[Mechanism of Shengqing Jiangzhuo Granules in ameliorating chronic functional constipation with dampness obstruction and Qi stagnation pattern and associated hyperuricemia based on "gut-microbiota-barrier" axis].

This study systematically investigated the efficacy and action mechanism of Shengqing Jiangzhuo Granules in ameliorating chronic functional constipation with dampness obstruction and Qi stagnation pattern and associated hyperuricemia by integrating pharmacodynamic evaluation for animals, multi-omics detection, and mechanistic validation. First, a rat model of chronic functional constipation with dampness obstruction and Qi stagnation pattern associated hyperuricemia was established by using a multi-factor modeling method. Animals were divided into a normal group, a model group, Shengqing Jiangzhuo Granules groups with low, medium, and high doses, linagliptin group, and prucalopride succinate group. Intestinal propulsion rate, histopathological changes, serum gastrointestinal hormones [substance P(SP), motilin(MTL), vasoactive intestinal peptide(VIP)], uric acid, and lipid metabolism indicators [total cholesterol(TC), triglycerides(TG)], were detected to comprehensively evaluate the efficacy. Subsequently, 16S rDNA sequencing and colonic content metabolomic analysis were performed to delineate changes in gut microbiota structure and metabolite profiles. Through multi-omics correlation analysis, the key regulatory pathways were identified. Finally, the hypoxia-inducible factor-1α(HIF-1α) protein and the distribution/expression of zonula occludens-1(ZO-1) and occludin in colon tissue were detected to verify the relevant mechanism. The results demonstrate that Shengqing Jiangzhuo Granules significantly improve intestinal propulsion of the model rat, repair tissue damage in the colon, spleen, and stomach, regulate gastrointestinal hormone disturbances, reduce uric acid in the serum, and correct lipid metabolism disorders. Moreover, the prescription can reverse gut microbiota dysbiosis, promote the proliferation of butyrate-producing microbiota(e.g., Faecalibacterium and Blautia), increase colonic butyrate content, activate the HIF-1α signaling pathway, and enhance the expression of tight junction proteins. In conclusion, this study gradually delves from holistic pharmacodynamics to microscopic mechanism, clarifying that the action mechanism of Shengqing Jiangzhuo Granules in exerting a multi-target and holistic improvement effect on chronic functional constipation with dampness obstruction and Qi stagnation pattern, as well as its associated hyperuricemia through regulating the "gut microbiota-butyrate-HIF-1α-intestinal barrier" axis, providing a scientific basis for its clinical popularization and application.