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基于网络药理学探究玉屏风散增强免疫力的作用机制
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Abstract:
目的:基于网络药理学探讨玉屏风散增强免疫力的活性化合物及作用机制。方法:通过中药系统药理学数据库与分析平台(Traditional Chinese medicine systems pharmacology database and analysis platform, TCMSP)检索玉屏风散组方中黄芪、防风、白术的化学成分,设置筛选条件得到有效活性化合物及对应靶点,通过UniProt数据库对靶点进行标准化处理;通过GeneCards数据库和在线人类孟德尔遗传数据库(OMIM)检索与免疫相关的靶点并进行相应筛选;使用Venny2.1软件将药物靶点和与免疫相关的靶点导入,绘制韦恩图以获得交集靶点,使用Cytoscape3.9.1绘制“药物–疾病–活性化合物–靶点”交互关系网络图;将交集靶点导入String数据库,绘制蛋白相互作用(PPI)网络,并在Cytoscape3.9.1中对PPI网络进行优化处理以筛选出核心靶点;使用Metascape数据库对核心靶点进行GO功能和KEGG通路的富集分析,并在Bioinformatics平台上对分析结果进行可视化处理。结果:得到了44种玉屏风散的活性化合物和215种经统一标准化命名的靶点,免疫相关靶点7220个,交集靶点184个,核心靶点38个;GO分子功能(MF)有63个条目,GO生物学过程(BP)有1059个条目,GO细胞组分(CC)有34个条目。此外,KEGG Pathway富集分析确定了171条通路。结论:玉屏风散可能通过介导氧化应激反应、炎症反应,RNA聚合酶II转录调节,DNA结合转录因子结合等作用于IL-17、AGE-RAGE、PI3K-Akt信号通路,调控AKT1、TNF、IL6等靶点,发挥增强免疫力的作用。
Objective: Based on network pharmacology, this study aims to explore the active compounds and mechanisms of Yu Ping Feng San in enhancing immune function. Methods: The chemical components of Huang Qi, Fang Feng, and Bai Zhu in the formula of Yu Ping Feng San were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Filtering criteria were set to obtain effective active compounds and their corresponding targets. The targets were standardized using the UniProt database. Immune-related targets were retrieved from the Gene Cards database and the Online Mendelian Inheritance in Man database (OMIM), and corresponding screening was performed. The drug targets and immune-related targets were imported into Venny2.1 software to obtain the intersection targets, and the “drug-disease-active compound-target” interaction network was visualized using Cytoscape3.9.1. The intersection targets were imported into the STRING database to construct a protein-protein interaction (PPI) network, and the PPI network was optimized using Cytoscape3.9.1 to screen for core targets. The core targets were subjected to enrichment analysis of Gene Ontology (GO) functions and KEGG pathways using the Metascape database, and the analysis results were visualized using the Bioinformatics platform. Results: A total of 44 active compounds of Yu Ping Feng San and 215 targets with standardized names were obtained. Among them, there were 7220 immune-related targets, 184 intersection targets, and 38 core targets. GO analysis showed 63 entries for molecular function (MF), 1059 entries for
[1] | 赵子申, 高雅丽, 刘文芳, 等. 玉屏风散现代药理学研究及皮肤科研究进展[J]. 中国中西医结合皮肤性病学杂志, 2018, 17(2): 187-189. |
[2] | 梁月晴, 解建平, 都宏. 玉屏风散治疗呼吸系统疾病研究进展[J]. 中国中医药信息杂志, 2001, 8(5): 23-24. |
[3] | 李红念, 梅全喜, 戴卫波, 等. 玉屏风散的临床应用与药理作用研究进展[J]. 广州中医药大学学报, 2016, 33(2): 284-287. |
[4] | 张宇欣, 刘魏魏, 杨娟, 等. 基于网络药理学和分子对接探讨常见酚酸提高机体免疫力的作用机制[J]. 食品工业科技, 2023, 44(2): 29-40. |
[5] | 赵晓东, 杨锡强. 应当合理使用免疫调节剂[J]. 中华儿科杂志, 2006, 44(6): 401-402. |
[6] | Abdel-Hamid, Z.D. and Thalij, K.M. (2020) The Effects of Oral Dosage of Glutathione and Some Biological Agents on Immunity and Oxidative Stress Parameters in Male Rats Induced with Immunosuppression. EurAsian Journal of Biosciences, 14, 2933-2939. |
[7] | Perrigoue, J.G., Zaph, C., Guild, K., Du, Y. and Artis, D. (2009) IL-31-IL-31R Interactions Limit the Magnitude of Th2 Cytokine-Dependent Immunity and Inflammation Following Intestinal Helminth Infection. The Journal of Immunology, 182, 6088-6094. https://doi.org/10.4049/jimmunol.0802459 |
[8] | 胡妮娜, 张晓娟. 黄芪的化学成分及药理作用研究进展[J]. 中医药信息, 2021, 38(1): 76-82. |
[9] | 曹思思, 史磊, 孙佳琳, 等. 防风的化学成分及药理作用研究进展[J]. 现代中药研究与实践, 2021, 35(1): 95-102. |
[10] | 张晓娟, 左冬冬. 白术化学成分及药理作用研究新进展[J]. 中医药信息, 2018, 35(6): 101-106. |
[11] | 张磊. 玉屏风散免疫作用机制的研究[D]: [博士学位论文]. 成都: 成都中医药大学, 2006. |
[12] | 柳永青. 中成药玉屏风散研究进展[J]. 中外医疗, 2009, 28(34): 178. |
[13] | 张静, 王凯旋, 祝骁涛, 等. 中西医结合提高小儿免疫力改善反复呼吸道感染的临床研究[J]. 中华中医药学刊, 2015, 33(6): 1477-1479. |
[14] | 李晓琳. 玉屏风散对于单板U型场地项目运动员免疫能力影响的临床研究[J]. 南京体育学院学报(自然科学版), 2014, 13(1): 31-33, 39. |
[15] | 李雪嫣, 张李峰, 桂曼曼, 等. 复方玉屏风散对小鼠细胞免疫力的增强作用研究[J]. 西部中医药, 2013, 36(8): 11-14. |
[16] | 田瑞雪, 孙耀宗, 姚有昊, 等. 槲皮素对免疫低下小鼠免疫功能的影响[J]. 中国现代医药杂志, 2019, 21(9): 13-16. |
[17] | 刘晟文, 刘建英. 槲皮素药理学作用的研究进展[J]. 中华肺部疾病杂志(电子版), 2020, 13(1): 104-106. |
[18] | 肖炜明, 卜平, 龚卫娟. 汉黄芩素抗肿瘤和免疫调节作用的研究进展[J]. 中国中药杂志, 2014, 39(16): 3004-3009. |
[19] | 吴绮丽, 袁晓峰, 陈静柔, 等. 汉黄芩素诱导中性粒细胞凋亡保护免疫性肝损伤[J]. 热带医学杂志, 2021, 21(12): 1512-1516. |
[20] | 肖炜明. 汉黄芩素对胃癌生长及细胞免疫功能影响的研究[D]: [博士学位论文]. 扬州: 扬州大学, 2013. |
[21] | 慕静静, 曾耀英, 黄秀艳, 等. 山奈酚对小鼠T淋巴细胞体外活化、增殖和细胞周期的影响[J]. 细胞与分子免疫学杂志, 2009, 25(12): 1106-1108. |
[22] | 张健萱. 基于NF-κB信号通路探讨小青龙汤、麻黄细辛附子汤合玉屏风散对变应性鼻炎大鼠NF-κBp65, p-CREB及AQP5表达的影响[D]: [硕士学位论文]. 沈阳: 辽宁中医药大学, 2023. |
[23] | 赵凯. 基于“天人相应”理论和网络药理学探讨褪黑素和玉屏风散对小鼠免疫功能的影响[D]: [硕士学位论文]. 北京: 北京中医药大学, 2020. |
[24] | Ai, K., Yan, J., Li, K., Li, C., Zhang, Y., Liang, W., et al. (2021) Akt1/mTORC1 Signaling Modulates Adaptive Immune Response of Nile Tilapia by Promoting Lymphocyte Activation and Proliferation. Developmental & Comparative Immunology, 119, Article 104042. https://doi.org/10.1016/j.dci.2021.104042 |
[25] | Maroulakou, I.G., Oemler, W., Naber, S.P. and Tsichlis, P.N. (2007) Akt1 Ablation Inhibits, Whereas Akt2 Ablation Accelerates, the Development of Mammary Adenocarcinomas in Mouse Mammary Tumor Virus (MMTV)-ErbB2/Neu and MMTV-Polyoma Middle T Transgenic Mice. Cancer Research, 67, 167-177. https://doi.org/10.1158/0008-5472.can-06-3782 |
[26] | Green, B.D., Jabbour, A.M., Sandow, J.J., Riffkin, C.D., Masouras, D., Daunt, C.P., et al. (2013) Akt1 Is the Principal Akt Isoform Regulating Apoptosis in Limiting Cytokine Concentrations. Cell Death & Differentiation, 20, 1341-1349. https://doi.org/10.1038/cdd.2013.63 |
[27] | 孙冠聪, 焦丹, 谢忠奎, 等. PI3K/AKT通路在动物葡萄糖代谢中的研究进展[J]. 生命科学, 2021, 33(5): 653-666. |