrin were measured. ICC-associated markers (C-kit and ANO1) were assessed by immunohistochemistry. Autophagy-related proteins (Beclin-1, LC3B, p62) and PI3K/Akt/mTOR pathway components, including phosphorylated forms, were analyzed by Western blot. LC-MS profiling and network pharmacology analysis were performed to characterize major constituents and predict potential signaling pathways. Serum biochemical indices were examined to evaluate safety.

RESULTS

FD model rats exhibited delayed gastric emptying, reduced intestinal transit, decreased pro-motility hormone levels, diminished expression of ICC-related markers, altered autophagy-related protein profiles, and increased activation of the PI3K/Akt/mTOR pathway. JWYGS treatment was associated with improvements in gastric motility parameters, normalization of motilin and gastrin levels, enhanced expression of C-kit and ANO1, reversal of autophagy-related protein alterations, and reduced phosphorylation of Akt, mTOR, and S6K. Network pharmacology analysis indicated enrichment of targets within the PI3K-Akt signaling pathway, consistent with experimental observations. No significant hepatotoxicity or nephrotoxicity was observed within the tested dosage range.

CONCLUSION

JWYGS administration was associated with improved gastrointestinal motility, preservation of ICC-related marker expression, and modulation of autophagy-related protein profiles and PI3K/Akt/mTOR signaling in FD rats. These findings provide experimental support for the traditional application of JWYGS and offer a foundation for further mechanistic investigation.