Mechanism prediction and verification of <italic style="font-style: italic">Cistanche deserticola</italic> in the treatment of inflammatory bowel disease

QIAO Ming; ZHU Yi; HU Junping; YANG Jianhua

doi:10.6039/j.issn.1001-0408.2024.21.02

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Mechanism prediction and verification of Cistanche deserticola in the treatment of inflammatory bowel disease

更新时间：2025-09-25

- Mechanism prediction and verification of Cistanche deserticola in the treatment of inflammatory bowel disease
- ZHONGGUO YAOFANG Vol. 35, Issue 21, Pages: 2582-2589(2024)
- 作者机构：
  
  1.新疆医科大学第一附属医院药学部，乌鲁木齐　830011
  2.新疆药物临床研究重点实验室，乌鲁木齐　830011
  3.新疆医科大学药学院，乌鲁木齐　830017
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2024.21.02
  CLC： R965
- Received：11 May 2024，
  
  Revised：2024-09-14，
  
  Accepted：18 September 2024，
  
  Published：15 November 2024
- 稿件说明：
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谯明,朱毅,胡君萍,等.肉苁蓉治疗炎症性肠病的作用机制预测及验证[J].中国药房,2024,35(21):2582-2589.

QIAO Ming,ZHU Yi,HU Junping,et al.Mechanism prediction and verification of Cistanche deserticola in the treatment of inflammatory bowel disease[J].ZHONGGUO YAOFANG,2024,35(21):2582-2589.
谯明,朱毅,胡君萍,等.肉苁蓉治疗炎症性肠病的作用机制预测及验证[J].中国药房,2024,35(21):2582-2589. DOI： 10.6039/j.issn.1001-0408.2024.21.02.

QIAO Ming,ZHU Yi,HU Junping,et al.Mechanism prediction and verification of Cistanche deserticola in the treatment of inflammatory bowel disease[J].ZHONGGUO YAOFANG,2024,35(21):2582-2589. DOI： 10.6039/j.issn.1001-0408.2024.21.02.

摘要

目的

探究肉苁蓉治疗炎症性肠病（IBD）的作用机制。

方法

借助中药系统药理学数据库与分析平台结合文献报道筛选肉苁蓉活性成分；采用Swiss Target Prediction平台获取活性成分靶点；采用GeneCards和OMIM数据库收集疾病靶点；构建蛋白质-蛋白质相互作用网络和“药物-成分-疾病-靶点”网络，筛选核心成分和核心靶点，然后进行基因本体（GO）、京都基因和基因组百科全书（KEGG）通路分析，并对核心靶点和核心成分进行分子对接验证。建立IBD小鼠模型，分为模型组、阳性对照组（地塞米松，0.4 mg/kg）、肉苁蓉提取物组（100、200、400 mg/kg），另设空白对照组，每组8只。各组小鼠给予相应药物，每天1次，连续7 d。计算各组小鼠疾病活动指数（DAI）及结肠长度，观察小鼠结肠组织病理形态，检测小鼠结肠组织中炎症因子[白细胞介素6（IL-6）、IL-10、IL-1β、髓过氧化物酶（MPO）、肿瘤坏死因子α（TNF-α）]水平和核心靶点蛋白表达情况。

结果

共得到肉苁蓉活性成分39个，肉苁蓉活性成分治疗IBD的潜在靶点232个；肉苁蓉治疗IBD的核心成分分别为槲皮素、苏齐内酯、

-谷甾醇、肉苁蓉苷H，核心靶点分别为TNF（肿瘤坏死因子）、AKT1（蛋白激酶B1）、STAT3（信号转导和转录激活因子3）、EGFR（表皮生长因子受体）、SRC（非受体酪氨酸激酶）。GO和KEGG通路分析结果显示，肉苁蓉治疗IBD的生物过程主要与蛋白质磷酸化、凋亡负调控等有关，主要涉及磷脂酰肌醇3激酶（PI3K）/AKT、EGFR酪氨酸激酶抑制剂耐药等信号通路。分子对接结果显示，肉苁蓉核心成分与核心靶点的结合能均小于－4.7 kJ/mol。动物实验结果显示，经肉苁蓉提取物干预后，小鼠体重、结肠长度显著增加（

＜0.05或

＜0.01）；DAI显著降低（

＜0.05或

＜0.01）；结肠黏膜充血、水肿明显减轻，结肠组织病理学评分显著降低（

＜0.05或

＜0.01）；结肠组织中IL-6、IL-1β、MPO、TNF-α水平和PI3K、磷酸化PI3K（p-PI3K）、EGFR、TNF-α、STAT3、磷酸化STAT3（p-STAT3）、AKT1、磷酸化AKT1（p-AKT1）、SRC蛋白表达水平均显著降低（

＜0.05或

＜0.01），IL-10水平均显著升高（

＜0.01）。

结论

肉苁蓉具有治疗IBD的作用，其具体作用机制可能与调节SRC/EGFR/PI3K/AKT信号通路有关。

Abstract

OBJECTIVE

To investigate the mechanism of

Cistanche deserticola

in the treatment of inflammatory bowel disease （IBD）.

METHODS

The active components of

C. deserticola

were screened based on TCMSP and literature reports. The targets of active ingredients were obtained via Swiss Target Prediction platform. Then the disease targets were obtained by searching GeneCards and OMIM databases. PPI network and “drug-compound-disease-target” network were constructed. The core components and core targets were screened. GO and KEGG enrichment analyses were performed， and molecular docking verification was conducted for core targets and core components. The IBD mice model was established and divided into model group， positive control group （dexamethasone， 0.4 mg/kg） and

C. deserticola

extract group （100， 200， 400 mg/kg）； blank control group was set， with 8 mice in each group. Each group was given relevant medicine， once a day， for 7 consecutive days. Disease activity index （DAI） score and colon length were calculated， and the path

ological morphology of the colon of mice was observed. The levels of inflammatory factors [interleukin-6 （IL-6）， IL-1β， IL-10， myeloperoxidase （MPO），tumor necrosis factor-α （TNF-α）

]

in colon tissue， and protein expressions of core targets were detected.

RESULTS

A total of 39 active ingredients and 232 potential targets of

C. deserticola

in the treatment of IBD were obtained. The treatment of IBD with

C. deserticola

might be related to core components such as quercetin， suchilactone，

-sitosterol and cistanoside H， and core targets such as TNF， AKT1， STAT3， EGFR and SRC. GO and KEGG pathway analysis predicted that the biological processes of

C. deserticola

in the treatment of IBD were mainly related to protein phosphorylation， and negative regulation of apoptosis， mainly involving PI3K/AKT and EGFR tyrosine kinase inhibitor resistance signaling pathways. The results of molecular docking showed that the binding energy between the core components and core target of

C. deserticola

was less than －4.7 kJ/mol. Animal experiment results showed that after intervention with

C. deserticola

extract， the body weight and colon length of mice significantly increased （

＜0.05 or

＜0.01）， while DAI decreased significantly （

＜0.05 or

＜0.01）. The congestion and edema of colon mucosa were significantly reduced， and the pathological score of colon tissue was significantly decreased （

＜0.05 or

＜0.01）； the levels of IL-6， IL-1β， MPO and TNF-α， as well as the protein expressions of PI3K， phosphorylated PI3K （p-PI3K）， EGFR， TNF-α， STAT3， phosphorylated STAT3 （p-STAT3）， AKT1， phosphorylated AKT1 （p-AKT1） and SRC in colon tissue were reduced significantly （

＜0.05 or

＜0.01）， while the level of IL-10 was significantly increased in model group （

＜0.01）.

CONCLUSIONS

C. deserticola

may alleviate IBD by regulating the SRC/EGFR/PI3K/AKT signaling pathway.

关键词

Keywords

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Mechanism prediction and verification of Cistanche deserticola in the treatment of inflammatory bowel disease

DOI：10.6039/j.issn.1001-0408.2024.21.02

摘要

Abstract

关键词

Keywords

references