Combination of polysaccharides from Astragalus membranaceus and Codonopsis pilosula ameliorated mice colitis and underlying mechanisms

Astragalus membranaceus and Codonopsis pilosula which are two Chinese medicinal herbs are often combinedly used as monarch drugs in Traditional Chinese Medicine (TCM) prescriptions to treat ulcerative colitis (UC). However, the exact mechanisms and effective constituents of the two herbs remain unclear. Polysaccharides are the main active ingredients of the two medicinal herbs and some specific polysaccharides extracted from the two medicinal herbs have been proven effective in relieving colitis. Hence, we speculated that polysaccharides of the two medicinal herbs may be the material basis for compatibility in TCM prescriptions to treat UC. In the research, total polysaccharides of A. membranaceus and C. pilosula extractum, named AERP and CERP respectively, were administrated to 2.5% dextran sulfate sodium (DSS)-induced acute colitis mice by dosing alone and in combination to test this hypothesis. 5-aminosalicylic acid (5-ASA, 100 mg/kg/d) was selected as the positive drug. The basic indexes of colitis mice including body weight, stool bleeding, stool consistency and colon lengths were recorded. In addition, tissue inflammatory factors, mucosa-associated proteins, fecal short chain fatty acids (SCFAs) and gut microbiota were also analyzed. The co-administration of AERP and CERP at specific doses could improve the clinical symptoms, reestablish the immune balance, and alleviate colonic mucosal injury in colitis mice. The unique efficacy of co-administration relied on activation of the aryl hydrocarbon receptor (AhR) and up-regulation of isovaleric acid and butyrate. In addition, the structure of intestinal flora was recovered in the co-administration group. Our research proved the efficacy after co-administration of total polysaccharides from A. membranaceus and C. pilosula on colitis mice which provided a theoretical basis for their compatibility in TCM prescriptions to treat UC.