Study On The Mechanism Of Therapeutic Effect Of Total Glucosides Of Paeony On Mice With Ulcerative Colitis

Background and Purpose: Total glucosides of peony(TGP),the extract from Paeonia lactiflora Pall,is well known for immunomodulatory efficacy in clinical practice.However,the mechanism and active ingredients remain largely unclear.Our previous study revealed a very low systemic exposure of TGP components with a predominant gut distribution.The aim of this study was to investigate the involvement of enteric actions as the immunoregulatory mechanism of TGP components.Experimental Approach: Mice received 7 days DSS(3% in drinking water)to establish a model of colitis with or without treatment of TGP or its single component paeoniflorin(PF)or albiflorin(AF).Body weight,colon length,inflammatory and histological changes were assessed.The structure of the gut microbiota was profiled by 16 s rRNA sequencing.Metabolomics study of host and microbial metabolites were employed to find the key metabolic mediators underlying colitis progression and TGP treatment.Key Results: In a mice model of colitis,TGP improved colonic injury and inflammation,and paeoniflorin(PF),a major component in TGP,were responsible for these protective effects.Gut microbiota dysbiosis in colitis mice were alleviated by TGP.Notably,targeted metabolomic analysis revealed that both TGP and PF decreased the accumulation of indole-3-lactic acid(ILA),a microbial metabolite,in the inflamed colon.ILA was further identified as an inhibitor of the drug effect of TGP in colitis mice.Conclusion and Implications: Our findings suggest that TGP can improve ulcerative colitis in mice by down-regulating the intestinal metabolite metabolite indole-3-lactic acid.