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枳椇子汤通过调节肠道微生物群及其相关代谢产物,并抑制TLR4/NF-κB/NLRP3通路来改善溃疡性结肠炎。

Zhili decoction ameliorates ulcerative colitis by modulating gut microbiota and related metabolite, and inhibiting the TLR4/NF-κB/NLRP3 pathway.

作者信息

Tan Tianying, Chen Qin, Chen Ping, Li Shuangshuang, Hu Wenting, Yang Tao, Jia Yingtian

机构信息

College of Clinical Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, China.

Department of Anorectal, Kunming Municipal Hospital of Traditional Chinese Medicine, The Third Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming, China.

出版信息

Front Pharmacol. 2024 Dec 23;15:1481273. doi: 10.3389/fphar.2024.1481273. eCollection 2024.

DOI:10.3389/fphar.2024.1481273
PMID:39764470
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11701441/
Abstract

ETHNOPHARMACOLOGICAL IMPORTANCE

Zhili decoction (ZLD) is a traditional Chinese medicine prescription for ulcerative colitis (UC). However, the mechanism by which ZLD exerts its therapeutic effects in the context of UC remains unclear.

AIM OF STUDY

The aim of this study was to investigate the effects of ZLD on the gut microbiota and related fecal metabolite levels using a mouse model of UC. In addition, we examined the underlying molecular mechanisms responsible for these effects.

MATERIALS AND METHODS

The major components of ZLD were detected by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). An integrated approach employing 16S rRNA and fecal metabolomics was employed to assess the potential impacts of ZLD on gut flora abundance and diversity, fecal metabolite levels, and various metabolic pathways. To further investigate the potential mechanisms of ZLD in treating UC, the expression of genes and proteins were examined by RT-qPCR, immunohistochemical staining and Western blotting.

RESULTS

ZLD markedly alleviated symptoms and inflammatory injury in mice with UC. DSS induced notable alterations in the gut microbiome, and ZLD enhanced gut microbial diversity in UC mice by augmenting the abundance of Bacteroidota, Christensenella, , etc., while reducing the / ratio. ZLD treatment significantly modified the metabolic profile of mice with UC. It significantly suppressed the arachidonic acid metabolic pathway and promoted the butyrate acid metabolic pathway. ZLD reduced inflammatory factors and inhibited TLR4/NF-κB/NLRP3 pathway expression. In addition, correlation analysis demonstrated a close relationship between gut microbes, fecal metabolites, and inflammatory factors.

CONCLUSION

ZLD alleviated UC by regulating gut flora, modulating related metabolite levels, and inhibiting TLR4/NF-κB/NLRP3 pathway.

摘要

民族药理学重要性

枳椇子汤(ZLD)是一种用于治疗溃疡性结肠炎(UC)的中药方剂。然而,ZLD在UC背景下发挥治疗作用的机制尚不清楚。

研究目的

本研究旨在使用UC小鼠模型研究ZLD对肠道微生物群及相关粪便代谢物水平的影响。此外,我们还研究了造成这些影响的潜在分子机制。

材料与方法

采用超高效液相色谱-质谱联用仪(UPLC-MS)检测ZLD的主要成分。采用16S rRNA和粪便代谢组学的综合方法评估ZLD对肠道菌群丰度和多样性、粪便代谢物水平以及各种代谢途径的潜在影响。为了进一步研究ZLD治疗UC的潜在机制,通过RT-qPCR、免疫组织化学染色和蛋白质印迹法检测基因和蛋白质的表达。

结果

ZLD显著减轻了UC小鼠的症状和炎症损伤。葡聚糖硫酸钠(DSS)诱导肠道微生物群发生显著变化,ZLD通过增加拟杆菌门、克里斯滕森菌属等的丰度,同时降低/比值,增强了UC小鼠的肠道微生物多样性。ZLD治疗显著改变了UC小鼠的代谢谱。它显著抑制花生四烯酸代谢途径,促进丁酸代谢途径。ZLD降低了炎症因子水平,抑制了TLR4/NF-κB/NLRP3信号通路的表达。此外,相关性分析表明肠道微生物、粪便代谢物和炎症因子之间存在密切关系。

结论

ZLD通过调节肠道菌群、调节相关代谢物水平和抑制TLR4/NF-κB/NLRP3信号通路来缓解UC。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9026/11701441/ecd14aa0d3df/fphar-15-1481273-g011.jpg
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