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Journal of Traditional Chinese Medicine >

2026 , Vol. 46 >Issue 3: 629 - 640

DOI: https://doi.org/10.19852/j.cnki.jtcm.20260304.001

Original Articles

Evaluation of the anti-apoptotic, anti-platelet aggregation, and pro-angiogenic properties of Naoshuantong capsule (脑栓通) in ischemic stroke: insights from network pharmacology and animal experiments

  • LI Chuanpeng ,
  • YAO Yaoyao ,
  • XU Yingzhi ,
  • JIANG Ping ,
  • FENG Luda ,
  • GAO Ying ,
  • DONG Xinglu
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  • 1 Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
    2 Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing 100700, China
    3 Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China
    4 Chinese Medicine Key Research Room of Brain Disorders Syndrome and Treatment of the National Administration of Traditional Chinese Medicine, Beijing 100700, China
Prof. GAO Ying, Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100007, China. gaoying973@163.com;
Dr. DONG Xinglu, Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100007, China. arthasdxl@163.com, Telephone: +86-10-84013258

Received date: 2025-03-07

  Accepted date: 2025-08-18

  Online published: 2026-03-04

Supported by

Research on the Mechanism of Naoshuantong capsule in Treatment of Ischemic Stroke Based on Network Pharmacology(601249);National Natural Science Foundation of China (Young Scientists Fund), “Study on the Effects and Mechanisms of Detoxification and Collateral-Unblocking Therapy on Ischemic Stroke by Regulating Mitochondria-associated ER membranes Ca2+ Homeostasis via the Inositol 1,4,5-trisphosphate Receptor Type 1-Glucose-regulated Protein 75-Voltage-dependent Anion Channel 1 Complex”(82405317);Beijing Municipal level Traditional Chinese Medicine Expert Academic Experience Inheritance Work Project(202279);Research on the Phar macological Mechanism of Naoshuantong Capsule in the Treatment of Ischemic Stroke and Cerebral Small Vessel Disease(601418qt)

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Abstract

OBJECTIVE: To explore the complex molecular mechanisms of Naoshuantong capsule (脑栓通, NST), a Traditional Chinese Medicine formula, against ischemic stroke (IS) using network pharmacology and various experimental verifications.

METHODS: This study employed an integrative approach that combined network pharmacology with experimental validation. Specifically, a network pharmacology model was developed to clarify the fundamental mechanisms and essential NST targets against IS. The core targets and pathways were verified using molecular docking and animal experiments. Additionally, the predicted effects of NST were confirmed by a series of experimental techniques, including hematoxylin-eosin staining, platelet aggregation, flow cytometry, and Western blotting.

RESULTS: A total of 299 targets for overlap of compounds-disease targets were predicted. Protein-protein interaction (PPI) network analysis revealed that the top 30 core targets. Subsequent molecular docking analysis demonstrated that serine-threonine protein kinase 1 (AKT1), phosphoinositide 3-kinase (PI3K), and vascular endothelial growth factor A (VEGFA) have significant binding abilities with these compounds. Gene ontology (GO) enrichment analysis indicated that NST mechanisms against IS involved anti-apoptosis, antiplatelet-aggregation, and angiogenesis ability, confirmed by animal experiments. GO pathway analysis further showed that the mechanism of NST in treating IS was associated PI3K-AKT signaling. Ultimately, this study determined that NST downregulated cleaved-caspase-3 expression while upregulated phosphorylated AKT (P-AKT)/AKT, phosphatidylinositol-4,5-Bisphosphate 3-kinase/PI3K, B-cell lymphoma-2 (Bcl-2)/Bcl-2-associated X protein, and VEGFA expressions.

CONCLUSION: The analysis utilizing multiple approaches manifested that NST has anti-apoptotic, antiplatelet-aggregation, and pro-angiogenic properties in managing IS, offering a systemic outlook for investigating the impact of NST on IS.

Key words： ischemic stroke; network pharmacology; phosphatidylinositol 3-kinase; proto-oncogene proteins c-akt; signal transduction; Naoshuantong capsule

Cite this article

LI Chuanpeng , YAO Yaoyao , XU Yingzhi , JIANG Ping , FENG Luda , GAO Ying , DONG Xinglu . Evaluation of the anti-apoptotic, anti-platelet aggregation, and pro-angiogenic properties of Naoshuantong capsule (脑栓通) in ischemic stroke: insights from network pharmacology and animal experiments[J]. Journal of Traditional Chinese Medicine, 2026 , 46(3) : 629 -640 . DOI: 10.19852/j.cnki.jtcm.20260304.001

References

1. Thayabaranathan T, Kim J, Cadilhac DA, et al. Global stroke statistics 2022. Int J Stroke 2022; 17: 946-56.
2. Sun T, Chen S, Wu K, Sun M, Zhang X, You C. Trends in incidence and mortality of stroke in China from 1990 to 2019. Front Neurol 2021; 12: 759221.
3. Tu W J, Hua Y, Yan F, et al. Prevalence of stroke in China, 2013-2019: a population-based study. Lancet Reg Health West Pac 2022; 28: 100550.
4. Mosconi MG, Paciaroni M. Treatments in ischemic stroke: current and future. Eur Neurol 2022; 85: 349-66.
5. Charbonnier G, Bonnet L, Biondi A, Moulin T. Intracranial bleeding after reperfusion therapy in acute ischemic stroke. Front Neurol 2020; 11: 629920.
6. Nie X, Wang D, Pu Y, et al. Endovascular treatment with or without intravenous alteplase for acute ischaemic stroke due to basilar artery occlusion. Stroke Vasc Neurol 2022; 7: 190-9.
7. Huang CX, Gao Y, Yu Q, Feng LQ. Herbal compound Naoshuantong capsule attenuates retinal injury in ischemia/reperfusion rat model by inhibiting apoptosis. Int J Clin Exp Med 2015; 8: 12252-63.
8. Zhang H, Xing Y, Chang J, et al. Efficacy and safety of Naoshuantong capsule in the treatment of ischemic stroke: a Meta-analysis. Front Pharmacol 2019; 10: 1133.
9. Yang R, Liu C, Li Q, et al. Artificial intelligence based identification of the functional role of hirudin in diabetic erectile dysfunction treatment. Pharmacol Res 2021; 163: 105244.
10. Zhang Y, Mao X, Guo Q, et al. Pathway of ppar-gamma coactivators in thermogenesis: a pivotal Traditional Chinese Medicine-associated target for individualized treatment of rheumatoid arthritis. Oncotarget 2016; 7: 15885-900.
11. Zuo J, Wang X, Liu Y, et al. Integrating network pharmacology and metabolomics study on anti-rheumatic mechanisms and antagonistic effects against methotrexate-induced toxicity of Qing-luo-yin. Front Pharmacol 2018; 9: 1472.
12. Zhao J, Lü C, Wu Q, et al. Computational systems pharmacology reveals an antiplatelet and neuroprotective mechanism of Deng-zhan-xi-xin injection in the treatment of ischemic stroke. Pharmacol Res 2019; 147: 104365.
13. Cui Q, Zhang YL, Ma YH, et al. A network pharmacology approach to investigate the mechanism of Shuxuening injection in the treatment of ischemic stroke. J Ethnopharmacol 2020; 257: 112891.
14. Chinese Pharmacopoeia Commission. Pharmacopoeia of the People's Republic of China. 2020 ed. Beijing: China Medical Science Press, 2020: 1-5576.
15. Rucker V, Heuschmann PU, O'Flaherty M, et al. Twenty-year time trends in long-term case-fatality and recurrence rates after ischemic stroke stratified by etiology. Stroke 2020; 51: 2778-85.
16. Wang Y J, Li Z X, Gu H Q, et al. China stroke statistics: an update on the 2019 report from the national center for healthcare quality management in neurological diseases, China national clinical research center for neurological diseases, the Chinese stroke association, national center for chronic and non-communicable disease control and prevention, Chinese center for disease control and prevention and institute for global neuroscience and stroke collaborations. Stroke Vasc Neurol 2022; 7: 415-50.
17. Duloquin G, Graber M, Baptiste L, et al. Management of ischemic stroke in the acute phase. Rev Med Interne 2022; 43: 286-92.
18. Liu H, Jing J, Wang A, et al. Stroke recurrence and antiplatelets in posterior versus anterior circulation minor stroke or transient ischemic attack. Stroke 2023; 54: 964-72.
19. Zhang W, Wu Y, Chen H, Yu D, Zhao J, Chen J. Neuroprotective effects of sox 5 against ischemic stroke by regulating VEGF/PI3K/AKT pathway. Gene 2021; 767: 145148.
20. Hong M, Shi H, Wang N, Tan HY, Wang Q, Feng Y. Dual effects of chinese herbal medicines on angiogenesis in cancer and ischemic stroke treatments: role of HIF-1 network. Front Pharmacol 2019; 10: 696.
21. Hsu CC, Kuo TW, Liu WP, Chang CP, Lin HJ. Calycosin preserves BDNF/TRKB signaling and reduces post-stroke neurological injury after cerebral ischemia by reducing accumulation of hypertrophic and TNF-alpha-containing microglia in rats. J Neuroimmune Pharmacol 2020; 15: 326-39.
22. Borlongan MC, Kingsbury C, Salazar FE, et al. IL-2/IL-2R antibody complex enhances treg-induced neuroprotection by dampening TNF-alpha inflammation in an in vitro stroke model. Neuromolecular Med 2021; 23: 540-8.
23. Zhang W, Ren CH, Gao C, Xu J, Wu XD, Yang Y. Systematic understanding of mechanism of Shenfu decoction improve the prognosis of ischemic stroke using a network pharmacology and animal experiment approach. J Tradit Chin Med 2025; 45: 1078-86.
24. Wu MY, Yiang GT, Liao WT, et al. Current mechanistic concepts in ischemia and reperfusion injury. Cell Physiol Biochem 2018; 46: 1650-67.
25. Khoshnam SE, Winlow W, Farzaneh M, Farbood Y, Moghaddam HF. Pathogenic mechanisms following ischemic stroke. Neurol Sci 2017; 38: 1167-86.
26. Uzdensky AB. Apoptosis regulation in the penumbra after ischemic stroke: expression of pro- and antiapoptotic proteins. Apoptosis 2019; 24: 687-702.
27. Cui Y, Liu M, Zuo L, Wang H, Liu J. Fraxetin protects rat brains from the cerebral stroke via promoting angiogenesis and activating PI3K/AKT pathway. Immunopharmacol Immunotoxicol 2022; 44: 400-9.
28. Zheng T, Jiang TT, Ma HX, Zhu YP, Wang MX. Targeting PI3K/AKT in cerebral ischemia reperfusion injury alleviation: from signaling networks to targeted therapy. Mol Neurobiol 2024; 61: 7930-49.
29. Kilic U, Caglayan AB, Beker MC, et al. Particular phosphorylation of PI3K/AKT on THr308 via PDK-1 and PTEN mediates melatonin's neuroprotective activity after focal cerebral ischemia in mice. Redox Biol 2017; 12: 657-65.
30. Zhao GC, Yuan YL, Chai FR, Ji FJ. Effect of melilotus officinalis extract on the apoptosis of brain tissues by altering cerebral thrombosis and inflammatory mediators in acute cerebral ischemia. Biomed Pharmacother 2017; 89: 1346-52.
31. Liu JF, Su G, Chen LX, et al. Irisin attenuates apoptosis following ischemia-reperfusion injury through improved mitochondria dynamics and ROS suppression mediated through the PI3K/Akt/mTOR axis. Mol Neurobiol 2023; 60: 4261-72.
32. Yang Y, Zhang XJ, Li LT, et al. Apelin-13 protects against apoptosis by activating amp-activated protein kinase pathway in ischemia stroke. Peptides 2016; 75: 96-100.
33. Hovhannesyan RA, Hovhannisyan IG. Platelet aggregation and interleukins indicators impacting the outcomes of ischemic stroke. J Stroke Cerebrovasc Dis 2019; 28: 2038-44.
34. Stegner D, Klaus V, Nieswandt B. Platelets as modulators of cerebral ischemia/reperfusion injury. Front Immunol 2019; 10: 2505.
35. Koo YK, Kim JM, Koo JY, et al. Platelet anti-aggregatory and blood anti-coagulant effects of compounds isolated from paeonia lactiflora and paeonia suffruticosa. Pharmazie 2010; 65: 624-8.
36. Deng L, Zhang F, Wu Y, et al. RGD-modified nanocarrier-mediated targeted delivery of HIF-1α-AA plasmid DNA to cerebrovascular endothelial cells for ischemic stroke treatment. ACS Biomater Sci Eng 2019; 5: 6254-64.
37. Huang W, Shao M, Liu H, et al. Fibroblast growth factor 21 enhances angiogenesis and wound healing of human brain microvascular endothelial cells by activating ppargamma. J Pharmacol Sci 2019; 140: 120-7.
38. Hatakeyama M, Ninomiya I, Kanazawa M. Angiogenesis and neuronal remodeling after ischemic stroke. Neural Regen Res 2020; 15: 16-9.
39. Luo S, Yang F, Chen YC, et al. Sanhua Tang (三化汤) protects against ischemic stroke by preventing blood-brain barrier injury: a network pharmacology and in vivo experiments. J Tradit Chin Med 2024; 44: 794-803.
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