Objective  To explore the multi-target and multi-pathway mechanisms of Codonopsis pilosula (Dangshen) in the treatment of myocardial injury, and to verify the interactions between its main active components and key target proteins using molecular docking.

Methods   Network pharmacology was applied to systematically retrieve and screen the potential active compounds of Codonopsis pilosula and the targets related to myocardial injury from public databases. The intersection targets were identified to construct a protein-protein interaction (PPI) network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were then performed to elucidate the biological processes and signaling pathways involved. The core active compounds and key proteins were further analyzed by molecular docking to evaluate binding energies, validate potential binding modes, and predict underlying mechanisms.

Results  A total of 350 overlapping targets between Codonopsis pilosula and myocardial injury were identified. PPI network analysis indicated that proteins such as interleukin-6 (IL-6), RAC-alpha serine/threonine-protein kinase (AKT1), interleukin-1β (IL-1β), insulin (INS), tumor protein p53 (TP53), tumor necrosis factor-alpha (TNF-α), and albumin (ALB) exhibited high centrality. GO and KEGG enrichment analyses revealed that these targets were significantly enriched in key biological processes, including inflammation, apoptosis, metabolic homeostasis, and hypoxia response. Molecular docking further demonstrated that the core compounds, frutinone A and 7-methoxy-2-methyl isoflavone, could stably bind to these key proteins, suggesting that Codonopsis pilosula exerts cardioprotective effects through multiple signaling pathways in a synergistic manner.

Conclusion   Based on network pharmacology and molecular docking, Codonopsis pilosula may alleviate myocardial injury by regulating key signaling proteins such as AKT1, TNF, and IL-6, and by participating in signaling pathways including phosphoinositide 3-kinase (PI3K)-AKT, TNF, and HIF-1. These findings highlight the multi-target characteristics of Codonopsis pilosula and provide a reference for its cardioprotective mechanisms.

1.Lu L, Liu M, Sun R, et al. Myocardial infarction: symptoms and treatments[J]. Cell Biochem Biophys, 2015, 72(3): 865-867. DOI: 10.1007/s12013-015-0553-4.

2.Murray CJL, Lopez AD. Global mortality, disability, and the contribution of risk factors: global burden of disease study[J]. Lancet, 1997, 349(9063): 1436-1442. DOI: 10.1016/S0140-6736(96)07495-8.

3.GBD 2019 Diseases and Injuries Collaborators. Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019[J]. Lancet, 2020, 396(10258): 1204-1222. DOI: 10.1016/S0140-6736(20)30925-9.

4.Benjamin EJ, Muntner P, Alonso A, et al. Heart disease and stroke statistics—2019 update: a report from the american heart association[J]. Circulation, 2019, 139(10): e56-e528. DOI: 10.1161/CIR.0000000000000659.

5.Roth GA, Johnson C, Abajobir A, et al. Global, regional, and national burden of cardiovascular diseases for 10 causes, 1990 to 2015[J]. J Am Coll Cardiol, 2017, 70(1): 1-25. DOI: 10.1016/j.jacc.2017.04.052.

6.Spatz ES, Wang Y, Beckman AL, et al. Traditional Chinese medicine for acute myocardial infarction in western medicine hospitals in China[J]. Circ Cardiovasc Qual Outcomes, 2018, 11(3): e004190. DOI: 10.1161/CIRCOUTCOMES.117.004190.

7.张重阳, 于淼, 陈荣昌, 等. 党参药理作用的研究进展 [J]. 中药新药与临床药理, 2024, 35(5): 765-770. [Zeng RY, Yu M, Chen RC, et al. Research progress on pharmacological effects of Codonopsis Radix[J]. Chinese Journal of New Drugs and Clinical Remedies, 2024, 35(5): 765-770.] DOI: 10.19378/j.issn.1003-9783.2024.05.019.

8.张欢, 李超, 汲晨锋. 药食同源党参化学成分、药理作用及应用研究进展[J]. 食品科学, 2024, 45(23): 338-348. [Zhang H, Li C, Ji C. Research progress on chemical constituents, pharmacological activities and applications of Codonopsis Radix as both medicine and food[J]. Food Science, 2024, 45(23): 338-348.] DOI: 10.7506/spkx1002-6630-20240524-201.

9.李富云, 南丽丽, 杨锡仓, 等. 党参化学成分、药理作用及质量控制研究进展[J]. 甘肃中医药大学学报, 2024, 41(5): 79-83. [Li FY, Nan LL, Yang XC, et al. Research progress on the chemical composition,pharmacological effects and quality control of Codonopsis pilosula[J]. Journal of Gansu University of Traditional Chinese Medicine, 2024, 41(5): 79-83.] DOI: 10.16841/j.issn1003-8450.2024.05.13.

10.向施, 张文文, 陈慧, 等. 党参炔苷药理作用机制研究进展 [J]. 辽宁中医药大学学报, 2024, 26(10): 169-173. [Xiang S, Zhang WW, Chen H, et al. Research progress on pharmacological mechanism of lobetyolin[J]. Journal of Liaoning University of Traditional Chinese Medicine, 2024, 26(10): 169-173.] DOI: 10.13194/j.issn.1673-842x.2024.10.034.

11.Hopkins AL. Network pharmacology: the next paradigm in drug discovery[J]. Nat Chem Biol, 2008, 4(11): 682-690. DOI: 10.1038/nchembio.118.

12.Li S, Zhang B. Traditional Chinese medicine network pharmacology: theory, methodology and application[J]. Chin J Nat Med, 2013, 11(2): 110-120. DOI: 10.1016/S1875-5364(13)60037-0.

13.王露露, 李冰, 王圳伊, 等. 基于“整体观”系统生物学技术在中药研究中的应用进展[J]. 中草药, 2020, 51(19): 5053-5064. [Wang LL, Li B, Wang ZY, et al. Application of systematic biology technology in research of traditional Chinese medicine based on overall research[J]. Chinese Traditional and Herbal Drugs, 2020, 51(19): 5053-5064.] DOI: 10.7501/j.issn.0253-2670.2020.19.025.

14.刘美霞, 戚进, 余伯阳. 党参药理作用研究进展[J]. 海峡药学, 2018, 30(11): 36-39. [Liu MX, Qi J, Yu BY. Research progress on the pharmacological activity of Codonopsis pilosula[J]. Strait Pharmaceutical Journal, 2018, 30(11): 36-39.] DOI: 10.3969/j.issn.1006-3765.2018.11.012.

15.Wang Y, Fan X, Qu H, et al. Strategies and techniques for multi-component drug design from medicinal herbs and traditional Chinese medicine[J]. Curr Top Med Chem, 2012, 12(12): 1353-1362. DOI: 10.2174/156802612802816924.

16.Meng XY, Zhang HX, Mezei M, et al. Molecular docking: a powerful approach for structure-based drug discovery[J]. Curr Comput Aided Drug Des, 2011,7(2): 146-157. DOI: 10.2174/157340911795677602.

17.Pagadala NS, Syed K, Tuszynski J. Software for molecular docking: a review[J]. Biophys Rev, 2017, 9(2): 91-102. DOI: 10.1007/s12551-017-0257-1.

18.Dos Santos Nascimento IJ, de Moura RO. Molecular dynamics simulations in drug discovery[J]. Mini Rev Med Chem, 2024, 24(11): 1061-1062. DOI: 10.2174/1389557524999240312091248.

19.Liu C, Huang Y. Chinese herbal medicine on cardiovascular diseases and the mechanisms of action[J]. Front Pharmacol, 2016, 7: 469. DOI: 10.3389/fphar.2016.00469.

20.Fu Y, Wang Y, Zhang B. Systems pharmacology for traditional Chinese medicine with application to cardio-cerebrovascular diseases[J]. J Tradit Chin Med Sci, 2014, 1(2): 84-91. DOI: 10.1016/S2095-4964(14)60018-0.

21.Zhao S, Iyengar R. Systems pharmacology: network analysis to identify multiscale mechanisms of drug action[J]. Annu Rev Pharmacol Toxicol, 2012, 52: 505-521. DOI: 10.1146/annurev-pharmtox-010611-134520.

22.Luo TT, Lu Y, Yan SK, et al. Network pharmacology in research of Chinese medicine formula: methodology, application and prospective[J]. Chin J Integr Med, 2020, 26(1): 72-80. DOI: 10.1007/s11655-019-3194-9.

23.Yildirim MA, Goh KI, Cusick ME, et al. Drug-target network[J]. Nat Biotechnol, 2007, 25(10): 1119-1126. DOI: 10.1038/nbt1338.

24.邢炎华, 张建, 黄壮壮, 等. 基于网络药理学和分子对接的补气通络颗粒抗心血管疾病作用机理研究 [J]. 中国现代医药杂志, 2024, 26(1): 11-16. [Xing YH, Zhang J, Huang ZZ, et al. Mechanism study of Buqi Tongluo granules against cardiovascular diseases based on network pharmacology and molecular docking[J]. China Modern Medicine, 2024, 26(1): 11-16.] DOI: 10.3969/j.issn.1672-9463.2024.01.003.

25.Bavishi C, Bonow RO, Trivedi V, et al. Acute myocardial injury in patients hospitalized with COVID-19 infection: a review[J]. Prog Cardiovasc Dis, 2020, 63(5): 682-689. DOI: 10.1016/j.pcad.2020.04.008.

26.Zhang W, Liu HT. MAPK signal pathways in the regulation of cell proliferation in mammalian cells[J]. Cell Res, 2002, 12(1): 9-18. DOI: 10.1038/sj.cr.7290105.

27.Azzazy HM, Christenson RH. All about albumin: biochemistry, genetics, and medical applications (book review)[J]. Clin Chem, 1997, 43(10): 2014a-2015. DOI: 10.1093/clinchem/43.10.2014a.

28.Sun Z, Wang Y, Pang X, et al. Mechanisms of polydatin against spinal cord ischemia-reperfusion injury based on network pharmacology, molecular docking and molecular dynamics simulation[J]. Bioorg Chem, 2023, 140: 106840. DOI: 10.1016/j.bioorg.2023.106840.

29.Koes DR, Baumgartner MP, Camacho CJ. Lessons learned in empirical scoring with Smina from the CSAR 2011 benchmarking exercise[J]. J Chem Inf Model, 2013, 53(8): 1893-1904. DOI: 10.1021/ci400106m.

30.黄云龙. 植物黄酮类化合物研究进展[J]. 中国果菜, 2025, 45(1): 71-79. [Huang YL. Advances in research on flavonoid compounds in plants[J]. China Fruits & Vegetables, 2025, 45(1): 71-79.] DOI: 10.19590/j.cnki.1008-1038.2025.01.012.

31.Wang S, Cao M, Xu S, et al. Luteolin alters macrophage polarization to inhibit inflammation[J]. Inflammation, 2020, 43: 95-108. DOI: 10.1007/s10753-019-01146-2.

32.Chacko BK, Chandler RT, Mundhekar A, et al. Revealing anti-inflammatory mechanisms of soy isoflavones by flow: modulation of leukocyte-endothelial cell interactions[J]. Am J Physiol Heart Circ Physiol, 2005, 289(2): H908-H915. DOI: 10.1152/ajpheart.00764.2004.

33.王永华, 杨凌. 基于系统药理学的现代中药研究体系 [J]. 世界中医药, 2013, 8(7): 801-808. [Wang YH, Yang L. Systems pharmacology based research framework of traditional Chinese medicine[J]. World Chinese Medicine, 2013, 8(7): 801-808.] DOI: 10.3969/j.issn.1673-7202.2013.07.032.

34.Bryce RA. Physics-based scoring of protein-ligand interactions: explicit polarizability, quantum mechanics and free energies[J]. Future Med Chem, 2011, 3(6): 683-698. DOI: 10.4155/fmc.11.30.