Background: Atractylodes lancea (Thunb.) DC. is used in China as a folk medicine for gastrointestinal disorder treatment, and its effect on treating gastrointestinal disorders is enhanced when it is fried in bran. Atractylodes lancea rhizome polysaccharide (ALP) are a group of active substances in Atractylodes lancea rhizome,ALP has good anti-inflammatory, oxidative, immunological, and intestinal flora-regulating activities, suggesting that it is a potential drug option for treating ulcerative colitis (UC). However, the effects and mechanisms of raw Atractylodes lancea rhizome polysaccharide (SALP) as well as bran-fried Atractylodes lancea rhizome polysaccharide (FALP) on dextran sodium sulfate (DSS)-induced UC in mice are unclear.

Objective: This study aimed to investigate the comparative therapeutic effects of SALP and FALP in mice with UC and assess their potential mechanisms of action.

Methods: BALB/c mice were regularly administered 3.5% DSS to develop and establish an acute UC model, following which SALP-L, SALP-H, FALP-L, FALP-H and sulfasalazine (SASP) were administered for 10 days continuously. The body weight, disease activity index (DAI), organ index, colon length, histopathological damage, proinflammatory cytokine expression level, tight junction protein expression, transcriptome, metabolomics, and 16S rDNA of the mouse model were examined to compare the efficacy and mechanisms of action of SALP and FALP in UC treatment.

Results: Both SALP and FALP significantly alleviated clinical signs (increased body weight, decreased DAI scores, reduced colonic pathological damage, and others), improved intestinal barrier (promoted Occludin and ZO-1 expression), and reduced intestinal inflammation (inhibited IL-1β and TNF-α [proinflammatory cytokines] expression) in DSS-induced acute UC mice. Metabolomics revealed that both SALP and FALP reversed arachidonic acid, lactic acid, ethanolamine, 9,12-octadecadienoic acid, phosphoric acid, and 1-monopalmitin levels in colonic tissues. In addition, they attenuated intestinal flora disorders in DSS-treated mice by increasing the relative abundance of the beneficial bacteria Lachnospiraceae_NK4A136_group and Alistipes while decreasing that of the harmful bacteria Alloprevotella and Prevotellaceae_UCG_001. Of note, the improvement effect of FALP was better than that of SALP in these results.

Conclusions: Both SALP and FALP reduced colitis symptoms by repairing the intestinal barrier, modulating intestinal flora, and improving the metabolism of compounds in colonic tissues. Of note, The therapeutic effects of FALP were all stronger than those of SALP.