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Alisol B 23-Acetate Ameliorates Azoxymethane/Dextran Sodium Sulfate-Induced Male Murine Colitis-Associated Colorectal Cancer via Modulating the Composition of Gut Microbiota and Improving Intestinal Barrier.

ABSTRACT: Hunting for natural compounds that can modulate the structure of the intestinal flora is a new hotspot for colitis-associated cancer (CAC) prevention or treatment. Alisol B 23-acetate (AB23A) is a natural tetracyclic triterpenoid found in Alismatis rhizoma which is well known for dietary herb. Alismatis rhizoma is often used clinically to treat gastrointestinal diseases in China. In this study, we investigated the potential prevention of AB23A in male mouse models of azoxymethane (AOM) and dextran sulfate sodium (DSS)-induced CAC. AB23A intervention alleviated the body weight loss, disease activity index, colon tumor load, tissue injury, and inflammatory cytokine changes in CAC mice. AB23A intervention leads to remarkable reductions in the activation of TLR, NF-κB and MAPK. AB23A significantly decreased the phosphorylation of p38, ERK, and JNK and up-regulated mucin-2 and the expression of tight junction proteins. The gut microbiota of AB23A-interfered mice was characterized with high microbial diversity, the reduced expansion of pathogenic bacteria, such as Klebsiella, Citrobacter, and Akkermansia, and the increased growth of bacteria including Bacteroides, Lactobacillus, and Alloprevotella. These data reveal that AB23A has the potential to be used to treat CAC in the future.

SUBMITTER: Zhu HC

PROVIDER: S-EPMC8117151 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Alisol B 23-Acetate Ameliorates Azoxymethane/Dextran Sodium Sulfate-Induced Male Murine Colitis-Associated Colorectal Cancer via Modulating the Composition of Gut Microbiota and Improving Intestinal Barrier.

Zhu Huai-Chang HC Jia Xiao-Kang XK Fan Yong Y Xu Shao-Hua SH Li Xiao-Yan XY Huang Ming-Qing MQ Lan Meng-Liu ML Xu Wen W Wu Shui-Sheng SS

Frontiers in cellular and infection microbiology 20210429

Hunting for natural compounds that can modulate the structure of the intestinal flora is a new hotspot for colitis-associated cancer (CAC) prevention or treatment. Alisol B 23-acetate (AB23A) is a natural tetracyclic triterpenoid found in Alismatis rhizoma which is well known for dietary herb. Alismatis rhizoma is often used clinically to treat gastrointestinal diseases in China. In this study, we investigated the potential prevention of AB23A in male mouse models of azoxymethane ( ...[more]

PMID: 33996624

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Project description:BackgroundInflammatory bowel disease (IBD) encompasses chronic inflammation of the colon and rectum, posing significant health challenges. Previous studies have shown potential therapeutic effects of natural compounds on IBD. Chrysin, a naturally occurring flavonoid, has been suggested to modulate inflammatory pathways and gut microbiota, but its comprehensive impact on ulcerative colitis remains inadequately explored.MethodsThis study employed a dextran sulfate sodium (DSS)-induced ulcerative colitis model in mice to investigate the effects of Chrysin. Using network pharmacology, we identified key signaling pathways potentially influenced by Chrysin. Experimental approaches included measuring disease activity index scores, serum levels of TNF-α, and assessing colon damage histologically. Transcriptomic and microbiome analyses were conducted to examine changes in gene expression and gut bacterial populations, respectively. Additionally, metabolomic profiling was used to identify alterations in colon metabolites.ResultsChrysin treatment significantly mitigated weight loss and reduced disease activity index scores in DSS-induced mice. There was a notable decrease in serum TNF-α levels and less histological damage in the colon. Transcriptomic analysis revealed significant alterations in gene expression within the NF-κB and IL-17 signaling pathways. Microbiome analysis showed significant shifts in the populations of Bacteroidetes and Firmicutes. Metabolomics analysis identified changes in 298 colon metabolites, implicating several essential metabolic pathways.ConclusionsThe findings suggest that Chrysin exerts a dual-action therapeutic effect on ulcerative colitis by reducing inflammation and modulating the gut microbiota. These multifaceted impacts highlight Chrysin's potential utility as a novel therapeutic agent in the clinical management of IBD, offering valuable insights into its mechanisms of action and paving the way for future clinical trials.

Dataset Information

Alisol B 23-Acetate Ameliorates Azoxymethane/Dextran Sodium Sulfate-Induced Male Murine Colitis-Associated Colorectal Cancer via Modulating the Composition of Gut Microbiota and Improving Intestinal Barrier.

Publications

Alisol B 23-Acetate Ameliorates Azoxymethane/Dextran Sodium Sulfate-Induced Male Murine Colitis-Associated Colorectal Cancer <i>via</i> Modulating the Composition of Gut Microbiota and Improving Intestinal Barrier.

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