|
|
Bioprocess 2025
基于网络药理学和分子对接探究马铃薯调节高血压的作用机制
|
Abstract:
目的：探究马铃薯影响高血压的活性成分和可能作用机制。方法：在知网、万方、维普、TCMSP、PubChem、HERB、DisGeNET等数据库检索马铃薯的潜在活性成分、靶点以及高血压相关靶点。将交集靶点导入STRING和Cytoscape3.10.3软件中进行分析，并利用CytoHCA、CytoHubba和MCODE插件挖掘马铃薯影响高血压的核心基因。应用DAVID数据库进行GO和KEGG富集剖析，利用Auto Dock Tools-1.5.6和PyMOL软件进行分子对接和可视化分析。结果：得到马铃薯活性成分15个，化合物预测靶点578个，高血压靶点2687个，马铃薯活性成分和高血压交集靶点299个。拓扑学分析后得到9个马铃薯影响高血压的核心靶点蛋白。GO和KEGG富集分析显示涉及多个生物过程、细胞组分和分子功能。关键信号通路包含GAPDH、MTOR、HIF1A、BCL2、AKT1和STAT3等。核心活性成分包括天竺葵色素(Pelargonidin)、矢车菊色素(Cyanidin)、芍药色素(Peonidin)、飞燕草色素(Delphinidin)和牵牛花色素(Petunidin)。分子对接结果提示活性成分与作用靶点能稳定结合，特别是GAPDH、MTOR和HIF1A与5种活性成分的结合能都很低，提示马铃薯活性成分有可能通过调节相关信号通路影响高血压。结论：本研究通过网络药理学分析和分子对接发现了马铃薯影响高血压的关键活性成分和核心作用靶点，花色苷对GAPDH和mTOR等靶点的调节值得深入研究。
Objective: To explore the active ingredients and possible mechanisms of potatoes regulating hypertension. Method: Retrieve potential active ingredients, targets, and hypertension related targets of potatoes from databases such as CNKI, Wanfang, VIP, TCMSP, PubChem, HERB, and DisGeNET. Import the intersection targets into STRING and Cytoscape3.10.3 software for analysis, and use CytoHCA, CytoHubba, and MCODE plugins to explore the core genes for potato affecting hypertension. Perform GO and KEGG enrichment analysis using DAVID database, and perform molecular docking and visualization analysis using Auto Dock Tools-1.5.6 and PyMOL software. Results: 15 active ingredients were obtained for potatoes, 578 predicted targets for bioactive compounds, 2687 targets for hypertension, and 299 intersecting targets between potato active ingredients and hypertension. After topological analysis, 9 core target proteins affecting hypertension in potatoes were identified. GO and KEGG enrichment analysis showed involvement in multiple biological processes, cellular components, and molecular functions. The key signaling pathways include GAPDH, MTOR, HIF1A, BCL2, AKT1, and STAT3. The core active ingredients include Pelargonidin, Cyanidin, Peonidin, Delphinidin, and Petunidin. The molecular docking results indicate that the active ingredients can stably bind to the target, especially GAPDH, MTOR, and HIF1A, which have low binding energies with the five active ingredients. This suggests that potato active ingredients may affect hypertension by regulating related signaling pathways. Conclusion: Through network pharmacology analysis and molecular docking, this study discovered the key active ingredients and core targets of potato affecting hypertension. The regulation of anthocyanins on targets such as GAPDH and mTOR deserves further investigation.
| [1] | Zhou, B., Perel, P., Mensah, G.A. and Ezzati, M. (2021) Global Epidemiology, Health Burden and Effective Interventions for Elevated Blood Pressure and Hypertension. Nature Reviews Cardiology, 18, 785-802. https://doi.org/10.1038/s41569-021-00559-8 |
| [2] | Wang, J., Zhang, W., Li, Y. and Liu, L. (2023) Hypertension in China: Epidemiology and Treatment Initiatives. Nature Reviews Cardiology, 20, 531-545. https://doi.org/10.1038/s41569-022-00829-z |
| [3] | Zhou, B., Carrillo-Larco, R.M., Danaei, G., Riley, L.M., Paciorek, C.J., Stevens, G.A., et al. (2021) Worldwide Trends in Hypertension Prevalence and Progress in Treatment and Control from 1990 to 2019: A Pooled Analysis of 1201 Population-Representative Studies with 104 Million Participants. The Lancet, 398, 957-980. https://doi.org/10.1016/s0140-6736(21)01330-1 |
| [4] | Sayer, M., Webb, D.J. and Dhaun, N. (2025) Novel Pharmacological Approaches to Lowering Blood Pressure and Managing Hypertension. Nature Reviews Cardiology. https://doi.org/10.1038/s41569-025-01131-4 |
| [5] | 黄金连, 周立红. 环境营养学研究进展[J]. 食品与营养科学, 2025, 14(1): 101-109. |
| [6] | Liu, B., Gu, W., Yang, Y., Lu, B., Wang, F., Zhang, B., et al. (2021) Promoting Potato as Staple Food Can Reduce the Carbon-Land-Water Impacts of Crops in China. Nature Food, 2, 570-577. https://doi.org/10.1038/s43016-021-00337-2 |
| [7] | Borgi, L., Rimm, E.B., Willett, W.C. and Forman, J.P. (2016) Potato Intake and Incidence of Hypertension: Results from Three Prospective US Cohort Studies. BMJ, 353, i2351. https://doi.org/10.1136/bmj.i2351 |
| [8] | Huang, M., Zhuang, P., Jiao, J., Wang, J., Chen, X. and Zhang, Y. (2019) Potato Consumption Is Prospectively Associated with Risk of Hypertension: An 11.3-Year Longitudinal Cohort Study. Clinical Nutrition, 38, 1936-1944. https://doi.org/10.1016/j.clnu.2018.06.973 |
| [9] | Tsai, B.C., Hsieh, D.J., Lin, W., Tamilselvi, S., Day, C.H., Ho, T., et al. (2020) Functional Potato Bioactive Peptide Intensifies NRF2-Dependent Antioxidant Defense against Renal Damage in Hypertensive Rats. Food Research International, 129, Article ID: 108862. https://doi.org/10.1016/j.foodres.2019.108862 |
| [10] | Su, Y., Liu, X., Jiang, B., He, H., Li, F., Li, X., et al. (2024) Potato Intake and the Risk of Overweight/Obesity, Hypertension, Diabetes, and Cardiovascular Disease: A Systematic Review and Meta-Analysis of Observational Studies. Nutrition Reviews, 83, 466-478. https://doi.org/10.1093/nutrit/nuae159 |
| [11] | Cheng, L., Wang, N., Bao, Z., Zhou, Q., Guarracino, A., Yang, Y., et al. (2025) Leveraging a Phased Pangenome for Haplotype Design of Hybrid Potato. Nature. https://doi.org/10.1038/s41586-024-08476-9 |
| [12] | Pihlanto, A., Akkanen, S. and Korhonen, H.J. (2008) Ace-Inhibitory and Antioxidant Properties of Potato (Solanum tuberosum). Food Chemistry, 109, 104-112. https://doi.org/10.1016/j.foodchem.2007.12.023 |
| [13] | 史佳文, 潘峰, 陈若男, 石瑛. 不同马铃薯品种块茎钾含量与相关生理特性的钾素响应度差异[J]. 华北农学报, 2019, 34(S1): 78-84. |
| [14] | Tian, J., Chen, J., Lv, F., Chen, S., Chen, J., Liu, D., et al. (2016) Domestic Cooking Methods Affect the Phytochemical Composition and Antioxidant Activity of Purple-Fleshed Potatoes. Food Chemistry, 197, 1264-1270. https://doi.org/10.1016/j.foodchem.2015.11.049 |
| [15] | 周立红. 烹饪医学学科发展历程与思路研究[J]. 食品与营养科学, 2024, 13(1): 133-142. |
| [16] | Vinson, J.A., Demkosky, C.A., Navarre, D.A. and Smyda, M.A. (2012) High-Antioxidant Potatoes: Acute in Vivo Antioxidant Source and Hypotensive Agent in Humans after Supplementation to Hypertensive Subjects. Journal of Agricultural and Food Chemistry, 60, 6749-6754. https://doi.org/10.1021/jf2045262 |
| [17] | Zhou, A.L. and Ward, R.E. (2024) Dietary Milk Phospholipids Increase Body Fat and Modulate Gut Permeability, Systemic Inflammation, and Lipid Metabolism in Mice. Journal of Dairy Science, 107, 10190-10202. https://doi.org/10.3168/jds.2024-25235 |
| [18] | 邢金月, 杨梦平, 翟玲侠, 等. 彩色马铃薯花色苷及其生理活性的研究进展[J/OL]. 分子植物育种: 1-10. https://link.cnki.net/urlid/46.1068.S.20240828.1353.002, 2024-08-29. |
| [19] | 吉米丽汗∙司马依, 买买提明∙努尔买买提, 艾尼瓦尔∙吾买尔, 等. 基于ADME和“Lipinski规则”的金叶败毒颗粒辅助治疗新型冠状病毒肺炎的活性成分研究[J]. 天然产物研究与开发, 2020, 32(10): 1629-1636. |
| [20] | 张玉娟. 基于网络药理学和分子对接法探讨增液汤治疗功能性便秘的作用机制[D]: [硕士学位论文]. 咸阳: 陕西中医药大学, 2023. |
| [21] | 冯译. 基于网络药理学和分子对接探讨眩晕灵治疗眩晕病的作用机制[D]: [硕士学位论文]. 咸阳: 陕西中医药大学, 2023. |
| [22] | 张彤, 覃姝瑜, 周立红, 等. 基于网络药理学研究楤木多糖影响痛风的分子机制[J]. 壮瑶药研究, 2023(3): 235-238. |
| [23] | Stanciu, S.M., Jinga, M., Miricescu, D., Stefani, C., Nica, R.I., Stanescu-Spinu, I., et al. (2024) mTOR Dysregulation, Insulin Resistance, and Hypertension. Biomedicines, 12, Article 1802. https://doi.org/10.3390/biomedicines12081802 |
| [24] | Zhang, Z., Tang, J., Song, J., Xie, M., Liu, Y., Dong, Z., et al. (2022) Elabela Alleviates Ferroptosis, Myocardial Remodeling, Fibrosis and Heart Dysfunction in Hypertensive Mice by Modulating the IL-6/STAT3/GPX4 Signaling. Free Radical Biology and Medicine, 181, 130-142. https://doi.org/10.1016/j.freeradbiomed.2022.01.020 |
| [25] | Tuo, Y., Lu, X., Tao, F., Tukhvatshin, M., Xiang, F., Wang, X., et al. (2024) The Potential Mechanisms of Catechins in Tea for Anti-Hypertension: An Integration of Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation. Foods, 13, Article 2685. https://doi.org/10.3390/foods13172685 |
| [26] | Li, Z., Hu, X., Wan, J., Yang, J., Jia, Z., Tian, L., et al. (2021) The Alleles of AGT and HIF1A Gene Affect the Risk of Hypertension in Plateau Residents. Experimental Biology and Medicine, 247, 237-245. https://doi.org/10.1177/15353702211055838 |
| [27] | Wang, J., Yu, X., Cao, X., Tan, L., Jia, B., Chen, R., et al. (2023) GAPDH: A Common Housekeeping Gene with an Oncogenic Role in Pan-cancer. Computational and Structural Biotechnology Journal, 21, 4056-4069. https://doi.org/10.1016/j.csbj.2023.07.034 |
| [28] | Tan, R., Li, J., Peng, X., Zhu, L., Cai, L., Wang, T., et al. (2013) GAPDH Is Critical for Superior Efficacy of Female Bone Marrow-Derived Mesenchymal Stem Cells on Pulmonary Hypertension. Cardiovascular Research, 100, 19-27. https://doi.org/10.1093/cvr/cvt165 |
| [29] | Zhang, X., Zhou, Y. and Zhang, H. (2024) Clinical Significance of HIF-1α, ET-1, and NO as Biomarkers in Chronic Obstructive Pulmonary Disease Patients with Pulmonary Hypertension. Biomolecules and Biomedicine. https://doi.org/10.17305/bb.2024.11078 |
| [30] | Rodríguez-Martínez, B., Gullón, B. and Yáñez, R. (2021) Identification and Recovery of Valuable Bioactive Compounds from Potato Peels: A Comprehensive Review. Antioxidants, 10, 1630. https://doi.org/10.3390/antiox10101630 |
| [31] | Sirover, M.A. (2011) On the Functional Diversity of Glyceraldehyde-3-Phosphate Dehydrogenase: Biochemical Mechanisms and Regulatory Control. Biochimica et Biophysica Acta (BBA)—General Subjects, 1810, 741-751. https://doi.org/10.1016/j.bbagen.2011.05.010 |
| [32] | Colell, A., Green, D.R. and Ricci, J. (2009) Novel Roles for GAPDH in Cell Death and Carcinogenesis. Cell Death & Differentiation, 16, 1573-1581. https://doi.org/10.1038/cdd.2009.137 |
| [33] | Zhou, A.L. and Ward, R.E. (2024) Dietary Milk Polar Lipids Modulate Gut Barrier Integrity and Lipid Metabolism in C57BL/6J Mice during Systemic Inflammation Induced by Escherichia Coli Lipopolysaccharide. Journal of Dairy Science, 107, 7578-7593. https://doi.org/10.3168/jds.2024-24759 |
| [34] | Liao, Y., Dong, S., Kiyama, R., Cai, P., Liu, L. and Shen, H. (2013) Flos Lonicerae Extracts and Chlorogenic Acid Protect Human Umbilical Vein Endothelial Cells from the Toxic Damage of Perfluorooctane Sulphonate. Inflammation, 36, 767-779. https://doi.org/10.1007/s10753-013-9603-5 |
| [35] | Nie, X., Dai, Y., Tan, J., Chen, Y., Qin, G., Mao, W., et al. (2017) α-Solanine Reverses Pulmonary Vascular Remodeling and Vascular Angiogenesis in Experimental Pulmonary Artery Hypertension. Journal of Hypertension, 35, 2419-2435. https://doi.org/10.1097/hjh.0000000000001475 |
| [36] | Choi, S., Choi, Y., Choi, Y., Kim, S., Jang, J. and Park, T. (2013) Piperine Reverses High Fat Diet-Induced Hepatic Steatosis and Insulin Resistance in Mice. Food Chemistry, 141, 3627-3635. https://doi.org/10.1016/j.foodchem.2013.06.028 |
| [37] | Waypa, G.B., Osborne, S.W., Marks, J.D., Berkelhamer, S.K., Kondapalli, J. and Schumacker, P.T. (2013) Sirtuin 3 Deficiency Does Not Augment Hypoxia-Induced Pulmonary Hypertension. American Journal of Respiratory Cell and Molecular Biology, 49, 885-891. https://doi.org/10.1165/rcmb.2013-0191oc |
| [38] | Chao, P., Huang, Y. and Hsieh, W. (2013) Inhibitive Effect of Purple Sweet Potato Leaf Extract and Its Components on Cell Adhesion and Inflammatory Response in Human Aortic Endothelial Cells. Cell Adhesion & Migration, 7, 237-245. https://doi.org/10.4161/cam.23649 |
| [39] | Lv, C., Kong, H., Dong, G., Liu, L., Tong, K., Sun, H., et al. (2014) Antitumor Efficacy of α-Solanine against Pancreatic Cancer in Vitro and in Vivo. PLOS ONE, 9, e87868. https://doi.org/10.1371/journal.pone.0087868 |
