Jiao San Xian granule containing prebiotic alleviate functional dyspepsia by regulating intestinal flora and the secretion of inflammatory response

Huimin Pei ^a,1, Mengyuan Zhao ^a,1, Hongyue Wang^a, Xindi Zhang ^b,c, Caihong Shi ^a, Xiangrong Zhang ^a,*

^a Faculty of Functional Food and Wine, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China

^b Food Processing Institute, Heilongjiang Academy of Agricultural Sciences, 368 Xuefu Road, Harbin 150086, China

^c Key Laboratory of Food Processing of Heilongjiang Province, Harbin 150086, China

Jiao Sanxian (JSX) consists of three traditional Chinese medicine including charred hawthorn, malt and Liu Shen Qu, they are also from Chinese medicine homologous food. It is commonly used to relieve functional dyspepsia (FD). The present study aims to explore the mechanism of JSX (granule), with the addition of prebiotics for the treatment of FD using mice model. The network pharmacology and molecular docking were used to forecast therapeutic targets for JSX. Based on the protein-protein interaction (PPI) results, thirteen targets exhibited strong interactions with each other. The results of network pharmacology and molecular docking revealed therapeutic activity of JSX in FD regulated by its anti-inflammatory effect, improvement in gastrointestinal function and physiological activity in components-targets-pathways-disease. The pharmacological effects of JSX were further verified by rRNA gene sequencing, enzyme-linked immunosorbent assay (ELISA) and animal study. The in vivo results showed JSX, in combination with prebiotics, could mitigate FD symptoms. ELISA study showed that glyceraldehyde-3-phosphate dehydrogenase (GAPDH), AKT1 and tumor necrosis factor (TNF) -α played the roles in reducing the inflammatory response by downregulating inflammation content. The above results were coincided with the network pharmacology prediction. By 16S rRNA, the results showed JSX may alleviate the FD symptom by increasing the diversity of the intestinal flora, adjusting the dominant prebiotic. In conclusion, JSX can alleviate functional dyspepsia in mice. The mechanisms were related to regulating the secretion of inflammatory response, significantly improving the benefits of intestinal flora and ameliorating multi-metabolic pathways.