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

您当前的位置：

首页 >

文章列表页 >

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

更新时间：2024-11-08

- 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
- Published：15 November 2024，
  
  Received：11 May 2024，
  
  Revised：14 September 2024，
- 稿件说明：
移动端阅览
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 ^Δ[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 ^Δ[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

肉苁蓉炎症性肠病网络药理学分子对接实验验证

Keywords

inflammatory bowel diseasenetwork pharmacologymolecular dockingexperimental verification

references

包云丽，汪哲，唐海茹，等. 1990－2019年中国炎症性肠病疾病负担及变化趋势分析[J]. 中国全科医学，2023，26（36）：4581-4586.

BAO Y L，WANG Z，TANG H R，et al. Disease burden and variation tendency of inflammatory bowel disease in China from 1990 to 2019[J]. Chin Gen Pract，2023，26（36）：4581-4586.

DOLINGER M T，KAYAL M. Intestinal ultrasound as a non-invasive tool to monitor inflammatory bowel disease activity and guide clinical decision making[J]. World J Gastroenterol，2023，29（15）：2272-2282.

刘艺，刘源，孙志其，等. 中药及有效成分靶向M1/M2巨噬细胞极化平衡治疗炎症性肠病的研究进展[J]. 中国实验方剂学杂志，2024，30（2）：276-286.

LIU Y，LIU Y，SUN Z Q，et al. Treatment of inflammatory bowel disease by targeting M1/M2 macrophage polari- zation balance with traditional Chinese medicine and active components：a review[J]. Chin J Exp Tradit Med Formulae，2024，30（2）：276-286.

方洒，吴开春，时永全，等. 维得利珠单抗一线及后线治疗炎症性肠病的疗效比较[J]. 胃肠病学和肝病学杂志，2024，33（1）：55-58.

FANG S，WU K C，SHI Y Q，et al. Comparison of the efficacy of vedolizumab on inflammatory bowel disease in the first and not line treatments[J]. Chin J Gastroenterol Hepatol，2024，33（1）：55-58.

江学良. 中国中西医结合炎症性肠病质量控制指标共识[J]. 中华消化病与影像杂志，2021，11（4）：149-151.

JIANG X L. Consensus on quality control indicators of integrated Chinese and Western medicine for inflammatory bowel disease in China[J]. Chin J Dig Med Imageology Electron Ed，2021，11（4）：149-151.

国家药典委员会. 中华人民共和国药典：一部[M]. 2020年版. 北京：中国医药科技出版社，2020：140-142.

Chinese Pharmacopoeia Commission. Pharmacopoeia of the People’s Republic of China：Vol Ⅰ[M]. 2020 edition. Beijing：China Medical Science Press，2020：140-142.

ZHOU S Q，FENG D，ZHOU Y X，et al. Analysis of the active ingredients and health applications of Cistanche[J]. Front Nutr，2023，10：1101182.

周亚西，周士琦，冯朵，等. 肉苁蓉生物活性成分及其免疫功效研究进展[J]. 食品科技，2022，47（6）：133-139.

ZHOU Y X，ZHOU S Q，FENG D，et al. Progress in understanding the bioactive components and immune efficacy of Cistanche[J]. Food Sci Technol，2022，47（6）：133-139.

JIA Y M，GUAN Q N，JIANG Y，et al. Amelioration of dextran sulphate sodium-induced colitis in mice by echinacoside-enriched extract of Cistanche tubulosa[J]. Phytother Res，2014，28（1）：110-119.

MAZZON E，ESPOSITO E，DI PAOLA R，et al. Effects of verbascoside biotechnologically produced by Syringa vulgaris plant cell cultures in a rodent model of colitis[J]. Naunyn Schmiedebergs Arch Pharmacol，2009，380（1）：79-94.

闫文杰，冯朵，张绍时，等. 基于网络药理学与动物实验探究肉苁蓉总苷对炎症性肠病的作用机制[J]. 中国食品学报，2023，23（10）：1-11.

YAN W J，FENG D，ZHANG S S，et al. The mechanism of total glycosides of Cistanche deserticola Y.Ma on inflammatory bowel disease based on network pharmaco- logy and animal experiments[J]. J Chin Inst Food Sci Technol，2023，23（10）：1-11.

HUANG P，HUANG T，LI D S，et al. Molecular mechanism of Xixin-ganjiang herb pair treating chronic obstructive pulmonary disease-integrated network pharmacology and molecular docking[J]. Evid Based Complement Alternat Med，2021，2021：5532009.

HUANG S J，MU F，LI F，et al. Potential mechanism study of herbal pair Schizonepetae Herba and Saposhnikoviae Radix against coronavirus pneumonia via network pharmacology and molecular docking[J]. Nat Prod Res Dev，2020，32（6）：1087-1098.

ZHU L，GU P Q，SHEN H. Protective effects of berberine hydrochloride on DSS-induced ulcerative colitis in rats[J]. Int Immunopharmacol，2019，68：242-251.

SONG J Z，CHEN Y Y，LV Z Y，et al. Structural characteri- zation of a polysaccharide from Alhagi honey and its protective effect against inflammatory bowel disease by modulating gut microbiota dysbiosis[J]. Int J Biol Macromol，2024，259（Pt 1）：128937.

XU D，WU Q Y，LIU W Y，et al. Therapeutic efficacy and underlying mechanisms of Gastrodia elata polysaccharides on dextran sulfate sodium-induced inflammatory bowel disease in mice：modulation of the gut microbiota and improvement of metabolic disorders[J]. Int J Biol Macromol，2023，248：125919.

蒯欢欢，于骏娣，李灿涛，等. 基于网络药理学探讨土茯苓防治炎症性肠病的作用机制[J]. 现代药物与临床，2023，38（6）：1352-1359.

KUAI H H，YU J D，LI C T，et al. Mechanism of Smilax glabra in treatment of inflammatory bowel disease based on network pharmacology[J]. Drugs Clin，2023，38（6）：1352-1359.

WU J J，DENG Y，ZHANG X，et al. Suchilactone inhibits the growth of acute myeloid leukemia by inactivating SHP2[J]. Pharm Biol，2022，60（1）：144-153.

霍敏峰，岳娟，董秋梅，等. 半夏泻心汤及其拆方改善炎症性肠病肠道免疫的潜在靶点及作用机制的网络药理学分析[J]. 包头医学院学报，2023，39（2）：62-72.

HUO M F，YUE J，DONG Q M，et al. Potential targets and mechanism of Banxia xiexin decoction and its disassembled prescriptions on improving intestinal immunity in patients with inflammatory bowel disease[J]. J Baotou Med Coll，2023，39（2）：62-72.

饶志红，杨文明，李祥，等. 肉苁蓉改善认知功能的化学成分及其作用机制研究[J]. 中国民族民间医药，2022，31（15）：56-60.

RAO Z H，YANG W M，LI X，et al. Study on the drug components and action mechanism of Cistanche for improving cognitive function[J]. Chin J Ethnomed Ethnopharmacy，2022，31（15）：56-60.

WANG J，ZHAO X Y，WANG Q Z，et al. FAM76B regulates PI3K/Akt/NF-κB-mediated M1 macrophage polarization by influencing the stability of PIK3CD mRNA[J]. Cell Mol Life Sci，2024，81（1）：107.

YE S H，ZUO B W，XU L N，et al. Inhibition of SHP2 by the small molecule drug SHP099 prevents lipopolysaccharide-induced acute lung injury in mice[J]. Inflammation，2023，46（3）：975-986.

徐琼，张恒，王辉. 基于EGFR介导的信号通路探讨中药活性成分抗肿瘤研究进展[J]. 中国实验方剂学杂志，2023，29（6）：246-253.

XU Q，ZHANG H，WANG H. Anti-tumor activity of Chinese medicine based on EGFR signaling pathway：a review[J]. Chin J Exp Tradit Med Formulae，2023，29（6）：246-253.

邵荣瑢，杨子，张文静，等. 茯苓酸缓解小鼠克罗恩病：基于抑制PI3K/AKT信号通路拮抗肠上皮细胞凋亡[J]. 南方医科大学学报，2023，43（6）：935-942.

SHAO R R，YANG Z，ZHANG W J，et al. Pachymic acid protects against Crohn’s disease-like intestinal barrier injury and colitis in mice by suppressing intestinal epithelial cell apoptosis via inhibiting PI3K/AKT signaling[J]. J South Med Univ，2023，43（6）：935-942.

DELGADO-RAMIREZ Y，BALTAZAR-PEREZ I，MARTINEZ Y，et al. STAT1 is required for decreasing accumulation of granulocytic cells via IL-17 during initial steps of colitis-associated cancer[J]. Int J Mol Sci，2021，22（14）：7695.

黄淑芸，许萍，洪宗元，等. 安石榴苷改善小鼠细菌性肠炎及调节肠道菌群的实验研究[J]. 中草药，2022，53（10）：3044-3052.

HUANG S Y，XU P，HONG Z Y，et al. Experimental study on improvement of bacterial enteritis and regulation of intestinal flora in mice by punicalagin[J]. Chin Tradit Herb Drugs，2022，53（10）：3044-3052.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Material basis and mechanism of Kazakh classic prescription Wuzdekh in the treatment of enteritis

Pharmacodynamic substances and mechanism of Chelidonii Herba-Corydalis Rhizoma against estrogen receptor-positive breast cancer

Study on the effects and mechanism of luteolin on osteogenic repair of bone defects

Identification of the chemical composition of Xiaoshi granules and study on its potential mechanism of the treatment of functional dyspepsia

Related Author

YANG Weijun

WANG Xue

HE Jiang

SHI Yuzhu

CHENG Bo

JIA Liping

ZOU Xiang

QU Zhongyuan

Related Institution

School of Food Science and Pharmacy， Xinjiang Agricultural University

Key Laboratory of Xinjiang Uygur Medicine， Xinjiang Institute of Materia Medica

Laboratory Ⅱ of Pharmacology， Xinjiang Institute of Materia Medica

Pharmaceutical Engineering Technology Research Center， Harbin University of Commerce

College of Pharmacy， Harbin University of Commerce

Address：8th Floor, Sihuan Building, No. 129 Daping Main Street, Yuzhong District, Chongqing, China Postal code：400042
Technical support is provided by Beijing Founder Electronics co., LTD 渝ICP备15012710号公网安备50010302001817
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰

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