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中国白头翁水灌肠通过抑制炎症和调节结肠黏膜微生物群缓解葡聚糖硫酸钠诱导的结肠炎。

Anemone chinensis Bunge aqueous enema alleviates dextran sulfate sodium-induced colitis via inhibition of inflammation and regulation of the colonic mucosal microbiota.

机构信息

Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277 Yanta West Road, Xi'an, Shaanxi, 710061, PR China; Central Laboratory, Shanxi Provincial People's Hospital, Affiliated of Shanxi Medical University, Taiyuan, Shanxi, 030012, PR China.

Department of Nephrology, Shanxi Provincial People's Hospital, Affiliate of Shanxi Medical University, Taiyuan, Shanxi, 030012, PR China.

出版信息

J Ethnopharmacol. 2022 Apr 24;288:114916. doi: 10.1016/j.jep.2021.114916. Epub 2022 Jan 5.

DOI:10.1016/j.jep.2021.114916
PMID:34998930
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Although the incidence of ulcerative colitis (UC) increases every year, there is still a lack of satisfactory treatment options. Anemone chinensis Bunge (AB), a traditional Chinese herb, is a potent compound that can be prepared as a decoction, and then administered as an enema to relieve UC symptoms. However, the therapeutic effect and mechanisms of aqueous AB on UC are still unknown.

AIM OF THE STUDY

This study investigates the potential therapeutic value and mechanism of AB aqueous enema for UC.

MATERIALS AND METHODS

First, the practical components in aqueous AB were extracted and identified by UPLC-MS/MS. Second, the potential active targets and target genes related to UC were predicted, mapped, and analyzed by network pharmacology. Then, the effects of AB aqueous enema on UC were assessed using the dextran sulfate sodium (DSS)-induced colitis model with mice. Finally, the level of inflammation, the expression level of proteins associated with the colonic mucosal barrier, and the microbiota associated with the intestinal mucosal were investigated.

RESULTS

Fourteen active ingredients in AB were identified. The network pharmacology-based analysis demonstrated that the active ingredients possibly affected ten key targets, such as IL-6, TNF, and PTGS2. They are also related to the tight junction proteins ZO-1, occludin, and claudin-1. Furthermore, mice treated with DSS developed severe mucosal colitis. AB aqueous enema decreased the disease activity index (DAI), significantly inhibited colonic damage, and greatly decreased colon length shortening (p < 0.05). AB also significantly restored tight junction proteins and the associated mucin proteins mucin-2 (MUC2) and mucin-3A (MUC3A). In addition, the diversity of the gut microbiota after administration of DSS was significantly decreased. However, the diversity was entirely restored after AB treatment. Recovery of the abundance of colonic mucosal bacteria, especially Lactobacillus reuteri and Lactobacillus gasseri, occurred at the species level after AB treatment. In vitro, AB can be utilized by the two bacteria, especially under glucose deficiency.

CONCLUSIONS

Our study demonstrated that the AB aqueous enema alleviated colitis by restoring intestinal barrier proteins and regulating the gut microbiota.

摘要

民族药理学相关性

尽管溃疡性结肠炎(UC)的发病率逐年上升,但仍缺乏令人满意的治疗选择。白头翁(AB)是一种传统的中药,是一种有效的化合物,可以制成煎剂,然后通过灌肠来缓解 UC 症状。然而,AB 水浸剂治疗 UC 的疗效和机制尚不清楚。

研究目的

本研究旨在探讨 AB 水浸剂治疗 UC 的潜在治疗价值和机制。

材料和方法

首先,通过 UPLC-MS/MS 提取并鉴定 AB 水浸剂中的实际成分。其次,通过网络药理学预测、映射和分析与 UC 相关的潜在活性靶点和靶基因。然后,用葡聚糖硫酸钠(DSS)诱导的结肠炎模型评估 AB 水浸剂对 UC 的作用。最后,研究 AB 水浸剂对肠道黏膜炎症水平、与结肠黏膜屏障相关的蛋白质表达水平以及与肠道黏膜相关的微生物群的影响。

结果

鉴定出 AB 中的 14 种活性成分。基于网络药理学的分析表明,这些活性成分可能影响到 10 个关键靶点,如 IL-6、TNF 和 PTGS2。它们还与紧密连接蛋白 ZO-1、occludin 和 claudin-1 有关。此外,用 DSS 处理的小鼠发生严重的黏膜结肠炎。AB 水浸剂降低疾病活动指数(DAI),显著抑制结肠损伤,显著减少结肠长度缩短(p<0.05)。AB 还显著恢复了紧密连接蛋白和相关粘蛋白蛋白 MUC2 和 MUC3A。此外,DSS 给药后肠道微生物群的多样性显著降低。然而,AB 治疗后完全恢复了多样性。AB 治疗后,结肠黏膜细菌的丰度得到了完全恢复,特别是 Lactobacillus reuteri 和 Lactobacillus gasseri。体外实验表明,AB 可以被这两种细菌利用,尤其是在葡萄糖缺乏的情况下。

结论

本研究表明,AB 水浸剂通过恢复肠道屏障蛋白和调节肠道微生物群来缓解结肠炎。

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