Effects And Mechanism On Anti-inflammatory Bowel Disease Of Panax Notoginseng Saponins Mediated By Gut Microbiota

Background:Inflammatory bowel disease(IBD)is an idiopathic intestinal inflammatory disease,and long-term drug treatment is often accompanied by side effects,so it is particularly important to find safe and effective drugs to treat IBD.Gut microbiota are closely related to the occurrence and development of IBD.Drugs can regulate the structure and function of gut microbiota,and gut microbiota can also transform and metabolize drugs to affect their bioavailability and activity.Traditional Chinese medicine has the advantages of treating chronic and refractory diseases,and most of them are taken orally and in close contact with the gut microbiota.Panax notoginseng saponins(PNS)have been confirmed to interact with gut microbiota and can be used in the treatment of IBD.However,there is no research report on the role of gut microbiota in PNS exerting anti-IBD drugs.Objective:The aim of this study was to investigate the role of gut microbiota in the treatment of IBD with PNS.Methods : In this study,Animal experiments were divided into control group,model group,low-dose Panax notoginseng saponin group(20mg/kg),high-dose Panax notoginseng saponin group(60mg/kg)and positive control mesalazine group.DSS was used to construct a chronic ulcerative colitis model,and the efficacy of PNS anti-colitis was evaluated by HE staining,colon length measurement,body weight analysis,and detection of inflammatory factor levels.Flow cytometry was used to detect the number of Th17 or Treg cells in the mouse spleen and blood,FITC-dextran was used to detect the intestinal barrier,and16 s RNA amplicon sequencing was used to analyze the structure of the gut microbiota.Through in vitro co-incubation and determination of bacterial growth curve to further verify the regulation of PNS and its gut microbiota-metabolites on gut microbiota.The fecal microbiota transplantation experiment verified that the anti-colitis efficacy of PNS is related to its regulation of gut microbiota.And the biological functions of the main different bacterial species are studied in vitro.Finally,the anticolitis efficacy of the gut microbiota metabolite GC-K of PNS was evaluated in vivo.Result:In this study,we found that PNS can significantly alleviate the symptoms of colitis,reduce the DAI score and the level of inflammatory factors,and improve the intestinal barrier.The 16 s RNA sequencing results of mouse feces showed that Bacteroides was significantly increased after modeling with DSS,while PNS could reduce its abundance and significantly increase the abundance of Akkermansia.In vitro incubation results showed that PNS had no obvious effect on Akkermansia and Bacteroides,but GC-K,its metabolites produced by gut microbiota,had inhibitory effects on B.thetaiotaomicron and B.vulgatus.Finally,the fecal microbiota transplantation experiment found that the fecal microbiota of the PNS group could reduce the levels of inflammatory factors IL-1β,IL-6,TNF-α and IL-17 a in the colon of mice,and repair the damaged intestinal barrier.A.muciniphila,significantly increased in PNS group,can effectively reduce LPS-induced RAW264.7cell inflammation.In addition,GC-K has a significant therapeutic effect on colitis,and is one of the medicinal substances in vivo produced by the metabolism of PNS by gut microbiota.Conclusion:Gut microbiota plays an important role in mediating the anti-IBD of PNS.1.PNS can alleviate the symptoms of colitis by regulating the profile of gut microbiota,such as increasing the number of Akkermansia and reducing the abundance of Bacteroides.2.GC-K produced by PNS through gut microbiota metabolism has anti-colitis effect and is one of the pharmacodynamic substances in the body.This article contains 35 figures,7 tables,85 references.