[Efficacy comparison of Atractylodis Macrocephalae Rhizoma with different growth years in treatment of slow transit constipation and its mechanism].

This study investigated the efficacy differences of Atractylodis Macrocephalae Rhizoma with different growth years in treating slow transit constipation(STC) and explored its potential mechanism of action. Thirty-six male KM mice were randomly assigned to six groups(n=6): blank control group, STC model group, two-year Atractylodis Macrocephalae Rhizoma group, four-year Atractylodis Macrocephalae Rhizoma group, ten-year Atractylodis Macrocephalae Rhizoma group, and mosapride group. The STC model was established via loperamide hydrochloride suspension gavage. Efficacy indicators including defecation function, intestinal transit rate, histopathology, and serum levels of gastrointestinal hormones were measured to evaluate the effectiveness of Atractylodis Macrocephalae Rhizoma with different growth years in improving STC. Untargeted metabolomics was used to analyze differential metabolites in mouse feces, and related metabolic pathways were enriched. Immunohistochemistry and Western blot(WB) were used to verify the proteins related to the key pathways. In comparison to the model group, all Atractylodis Macrocephalae Rhizoma-treated groups significantly alleviated STC symptoms to varying degrees. Notably, the ten-year Atractylodis Macrocephalae Rhizoma group demonstrated the most pronounced ameliorative effects: defecation function and intestinal transit rate were significantly enhanced; histopathological damage in colon tissue was reduced; serum levels of motilin(MTL) and gastrin(GAS) were markedly increased; the level of total bile acids(TBA) in the colon decreased. A total of 45 differential metabolites were identified in metabonomics study, of which 20 had a pullback after the ten-year Atractylodis Macrocephalae Rhizoma intervention. Pathway enrichment analysis revealed that the differential metabolites primarily involved primary bile acid biosynthesis, biosynthesis of phenylalanine, tyrosine, and tryptophan, and phenylalanine metabolism. Immunohistochemistry and WB results showed that ten-year Atractylodis Macrocephalae Rhizoma influenced bile acid metabolism probably by modulating the farnesoid X receptor(FXR) and G protein-coupled bile acid receptor 5(TGR5), thereby restoring the intestinal mucosal barrier(upregulating the expression of occludin and claudin-1). This study provides an experimental foundation for further clarifying the effectiveness of genuine Atractylodis Macrocephalae Rhizoma in treating STC.