Mechanism of astragalin in allevating ulcerative colitis in mice through modulation of the intestinal flora

HUANG Jing; LIAO Yanhua; MO Xinying; YANG Yuting; JIANG Weizhe

doi:10.6039/j.issn.1001-0408.2025.14.04

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Mechanism of astragalin in allevating ulcerative colitis in mice through modulation of the intestinal flora

更新时间：2025-09-24

- Mechanism of astragalin in allevating ulcerative colitis in mice through modulation of the intestinal flora
- ZHONGGUO YAOFANG Vol. 36, Issue 14, Pages: 1709-1716(2025)
- 作者机构：
  
  1.右江民族医学院附属医院药学部，广西百色　533000
  2.广西医科大学药学院，南宁　530021
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2025.14.04
  CLC： R285.5;R965
- Received：07 January 2025，
  
  Revised：2025-05-17，
  
  Accepted：27 May 2025，
  
  Published：30 July 2025
- 稿件说明：
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黄静,廖艳花,莫昕莹,等.紫云英苷调节肠道菌群缓解小鼠溃疡性结肠炎的作用机制[J].中国药房,2025,36(14):1709-1716.

HUANG Jing,LIAO Yanhua,MO Xinying,et al.Mechanism of astragalin in allevating ulcerative colitis in mice through modulation of the intestinal flora[J].ZHONGGUO YAOFANG,2025,36(14):1709-1716.
黄静,廖艳花,莫昕莹,等.紫云英苷调节肠道菌群缓解小鼠溃疡性结肠炎的作用机制[J].中国药房,2025,36(14):1709-1716. DOI： 10.6039/j.issn.1001-0408.2025.14.04.

HUANG Jing,LIAO Yanhua,MO Xinying,et al.Mechanism of astragalin in allevating ulcerative colitis in mice through modulation of the intestinal flora[J].ZHONGGUO YAOFANG,2025,36(14):1709-1716. DOI： 10.6039/j.issn.1001-0408.2025.14.04.

摘要

目的

探究紫云英苷（AG）调节肠道菌群缓解小鼠溃疡性结肠炎（UC）的潜在作用机制。

方法

将雄性C57BL/6小鼠随机分为正常组（CON组）、模型组[葡聚糖硫酸钠（DSS）组]、5-氨基水杨酸组（5-ASA组）、AG低剂量组和高剂量组（AGL、AGH组），每组8只。除CON组外，其余组小鼠以连续饮用3%DSS溶液7 d的方式建立小鼠UC模型；随后，将3%DSS溶液换为水，各药物组小鼠灌胃相应药液，CON组和DSS组小鼠灌胃等体积生理盐水，每天1次，连续7 d。末次灌胃后，比较各组小鼠的体重变化指数、疾病活动指数（DAI）评分、结肠长度和脾脏指数、炎症因子（肿瘤坏死因子α、白细胞介素1β、白细胞介素6）水平；观察各组小鼠结肠组织的病理改变，并比较其病理学评分、杯状细胞占比；检测各组小鼠肠道屏障相关因子[闭合蛋白（occludin）和紧密连接蛋白ZO-1]和炎症相关因子[沉默信息调节因子1（SIRT1）、c-Jun氨基末端激酶（JNK）和p38丝裂原活化的蛋白激酶（p38 MAPK）]mRNA的表达情况；分析各组小鼠的肠道菌群变化情况并检测其肠道代谢物短链脂肪酸水平（SCFAs）含量；以DSS、AG处理的粪菌液为干预手段，通过粪便菌群移植实验进一步验证AG的抗UC机制。

结果

与CON组比较，DSS组小鼠肠道黏膜结构受损严重，炎症细胞跨壁浸润明显；其体重变化指数，结肠长度，杯状细胞占比，occludin、ZO-1、SIRT1 mRNA的表达，Chao1和Shannon指数，乙酸和丁酸含量均显著降低、缩短或下调（

＜0.05）；DAI评分、脾脏指数、炎症因子水平、病理学评分和p38 MAPK、JNK mRNA的表达均显著升高或上调（

＜0.05）。与DSS组比较，AG各剂量组小鼠结肠组织病变有不同程度好转，上述各定量指标均普遍回调（

＜0.05），且AG处理的粪菌液的干预作用与AG基本一致。

结论

AG可改善UC小鼠的相关症状，减轻其炎症反应和结肠组织病理改变；上述作用可能与调节小鼠肠道菌群多样性，增加丁酸、丙酸含量，促进结肠黏膜屏障的修复，进而调控SIRT1/p38 MAPK炎症通路相关基因表达有关。

Abstract

OBJECTIVE

To explore the potential mechanisms of astragalin （AG） in allevating ulcerative colitis （UC） in mice through modulation of the intestinal flora.

METHODS

Male C57BL/6 mice were randomly divided into normal group （CON group）， model group [dextran sodium sulfate （DSS） group]， 5-aminosalicylic acid group （5-ASA group）， AG low-dose group and high-dose group （AGL and AGH groups）， with 8 mice in each group. The mice UC model was established by drinking 3% DSS solution continuously for 7 days in all groups except the CON group. After that， 3% DSS solution was replaced by water， and the mice of each drug group were gavaged with the corresponding drug solution. Mice in the CON and DSS groups were gavaged with an equal volume of normal saline， once a day， for 7 days. After the last gavage， the body weight change index， disease activity index （DAI） score， colon length and spleen index， and levels of inflammatory factors （tumor necrosis factor-α， interleukin-1β， interleukin-6） were compared among the mice in each group； pathological changes in colonic tissues of the mice were observed in each group， and the pathological score and the percentage of goblet cells were compared； mRNA expressions of barrier-related factors [occludin and ZO-1] and inflammation-related factors [silencing information regulatory factor 1 （SIRT1）， c-Jun N-terminal kinase （JNK） and p38 mitogen-activated protein kinase （p38 MAPK）] were detected in each group of mice； the changes in the intestinal flora of mice in each group were analyzed and the contents of intestinal metabolites short-chain fatty acids （SCFAs） was determined. Using DSS and AG-treated fecal bacterial liquid as an intervention， the mechanism of anti-UC effect of AG was further verified by a fecal microbiota transplant experiment.

RESULTS

Compared with the CON group， the intestinal mucosal structure of mice in the DSS group was severely damaged， with obvious infiltration of inflammatory cells collapsing the wall； their body weight change index， colon length， the percentage of goblet cells， mRNA expressions of occludin， ZO-1 and SIRT1， Chao1 and Shannon indexes， and contents of acetic acid and butyric acid were significantly reduced， shortened or down-regulated （

＜0.05）； however， DAI score， spleen index， levels of inflammatory factors， pathological score， as well as mRNA expressions of p38 MAPK and JNK， were all significantly increased or up-regulated （

＜0.05）. Compared with the DSS group， colon tissue lesions of AG mice in all dose groups showed different degrees of improvement， and the above quantitative indexes were generally regressed （

＜0.05）， and the intervention effect of AG-treated fecal bacterial fluid was basically the same as that of AG.

CONCLUSIONS

AG can improve relevant symptoms in UC mice and reduce their inflammatory response and colonic histopathological changes. The above effects may be related to regulating the diversity of intestinal flora in mice， increasing the contents of butyric acid and propionic acid， and promoting the repair of the colonic mucosal barrier， thus regulating the expressions of genes related to the SIRT1/p38 MAPK inflammatory pathway.

关键词

Keywords

references

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