Baitouweng decoction alleviates dextran sulfate sodium-induced ulcerative colitis by regulating intestinal microbiota and the IL-6/STAT3 signaling pathway
Baitouweng decoction alleviates dextran sulfate sodium-induced ulcerative colitis by regulating intestinal microbiota and the IL-6/STAT3 signaling pathway
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白头翁汤通过调节肠道菌群和IL-6/STAT3信号通路减轻右旋糖酐硫酸钠诱导的溃疡性结肠炎
DOI：
10.1016/j.jep.2020.113357
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发表时间：
2021-01-30
影响因子：
5.4
通讯作者：
Liu, Shi-jia
中科院分区：
文献类型：
--
作者：
Chen, Xuan-qing;Lv, Xiang-yu;Liu, Shi-jia
民族药理学相关性：白头翁汤是治疗溃疡性结肠炎（UC）的传统方剂，已有数百年的历史。本研究以葡聚糖硫酸钠（dextran sulfate sodium，DSS）诱导的UC小鼠为模型，观察了BTW的抗炎作用和肠道植物群的变化，并初步探讨了BTW治疗UC的作用机制。研究目的：本研究旨在通过分子生物学和高通量测序技术，阐明BTW治疗UC的作用机制。建立DSS诱导的UC小鼠模型，随机分为对照组、DSS组、BTW组和柳氮磺胺吡啶（SASP）组。除对照组外，各组均灌服3%DSS饮用水7 d，其余两组均灌服BTW和SASP。灌胃10天后处死小鼠。观察各组大鼠体重减轻、疾病活动指数（DAI）、结肠长度、结肠组织病理学改变及炎性细胞因子的表达。结果：BTW能有效减轻UC小鼠的症状和组织病理学评分，降低IL-6、IL-1 β和TNF-α的产生。BTW处理也抑制了IL-6/STAT 3通路的活化。16 S rDNA测序结果显示，与对照组相比，DSS组小鼠肠道植物群紊乱。BTW治疗后肠道植物群多样性明显改善。在门水平上，厚壁菌门与拟杆菌门的比例下降，变形菌门的比例下降。结论：BTW能显著改善急性结肠炎小鼠的炎症症状，其潜在机制可能与多种信号通路有关，包括肠道菌群的调节和炎症信号通路的调节，如IL-6/STAT 3。
Ethnopharmacological relevance: Baitouweng (BTW) decoction, a Chinese traditional medicine prescription, has been used to treat ulcerative colitis (UC) over hundreds of years. In this study, we investigated the anti-inflammatory effects of BTW and intestinal flora of dextran sulfate sodium (DSS)-induced UC mice, and we investigated the mechanism of BTW in the preliminary treatment of UC.Aim of study: The aim of this study was to elucidate the mechanism of BTW in treating UC through molecular biology and high-throughput sequencing.Methods: DSS-induced UC mice were established and randomly divided into the following four groups: control group, DSS group, BTW group and sulfasalazine (SASP) group. Except for the control group, 3% DSS drinking water was given to each group for 7 days, and the other two groups were intragastrically administered with BTW and SASP. Mice were sacrificed after gavage for 10 days. Body weight loss, disease activity index (DAI), colon length, colon histopathology and the expression of inflammatory cytokines were measured. Intestinal content samples were collected, and intestinal flora differences were analyzed by 16 S rDNA sequencing.Results: BTW effectively reduced the symptoms and histopathological score of UC mice, and it reduced the production of IL-6, IL-1 beta and TNF-alpha. Activation of the IL-6/STAT3 pathway was also suppressed by BTW treatment. Moreover, 16 S rDNA sequencing showed that the intestinal flora of mice in the DSS group was disordered compared to the control group. After treatment with BTW, the diversity of intestinal flora was significantly improved. At the phylum level, the proportion of Firmicutes to Bacteroidetes was decreased, and the ratio of Proteobacteria was decreased. At the genus level, the relative abundance of Escherichia-Shigella was decreased, but that of Lactobacillus and Akkermansia were increased.Conclusion: BTW significantly improved the inflammatory symptoms of mice with acute colitis, and the latent mechanism of BTW may be related to various signaling pathways, including the modulation of intestinal microflora and inflammatory signaling pathways, such as IL-6/STAT3.