|
|
基于网络药理学的绞股蓝治疗急性肺损伤疗效分析
|
Abstract:
目的：基于网络药理学研究绞股蓝治疗急性肺损伤(acute lung injury, ALI)的有效成分和潜在靶点。方法：从中药系统药理学数据库和分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, TCMSP)中获取绞股蓝的活性成分、相关靶点和相关靶基因。同时，通过OMIM数据库、GeneCards数据库和Therapeutic Target数据库获取ALI靶基因信息。文氏图用于显示绞股蓝和ALI的共同靶点。使用Cytoscape 3.7.2构建药物成分靶点疾病网络图，并从STRING数据库获得蛋白–蛋白相互作用(Protein-Protein Interaction Networks, PPI)网络。同时，使用生物信息学网站平台进行基因本体富集分析和KEGG (Kyoto Encyclopedia of Genes and Genomes)通路富集分析以揭示该机制。结果：结果分为三个阵营：成分、靶点和途径。在成分方面，发现绞股蓝的15种活性成分在细胞膜、细胞质和细胞核中具有生物活性，其中槲皮素、鼠李素和异岩藻甾醇是主要活性成分。共发现155个靶点，其中134个主要靶点和ALI共同拥有(尤其是AKT1 (Protein Kinase Bα)、TP53 (tumor protein p53)、TNF (tumor necrosis factor)、IL-6 (Interleukin-6)、VEGFA (Vascular endothelial growth factor A)、CASP3 (Caspase-3)、IL-1B (Interleukin-1B)、HIF-1A (hypoxia inducible factor-1A)、EGFR (Epidermal growth factor receptor)和PTGS2 (Prostaglandin-Endoperoxide Synthase 2))有助于ALI的治疗。此外，绞股蓝治疗ALI的主要途径是PI3K-Akt (Phosphatidylinositol-3-kinase)信号通路、脂质和动脉粥样硬化、糖尿病并发症中的AGE-RAGE (advanced glycosylation end products-receptor of AGEs)信号通路、HIF-1信号通路、肿瘤和感染相关通路。结论：由于绞股蓝的多组分、多靶点和多通道功能，本研究通过网络药理学初步揭示了绞股蓝治疗ALI的潜在调节网络。为后续的实验研究和临床应用提供了理论依据。
Objective: To study the active components and potential targets of Gynostemma pentaphyllum in the treatment of acute lung injury (ALI) based on network pharmacology. Methods: The active components, related targets and related target genes of Gynostemma pentaphyllum were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). At the same time, ALI target gene information is obtained through OMIM database, GeneCards database and Therapeutic Target database. Venn diagram is used to show the common targets of Gynostemma pentaphyllum and ALI. Use Cytoscape 3.7.2 to construct the target disease network diagram of drug components, and obtain the protein-protein interaction networks (PPI) network from STRING database. At the same time, the bioinformatics website platform was used for gene ontology enrichment analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis to reveal the mechanism. Results: The results were divided into three camps: component, target and pathway. In terms of components, it was found that 15 active components of Gynostemma pentaphyllum had biological activities in the cell membrane, cytoplasm and nucleus, among which quercetin, rhamnolicin and isofucosterol were the main active components. A total of 155 targets were found, 134 of which were jointly owned by ALI (especially AKT1 (Protein Kinase Bα), TP53 (tumor protein p53), TNF (tumor neurosis
| [1] | Shaw, T.D., McAuley, D.F. and O’Kane, C.M. (2019) Emerging Drugs for Treating the Acute Respiratory Distress Syndrome. Expert Opinion on Emerging Drugs, 24, 29-41. https://doi.org/10.1080/14728214.2019.1591369 |
| [2] | Zhang, Y., Zhang, H., Li, S., et al. (2022) Metformin Alleviates LPS-Induced Acute Lung Injury by Regulating the SIRT1/NF-κB/NLRP3 Pathway and Inhibiting Endothelial Cell Pyroptosis. Frontiers in Pharmacology, 13, Article ID: 801337. https://doi.org/10.3389/fphar.2022.801337 |
| [3] | Reilly, J.P., Calfee, C.S. and Christie, J.D. (2019) Acute Respiratory Distress Syndrome Phenotypes, 2019. Thieme Medical Publishers, New York. https://doi.org/10.1055/s-0039-1684049 |
| [4] | Fan, E., Brodie, D. and Slutsky, A.S. (2018) Acute Respiratory Distress Syndrome: Advances in Diagnosis and Treatment. JAMA, 319, 698-710. https://doi.org/10.1001/jama.2017.21907 |
| [5] | Matthay, M.A., Zemans, R.L., Zimmerman, G.A., et al. (2019) Acute Respiratory Distress Syndrome. Nature Reviews Disease Primers, 5, 1-22. https://doi.org/10.1038/s41572-019-0069-0 |
| [6] | Fan, W.-J., et al. (2022) Research Progress on Mechanism of Jiegeng Decoction and Its Active Components in Treatment of Acute Lung Injury. Chinese Traditional and Herbal Drugs, 53, 1230-1239. |
| [7] | 张琼, 黄晓飞, 翟文海. 绞股蓝总皂苷对2型糖尿病小鼠糖脂代谢水平及肝脏自噬基因表达的影响[J]. 时珍国医国药, 2018, 29(2): 3. |
| [8] | Lu, Y.-L., et al. (2018) Hypolipemic Mechanism of Saponins from Gynostemma pentaphylla Based on Analysis of Bile Acids. Natural Product Research and Development, 30, 1143. |
| [9] | Xing, S., Liu, L., Zu, M., et al. (2019) Inhibitory Effect of Damulin B from Gynostemma pentaphyllum on Human Lung Cancer Cells. Planta Medica, 85, 394-405. https://doi.org/10.1055/a-0810-7738 |
| [10] | Zhang, X., Shi, G., Wu, X., et al. (2020) Gypensapogenin H from Hydrolyzate of Total Gynostemma pentaphyllum Saponins Induces Apoptosis in Human Breast Carcinoma Cells. Natural Product Research, 34, 1642-1646.
https://doi.org/10.1080/14786419.2018.1525370 |
| [11] | 方磊涵, 毕玉霞, 王振, 等. 绞股蓝多糖对猪瘟弱毒疫苗免疫效果的影响[J]. 中兽医医药杂志, 2018, 37(1): 58-60. |
| [12] | Zhou, W.C. (2018) Research on Extraction and Anti-Inflammatory Activity of New Saponins from Gynostemma pentaphyllum Seeds. Yunnan Chemical Industry, 45, 34-37. |
| [13] | 南瑛, 张薇, 常晋瑞, 等. 绞股蓝皂苷通过Nrf2/NF-κB信号通路发挥抗小鼠急性酒精性肝损伤作用[J]. 中国药理学通报, 2019, 35(1): 40-45. |
| [14] | 彭心怡, 倪锴文, 丁阳阳, 等. 绞股蓝水提醇沉液抗川楝子致小鼠慢性肝损伤的实验研究[J]. 浙江中西医结合杂志, 2018, 28(10): 818-820. |
| [15] | 孙立峰, 郭华, 孟剑锋, 等. 绞股蓝总黄酮通过抑制氧化应激反应抗心肌缺血保护作用的研究[J]. 中华中医药学刊, 2018, 36(10): 2513-2515. |
| [16] | 宋囡, 杨芳, 曹慧敏, 等. 绞股蓝总甙调控mTOR/ULK1通路对ApoE-/-小鼠动脉粥样硬化的影响[J]. 中国动脉硬化杂志, 2018, 26(2): 127-132. |
| [17] | 杜楠, 王璐, 白鸽, 等. 绞股蓝籽油食品安全毒理学评价及抗衰老研究[J]. 西北农林科技大学学报: 自然科学版, 2018, 46(5): 131-140, 148. |
| [18] | Nguyen, N.-H., et al. (2021) Triterpenoids from the Genus Gynostemma: Chemistry and Pharmacological Activities. Journal of Ethnopharmacology, 268, Article ID: 113574. https://doi.org/10.1016/j.jep.2020.113574 |
| [19] | Jin, J., Chen, B., Zhan, X., et al. (2021) Network Pharmacology and Molecular Docking Study on the Mechanism of Colorectal Cancer Treatment Using Xiao-Chai-Hu-Tang. PLOS ONE, 16, e252508.
https://doi.org/10.1371/journal.pone.0252508 |
| [20] | Zhou, Y., Zhou, B., Pache, L., et al. (2019) Metascape Provides a Biologist-Oriented Resource for the Analysis of Systems-Level Datasets. Nature Communications, 10, Article No. 1523. https://doi.org/10.1038/s41467-019-09234-6 |
| [21] | Ji, X., Shen, Y. and Guo, X. (2018) Isolation, Structures, and Bioactivities of the Polysaccharides from Gynostemma pentaphyllum (Thunb.) Makino: A Review. BioMed Research International, 2018, Article ID: 6285134.
https://doi.org/10.1155/2018/6285134 |
| [22] | Fan, D. (2017) Research Progress in Chemical Constituents and Pharmacological Activities of Gynostemma pentaphyllum. Chinese Pharmaceutical Journal, 52, 342-352. |
| [23] | 王玉荣. 壮药国虾薄(绞股蓝)黄酮及其肺损伤修复作用的研究[D]: [博士学位论文]. 北京: 中央民族大学, 2018. |
| [24] | Luo, T., Lu, Y., Yan, S., et al. (2020) Network Pharmacology in Research of Chinese Medicine Formula: Methodology, Application and Prospective. Chinese Journal of Integrative Medicine, 26, 72-80.
https://doi.org/10.1007/s11655-019-3064-0 |
| [25] | Zhang, Q., Guo, Y. and Zhang, D. (2022) Network Pharmacology Integrated with Molecular Docking Elucidates the Mechanism of Wuwei Yuganzi San for the Treatment of Coronary Heart Disease. Natural Product Communications, 17, 2006-2017. https://doi.org/10.1177/1934578X221093907 |
| [26] | Jiang, M., Lv, Z., Huang, Y., et al. (2022) Quercetin Alleviates Lipopolysaccharide-Induced Inflammatory Response in Bovine Mammary Epithelial Cells by Suppressing TLR4/NF-κB Signaling Pathway. Frontiers in Veterinary Science, 9, Article ID: 915726. https://doi.org/10.3389/fvets.2022.915726 |
| [27] | Ebokaiwe, A.P., Obasi, D.O. and Kalu, W.O. (2022) Abatement of Cyclophosphamide-Induced Splenic Immunosuppressive Indoleamine 2,3-Dioxygenase and Altered Hematological Indices in Wister Rats by Dietary Quercetin. Immunobiology, 227, Article ID: 152218. https://doi.org/10.1016/j.imbio.2022.152218 |
| [28] | Karancsi, Z., Kovács, D., Palkovicsné Pézsa, N., et al. (2022) The Impact of Quercetin and Its Methylated Derivatives 3-o-Methylquercetin and Rhamnazin in Lipopolysaccharide-Induced Inflammation in Porcine Intestinal Cells. Antioxidants, 11, 1265. https://doi.org/10.3390/antiox11071265 |
| [29] | He, D., Huang, J., Zhang, Z., et al. (2019) A Network Pharmacology-Based Strategy for Predicting Active Ingredients and Potential Targets of LiuWei DiHuang Pill in Treating Type 2 Diabetes Mellitus. Drug Design, Development and Therapy, 13, 3989. https://doi.org/10.2147/DDDT.S216644 |
| [30] | Zhang, L., Han, L., Wang, X., et al. (2021) Exploring the Mechanisms Underlying the Therapeutic Effect of Salvia Miltiorrhiza in Diabetic Nephropathy Using Network Pharmacology and Molecular Docking. Bioscience Reports, 41, BSR20203520. https://doi.org/10.1042/BSR20203520 |
| [31] | Zheng, W., Yan, Q., Ni, Y., et al. (2020) Examining the Effector Mechanisms of Xuebijing Injection on COVID-19 Based on Network Pharmacology. BioData Mining, 13, 1-23. https://doi.org/10.1186/s13040-020-00227-6 |
| [32] | Jin, Z., Li, M., Tang, L., et al. (2022) Protective Effect of Ulinastatin on Acute Lung Injury in Diabetic Sepsis Rats. International Immunopharmacology, 108, Article ID: 108908. https://doi.org/10.1016/j.intimp.2022.108908 |
| [33] | Burgos, R.A., Alarcón, P., Quiroga, J., et al. (2020) Andrographolide, an Anti-Inflammatory Multitarget Drug: All Roads Lead to Cellular Metabolism. Molecules, 26, 5. https://doi.org/10.3390/molecules26010005 |
| [34] | Yeung, Y.T., Aziz, F., Guerrero-Castilla, A., et al. (2018) Signaling Pathways in Inflammation and Anti-Inflammatory Therapies. Current Pharmaceutical Design, 24, 1449-1484. https://doi.org/10.2174/1381612824666180327165604 |
| [35] | Akiyama, Y., Miyakawa, J., O’Donnell, M.A., et al. (2022) Overexpression of HIF1α in Hunner Lesions of Interstitial Cystitis: Pathophysiological Implications. The Journal of Urology, 207, 635-646.
https://doi.org/10.1097/JU.0000000000002278 |
| [36] | Zhao, S., Gao, J., Li, J., et al. (2021) PD-L1 Regulates Inflammation in LPS-Induced Lung Epithelial Cells and Vascular Endothelial Cells by Interacting with the HIF-1α Signaling Pathway. Inflammation, 44, 1969-1981.
https://doi.org/10.1007/s10753-021-01474-3 |
| [37] | Chen, S., Wu, J., Yang, L., et al. (2022) Dexmedetomidine Leads to the Mitigation of Myocardial Ischemia/Reperfusion- Induced Acute Lung Injury in Diabetic Rats via Modulation of Hypoxia-Inducible Factor-1α. Brazilian Journal of Cardiovascular Surgery, 37, 370-379. https://doi.org/10.21470/1678-9741-2020-0591 |
| [38] | Tian, G., Gu, X., Bao, K., et al. (2021) Anti-Inflammatory Effects and Mechanisms of Pudilanantiphlogistic Oral Liquid. ACS Omega, 6, 34512-34524. https://doi.org/10.1021/acsomega.1c04797 |
| [39] | Chen, L., Deng, H., Cui, H., et al. (2018) Inflammatory Responses and Inflammation-Associated Diseases in Organs. Oncotarget, 9, 7204. https://doi.org/10.18632/oncotarget.23208 |
| [40] | Luo, J., Yang, C., Luo, X., et al. (2020) Chlorogenic Acid Attenuates Cyclophosphamide-Induced Rat Interstitial Cystitis. Life Sciences, 254, Article ID: 117590. https://doi.org/10.1016/j.lfs.2020.117590 |
| [41] | Sun, Z., Li, Q., Hou, R., et al. (2019) Kaempferol-3-O-Glucorhamnoside Inhibits Inflammatory Responses via MAPK and NF-κB Pathways in Vitro and in Vivo. Toxicology and Applied Pharmacology, 364, 22-28.
https://doi.org/10.1016/j.taap.2018.12.008 |
| [42] | Cai, X., Chen, Y., Xie, X., et al. (2019) Astaxanthin Prevents against Lipopolysaccharide-Induced Acute Lung Injury and Sepsis via Inhibiting Activation of MAPK/NF-κB. American Journal of Translational Research, 11, 1884. |
| [43] | Xu, M., Wang, C., Li, N., et al. (2019) Intraperitoneal Injection of Acetate Protects Mice against Lipopolysaccharide (LPS)-Induced Acute Lung Injury through Its Anti-Inflammatory and Anti-Oxidative Ability. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research, 25, 2278.
https://doi.org/10.12659/MSM.911444 |
| [44] | Zheng, J., Zhuo, J., Nie, J., et al. (2021) Phenylethanoid Glycosides From Callicarpa Kwangtungensis Chun Attenuate TNF-α-Induced Cell Damage by Inhibiting NF-κB Pathway and Enhancing Nrf2 Pathway in A549 Cells. Frontiers in Pharmacology, 12, Article ID: 693983. https://doi.org/10.3389/fphar.2021.693983 |
| [45] | Sahib, H.B., Kathum, O.A., Alanee, R.S., et al. (2022) The Anti-Cytokine Storm Activity of Quercetin Zinc and Vitamin C Complex. Advances in Virology, 2022, Article ID: 1575605. https://doi.org/10.1155/2022/1575605 |
| [46] | Sang, A., Wang, Y., Wang, S., et al. (2022) Quercetin Attenuates Sepsis-Induced Acute Lung Injury via Suppressing Oxidative Stress-Mediated ER Stress through Activation of SIRT1/AMPK Pathways. Cellular Signalling, 2022, Article ID: 110363. https://doi.org/10.1016/j.cellsig.2022.110363 |
