Improvement mechanism study of kushenol F on ulcerative colitis mice by regulating gut microbiota and immune response

HE Xudong; SONG Chengzhu; NI Haoyu; HU Yunkai; LI Min; CHEN Dajun; SU Wentao; YU Jie; YANG Xingxin

doi:10.6039/j.issn.1001-0408.2024.17.06

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Improvement mechanism study of kushenol F on ulcerative colitis mice by regulating gut microbiota and immune response

更新时间：2025-09-23

- Improvement mechanism study of kushenol F on ulcerative colitis mice by regulating gut microbiota and immune response
- ZHONGGUO YAOFANG Vol. 35, Issue 17, Pages: 2088-2095(2024)
- 作者机构：
  
  云南中医药大学中药学院，昆明　650500
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2024.17.06
  CLC： R966
- Received：15 March 2024，
  
  Revised：2024-08-06，
  
  Accepted：07 August 2024，
  
  Published：15 September 2024
- 稿件说明：
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何旭东,宋成竹,倪皓雨,等.苦参醇F调节肠道菌群及免疫应答对溃疡性结肠炎小鼠的改善作用机制研究 [J].中国药房,2024,35(17):2088-2095.

HE Xudong,SONG Chengzhu,NI Haoyu,et al.Improvement mechanism study of kushenol F on ulcerative colitis mice by regulating gut microbiota and immune response[J].ZHONGGUO YAOFANG,2024,35(17):2088-2095.
何旭东,宋成竹,倪皓雨,等.苦参醇F调节肠道菌群及免疫应答对溃疡性结肠炎小鼠的改善作用机制研究 [J].中国药房,2024,35(17):2088-2095. DOI： 10.6039/j.issn.1001-0408.2024.17.06.

HE Xudong,SONG Chengzhu,NI Haoyu,et al.Improvement mechanism study of kushenol F on ulcerative colitis mice by regulating gut microbiota and immune response[J].ZHONGGUO YAOFANG,2024,35(17):2088-2095. DOI： 10.6039/j.issn.1001-0408.2024.17.06.

摘要

目的

探究苦参醇F（KSCF）治疗溃疡性结肠炎（UC）小鼠的作用机制。

方法

采用网络药理学与分子对接预测KSCF干预UC的潜在靶点。将C57BL/6J小鼠按体重分为模型组、阳性对照组（柳氮磺胺吡啶，703 mg/kg）、KSCF组（100 mg/kg ）和正常组，每组6只；采用饮用葡聚糖硫酸钠溶液的方法建立小鼠UC模型；造模期间灌胃给药，每天1次，连续7 d。末次给药后，对小鼠疾病活动指数（DAI）进行评分；测量小鼠结肠长度；观察小鼠结肠组织病理形态学变化；检测小鼠血清中脂多糖（LPS）及结肠中髓过氧化物酶（MPO）、一氧化氮（NO）和超氧化物歧化酶（SOD）水平；检测小鼠结肠组织中闭合蛋白（occludin）、紧密连接蛋白1（ZO-1）表达水平；检测小鼠脾脏中CD3

T、CD4

T、CD8

T淋巴细胞比例及CD4

/CD8

值变化；采用16S rDNA测序法分析结肠微生物变化。

结果

网络药理学结果显示，KSCF可能调节磷脂酰肌醇3激酶/蛋白激酶B、核因子κB（NF-κB）等信号通路治疗UC。分子对接结果表明，KSCF与NF-κB p65蛋白结合最稳定。动物实验结果表明，与模型组比较，KSCF组小鼠结肠组织病理形态学特征得到改善；DAI评分、血清LPS水平、结肠组织中MPO及NF-κB p65磷酸化和NLRP3蛋白表达水平、脾脏中CD8

T淋巴细胞比例显著降低（

＜0.05）；小鼠体重，结肠组织中SOD水平、occludin和ZO-1表达水平，脾脏中CD3

T、CD4

T淋巴细胞比例及CD4

/CD8

值显著升高（

＜0.05）；肠道中厚壁菌门、放线菌门、阿克曼氏菌属和乳酸杆菌属丰度增加，变形菌门丰度减少，菌群结构向正常组趋近。

结论

KSCF通过修复肠道微生态失调、增强免疫应答来抑制结肠炎症反应，改善肠屏障完整性来缓解UC。

Abstract

OBJECTIVE

To explore the action mechanism of kushenol F （KSCF） in treating ulcerative colitis （UC） in mice.

METHODS

The potential targets of KSCF intervening in UC were predicted with network pharmacology and molecular docking. C57BL/6J mice were randomly divided by body weight into model group， positive control group （sulfasalazine， 703 mg/kg）， KSCF group （100 mg/kg）， and normal group， with 6 mice per group. The UC model of mice was induced by dextran sulfate sodium solution. During the modeling period， the mice were given relevant medicine intragastrically， once a day， for 7 consecutive days. After the last administration， the disease activity index （DAI） of the mice was scored； the length of the mice’s colon was measured； pathological changes in the colon tissue of mice were observed； the levels of lipopol

ysaccharide （LPS） in serum， myeloperoxidase （MPO）， nitric oxide （NO） and superoxide dismutase （SOD） in the colon were detected in mice； the expression levels of occludin and ZO-1 in colon tissue of mice were detected； the proportions of CD3

T， CD4

T， and CD8

T lymphocytes in the spleen and the ratio of CD4

/CD8

were detected； changes in colonic microbiota were analyzed by 16S rDNA sequencing.

RESULTS

Results of network pharmacology indicated that KSCF may treat UC by regulating signaling pathways such as phosphatidylinositol-3 kinase/protein kinase B （PI3K/AKT） and nuclear factor kappa B （NF-κB）. Molecular docking results showed that KSCF bound most stably with NF-κB p65 protein. Animal experiment results demonstrated that， compared with the model group， the pathological characteristics of colon tissue in mice were improved in KSCF group. DAI scores， serum levels of LPS， the levels of MPO， NF-κB p65 phosphorylation and NLRP3 protein expression in the colon， and the proportion of CD8

T lymphocytes in the spleen were reduced significantly （

＜0.05）. Body weight， SOD levels， expression levels of occludin and ZO-1 in the colon， proportions of CD3

T and CD4

T lymphocytes， and the CD4

/CD8

ratio in the spleen were significantly increased （

＜0.05）； the abundance of Firmicutes， Actinobacteria

， Akkermansia

， and

Lactobacillus

genera were increased， while Proteobacteria decreased； the microbial community structure tended towards that of the normal group.

CONCLUSIONS

KSCF alleviates UC by restoring intestinal microbial imbalance， enhancing immune response， and inhibiting colonic inflammatory responses， thereby improving intestinal barrier integrity.

关键词

Keywords

references

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