Polysaccharides from Elsholtzia rugulosa: structural characteristics and treating functional dyspepsia via gut microbiome in conjunction with targeting the PI3K/Akt/cGMP-PKG pathways.

BACKGROUND: Functional dyspepsia (FD) is a common gastrointestinal disorder characterized by symptoms such as epigastric pain, bloating, and nausea. Current treatments have limited efficacy and significant side effects. Elsholtzia rugulosa, a traditional medicinal plant, is used to treat gastrointestinal disorders, and its polysaccharides (ERP) may offer therapeutic potential for FD. OBJECTIVE: This study aimed to characterize the structural properties of Elsholtzia rugulosa polysaccharides (ERP) and explore their mechanism in treating FD. MATERIALS AND METHODS: Neutral ERP-N and acidic ERP-A were isolated from Elsholtzia rugulosa. Their structural features were analyzed, and FD rats were treated with ERP. Gastric pathology, gut microbiota, and the PI3K/Akt/cGMP-PKG pathway were evaluated. RAW264.7 cells were used to assess ERP's immunomodulatory effects. RESULTS: Structural Analysis: ERP-N (13,415 Da) and ERP-A (3,691 Da) exhibited distinct monosaccharide compositions and linkages. Therapeutic Effects: ERP improved FD symptoms, reduced inflammation, regulated gut microbiota, and activated the PI3K/Akt/cGMP-PKG pathway in rats. Immunomodulatory Activity: ERP-N promoted the secretion of nitric oxide (NO), TNF-α, and IL-6 in RAW264.7 cells, demonstrating immunomodulatory effects. CONCLUSION: ERP may alleviate FD in association with gut microbiota modulation and changes in the PI3K/Akt/cGMP-PKG-related pathway. ERP-N also exhibits immunomodulatory activity, supporting the traditional use of Elsholtzia rugulosa in gastrointestinal health and offering potential for FD therapy development.