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陈茉,文颖娟,杨俊超,吴倩,彭高强,仝武宁.基于网络药理学探究葛根治疗重症肌无力的潜在作用机制及实验验证[J].湖南中医药大学学报英文版,2021,41(11):1717-1725.[Click to copy
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| 基于网络药理学探究葛根治疗重症肌无力的潜在作用机制及实验验证 |
| 陈茉,文颖娟,杨俊超,吴倩,彭高强,仝武宁 |
| (陕西中医药大学, 陕西 咸阳 712046) |
| 摘要: |
| 目的 运用网络药理学探讨中药葛根治疗重症肌无力（myasthenia gravis，MG）的潜在作用机制，通过动物实验进行初步验证。方法 运用TCMSP筛选葛根主要活性成分与相关靶点信息；结合UniProt人类基因数据库，对活性成分进行蛋白质转化；筛选GeneCards数据库、Drugbank数据库、Therapeutic Target Database数据库中有关MG疾病靶点信息；通过STRING数据库、Metascape数据库对中药-疾病交集作用靶点进行蛋白互作网络分析；运用R语言对作用靶点进行基因本体GO与KEGG富集分析；采用动物实验对IL-4、TGF-β1、Bcl-2、Caspase-9等作用靶点进行验证。结果 共筛选出中药-疾病相关基因27个，涉及4种中药活性成分。蛋白互作网络分析得知IL-4、TGF-β1、Bcl-2、JUN、MAPK 14等可能是葛根治疗MG的重要靶点。KEGG分析结果表明，葛根治疗MG主要与APOPTOSIS、AGE-RAGE、P13K-Akt、Hepatitis B等多条信号通路有关。动物实验结果证实，葛根及其复方配伍通过减弱Bcl-2、升高Caspase-9表达，干预骨骼肌细胞凋亡，此外，EAMG大鼠血清中TGF-β1表达上调，AchR-ab、IL-4表达显著下降，验证了网络药理学的结果。结论 中药葛根治疗MG的主要生物学机制可能与多种因子及信号通路密切相关，葛根及其复方配伍能够通过影响IL-4、TGF-β1、Bcl-2、Caspase-9表达干预MG的治疗。 |
| 关键词: 葛根 重症肌无力 网络药理学 信号通路 细胞凋亡 大鼠 |
| DOI：10.3969/j.issn.1674-070X.2021.11.012 |
| Received:June 04, 2021 |
| 基金项目:国家重点研发计划课题（2017YFC1703506）；国家自然科学基金项目（81202642）；第四批全国中医（临床、基础）优秀人才研修项目[国中医药人教发〔2017〕24号]；陕西省科学技术厅项目（2017SF-323）。 |
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| Potential Mechanism and Preliminary Verification of Gegen (Puerariae Lobatae Radix) and its Compound Compatibility in the Treatment of Myasthenia Gravisabout Based on Network Pharmacology |
| CHEN Mo,WEN Yingjuan,YANG Junchao,WU Qian,PENG Gaoqiang,TONG Wuning |
| (Shaanxi University Of Chinese Medicine, Xianyang, Shaanxi 712046, China) |
| Abstract: |
| Objective To explore the potential mechanism of Chinese medicine Gegen (Puerariae Lobatae Radix) in the treatment of myasthenia gravis (MG) by using network pharmacology, and to conduct preliminary verification through animal experiments. Methods TCMSP was used to screen the main active ingredients and related target information of Gegen (Puerariae Lobatae Radix); combined with the UniProt human gene database, the active ingredients were transformed into proteins; the GeneCards database, the Drugbank database, and the Therapeutic Target Database (TTD) were searched and screened for related MG disease targets information; protein-protein interaction (PPI) network of the traditional Chinese medicine-disease interaction target was analyzed by the STRING database and Metascape database; the R language was used to analyze the target point of gene ontology GO and KEGG enrichment; the animal experiments were used to verify IL-4, TGF-β1, Bcl-2, Caspase-9 and other targets. Results A total of 27 Chinese medicine-disease-related genes were screened, involving 4 active ingredients of Chinese medicine. PPI network topology analysis revealed that IL-4, TGF-β1, Bcl-2, JUN, MAPK 14, etc. may be important targets for Gegen (Puerariae Lobatae Radix) in the treatment of MG. KEGG analysis results showed that the treatment of MG by Gegen (Puerariae Lobatae Radix) is mainly related to multiple signaling pathways such as APOPTOSIS, AGE-RAGE, P13K-Akt, and Hepatitis B. Animal experiment results confirmed that Gegen (Puerariae Lobatae Radix) and its compound compatibility can interfere skeletal muscle cell apoptosis by attenuating Bcl-2 and increasing Caspase-9 expression. In addition, the expression of TGF-β1 in the serum of EAMG rats was up-regulated, and the expression of acetylcholine receptor antibody and IL-4 significantly declined, verified the reliability of network pharmacology. Conclusion The main biological mechanism of the traditional Chinese medicine Gegen (Puerariae Lobatae Radix) in treating MG may be closely related to a variety of factors and signal pathways. Gegen (Puerariae Lobatae Radix) and its compound compatibility can interfere the treatment of MG by affecting the expression of IL-4, TGF-β, Bcl-2 and Caspase-9. |
| Key words: Gegen (Puerariae Lobatae Radix) myasthenia gravis network pharmacology signal pathway apoptosis rat |
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