Innovation Series: Advanced Science (ISSN 2938-9933, CNKI Indexed)

Volume 2 · Issue 6 (2025)
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Investigating Zhishi's Therapeutic Mechanism in Stroke Management via Network Pharmacology

 

Fang He

Department of Rehabilitation Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, China

 

Abstract: Purpose: To investigate the mediation process of Zhishi in stroke using network pharmacology methodologies. Methods: To pinpoint the key components and potential focus areas of Zhishi, the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and analysis tools were put to work. Targets relevant to strokes were identified across several gene-related databases, including GeneCards, OMIM, DrugBank, and TTD. By utilizing an online Venny analysis tool, common targets between Zhishi and stroke conditions were uncovered. A network depicting these shared Zhishi-stroke targets was then mapped out with Cytoscape software. A protein-protein interaction (PPI) network was crafted using the STRING database, which was followed by a detailed topological analysis of the shared targets to pinpoint crucial ones. With RStudio, the most relevant top 10 GO terms and the top 30 KEGG pathways for these shared targets were meticulously selected and visualized for a comprehensive enrichment analysis. Result: An analysis of the Zhishi database revealed 17 active components and 111 associated targets. Notably, 78 of these targets have been linked to stroke. The herb’s primary active components are luteolin, naringenin, and nobiletin. The study underscored key targets like TNF, AKT1, and BCL2. The gene ontology enrichment indicates involvement in biological processes such as response to UV, response to xenobiotic stimulus, and response to light stimulus. Furthermore, KEGG pathway enrichment hints at how Zhishi might intervene in strokes, potentially through roles in Lipid and atherosclerosis, Prostate cancer signaling pathway, Toxoplasmosis, and Hepatitis B. Conclusion: Zhishi demonstrates therapeutic potential for stroke via its various components impacting multiple targets.

 

Keywords: Network Pharmacology; Stroke, Mechanism; Zhishi

 

References

[1]
Jickling, G.C., et al., Hemorrhagic transformation after ischemic stroke in animals and humans. J Cereb Blood Flow Metab, 2014. 34(2): p. 185-99.
[2]
Otero-Ortega, L., et al., Role of Exosomes as a Treatment and Potential Biomarker for Stroke. Transl Stroke Res, 2019. 10(3): p. 241-249.
[3]
Chen, H., et al., Therapeutic targets of oxidative/nitrosative stress and neuroinflammation in ischemic stroke: Applications for natural product efficacy with omics and systemic biology. Pharmacol Res, 2020. 158: p. 104877.
[4]
Zhang, P., et al., Network pharmacology: towards the artificial intelligence-based precision traditional Chinese medicine. Brief Bioinform, 2023. 25(1).
[5]
Zhai, Z., et al., Progress on traditional Chinese medicine in treatment of ischemic stroke via the gut-brain axis. Biomed Pharmacother, 2023. 157: p. 114056.
[6]
L, L.Y., H.Z. Y, and T.R. Q, Effect of Zhishi on IL-6, SCF and MTL in rats with functional dyspepsia. Shanxi J Tradit Chin Med. 36(1): p. 52-53, 62.
[7]
Global, regional, and national burden of stroke and its risk factors, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet Neurol, 2024. 23(10): p. 973-1003.
[8]
Global burden of 292 causes of death in 204 countries and territories and 660 subnational locations, 1990-2023: a systematic analysis for the Global Burden of Disease Study 2023. Lancet, 2025. 406(10513): p. 1811-1872.
[9]
Sun, H., et al., Incidence of First-Ever Stroke, Stroke Events, and Early Case Fatality Rate in China: Results from a National Population-Based Survey. Neuroepidemiology, 2025. 59(6): p. 714-726.
[10]
Sacco, R.L., et al., An updated definition of stroke for the 21st century: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke, 2013. 44(7): p. 2064-89.
[11]
Maida, C.D., et al., Molecular Pathogenesis of Ischemic and Hemorrhagic Strokes: Background and Therapeutic Approaches. Int J Mol Sci, 2024. 25(12).
[12]
Tsivgoulis, G., et al., Thrombolysis for acute ischaemic stroke: current status and future perspectives. Lancet Neurol, 2023. 22(5): p. 418-429.
[13]
Zhang, H., et al., Pharmacodynamic advantages and characteristics of traditional Chinese medicine in prevention and treatment of ischemic stroke. Chin Herb Med, 2023. 15(4): p. 496-508.
[14]
Correction to: An Updated Definition of Stroke for the 21st Century: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke, 2019. 50(8): p. e239.
[15]
Iadecola, C. and J. Anrather, The immunology of stroke: from mechanisms to translation. Nat Med, 2011. 17(7): p. 796-808.
[16]
Kim, S., U.J. Jung, and S.R. Kim, The Crucial Role of the Blood-Brain Barrier in Neurodegenerative Diseases: Mechanisms of Disruption and Therapeutic Implications. J Clin Med, 2025. 14(2).
[17]
Fu, J., et al., Naringenin promotes angiogenesis of ischemic myocardium after myocardial infarction through miR-223-3p/IGF1R axis. Regen Ther, 2022. 21: p. 362-371.
[18]
Wang, M., et al., Microglia-Mediated Neuroinflammation: A Potential Target for the Treatment of Cardiovascular Diseases. J Inflamm Res, 2022. 15: p. 3083-3094.
[19]
Zhang, L., et al., Nobiletin promotes antioxidant and anti-inflammatory responses and elicits protection against ischemic stroke in vivo. Brain Res, 2016. 1636: p. 130-141.
[20]
Zhao, M., et al., Multi-Target and Multi-Phase Adjunctive Cerebral Protection for Acute Ischemic Stroke in the Reperfusion Era. Biomolecules, 2024. 14(9).
[21]
Gao, T., et al., Melatonin-mediated MT2 attenuates colitis induced by dextran sodium sulfate via PI3K/AKT/Nrf2/SIRT1/RORα/NF-κB signaling pathways. Int Immunopharmacol, 2021. 96: p. 107779.
[22]
Li, S., et al., An effective solution to discover synergistic drugs for anti-cerebral ischemia from traditional Chinese medicinal formulae. PLoS One, 2013. 8(11): p. e78902.
[23]
Chen, A.Q., et al., Microglia-derived TNF-α mediates endothelial necroptosis aggravating blood brain-barrier disruption after ischemic stroke. Cell Death Dis, 2019. 10(7): p. 487.
[24]
Vaux, D.L., S. Cory, and J.M. Adams, Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature, 1988. 335(6189): p. 440-2.
[25]
DeVries, A.C., et al., Social stress exacerbates stroke outcome by suppressing Bcl-2 expression. Proc Natl Acad Sci U S A, 2001. 98(20): p. 11824-8.
[26]
Schäbitz, W.R., et al., Intravenous brain-derived neurotrophic factor reduces infarct size and counter regulates Bax and Bcl-2 expression after temporary focal cerebral ischemia. Stroke, 2000. 31(9): p. 2212-7.
[27]
Staal, S.P., Molecular cloning of the akt oncogene and its human homologues AKT1 and AKT2: amplification of AKT1 in a primary human gastric adenocarcinoma. Proc Natl Acad Sci U S A, 1987. 84(14): p. 5034-7.
[28]
Wang, C., et al., Human-induced pluripotent stem cell-derived neural stem cell exosomes improve blood-brain barrier function after intracerebral hemorrhage by activating astrocytes via PI3K/AKT/MCP-1 axis. Neural Regen Res, 2025. 20(2): p. 518-532.
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