Skip to content
2000
Volume 21, Issue 6
  • ISSN: 1573-4099
  • E-ISSN: 1875-6697

Abstract

Background

Shenfu injection was derived from the classical Chinese medicine formula ‘Shenfu decoction’, which was widely used in the treatment of cardiovascular and cerebrovascular diseases in clinical practice.

Objectives

Predict the main active ingredients, core targets, and related signaling pathways of Shenfu injection in the treatment of ischemic stroke.

Methods

Databases were used to collect the active ingredients and target information of Shenfu injection; GO and KEGG pathway enrichment analyses were performed using the David database. The effects of Shenfu injection on core targets were verified using molecular docking and experiments.

Results

The predicted results identified 44 active ingredients and 635 targets in Shenfu injection, among which 418 targets, including TNF, IL-6, MAPK1, and MAPK14, were potential targets for the treatment of ischemic stroke. Molecular docking revealed that the active ingredients had good binding to IL-6, MAPK1, and MAPK14. experiments demonstrated that Shenfu injection significantly improved the pathological damage due to ischemic stroke, promoted the expression of tight junction proteins, and inhibited MMP-2 and MMP-9 expressions, thereby reducing BBB permeability. Animal experiments revealed that Shenfu injection could inhibit p38、JNK and ERK phosphorylation.

Conclusion

Mechanism of Shenfu injection in treating ischemic stroke may be inhibition of the inflammatory factors levels and protecting the BBB, thereby warranting subsequent studies and highlighting its potential as a reference for new drug development.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cad/10.2174/0115734099292513240404091734
2024-04-15
2025-12-06

  • From This Site

    /content/journals/cad/10.2174/0115734099292513240404091734
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. TaterP. PandeyS. Post-stroke movement disorders: Clinical spectrum, pathogenesis, and management.Neurol. India202169227228310.4103/0028‑3886.314574 33904435
     [Google Scholar]
  2. ZhaoY. ZhangX. ChenX. WeiY. Neuronal injuries in cerebral infarction and ischemic stroke: From mechanisms to treatment (Review).Int. J. Mol. Med.20224921510.3892/ijmm.2021.5070 34878154
     [Google Scholar]
  3. CampbellB.C.V. De SilvaD.A. MacleodM.R. CouttsS.B. SchwammL.H. DavisS.M. DonnanG.A. Ischaemic stroke.Nat. Rev. Dis. Primers2019517010.1038/s41572‑019‑0118‑8 31601801
     [Google Scholar]
  4. PohlM. HesszenbergerD. KapusK. MeszarosJ. FeherA. VaradiI. PuschG. FejesE. TiboldA. FeherG. Ischemic stroke mimics: A comprehensive review.J. Clin. Neurosci.20219317418210.1016/j.jocn.2021.09.025 34656244
     [Google Scholar]
  5. MaidaC.D. NorritoR.L. DaidoneM. TuttolomondoA. PintoA. Neuroinflammatory mechanisms in ischemic stroke: focus on cardioembolic stroke, background, and therapeutic approaches.Int. J. Mol. Sci.20202118645410.3390/ijms21186454 32899616
     [Google Scholar]
  6. YangY. ZhangM. ZhaoJ. SongS. HongF. ZhangG. Effect of traditional Chinese medicine emotional therapy on poststroke depression: A protocol for systematic review and meta-analysis.Medicine (Baltimore)202110014e2538610.1097/MD.000000000002538633832127
     [Google Scholar]
  7. ChavezL. HuangS.S. MacDonaldI. LinJ.G. LeeY.C. ChenY.H. Mechanisms of acupuncture therapy in ischemic stroke rehabilitation: A literature review of basic studies.Int. J. Mol. Sci.20171811227010.3390/ijms18112270 29143805
     [Google Scholar]
  8. DongR. HuangR. ShiX. XuZ. MangJ. Exploration of the mechanism of luteolin against ischemic stroke based on network pharmacology, molecular docking and experimental verification.Bioengineered2021122122741229310.1080/21655979.2021.2006966 34898370
     [Google Scholar]
  9. LinS. ShiQ. GeZ. LiuY. CaoY. YangY. ZhaoZ. BiY. HouY. WangS. WangX. MaoJ. Efficacy and safety of traditional chinese medicine injections for heart failure with reduced ejection fraction: a bayesian network meta-analysis of randomized controlled trials.Front. Pharmacol.20211265970710.3389/fphar.2021.659707 34916929
     [Google Scholar]
  10. LiP. LvB. JiangX. WangT. MaX. ChangN. WangX. GaoX. Identification of nf-κb inhibitors following shenfu injection and bioactivity-integrated uplc/q-tof-ms and screening for related anti-inflammatory targets in vitro and in silico.J. Ethnopharmacol.201619465866710.1016/j.jep.2016.10.052 27771457
     [Google Scholar]
  11. GuoB. YangT. NanJ. HuangQ. WangC. XuW. Efficacy and safety of Shenfu injection combined with sodium nitroprusside in the treatment of chronic heart failure in patients with coronary heart disease. A protocol of randomized controlled trial.Medicine20211007e2441410.1097/MD.0000000000024414 33607775
     [Google Scholar]
  12. WangY. LiY. LiL. YangD. ZhouK. LiY. Protective effects of shenfu injection against myocardial ischemia–reperfusion injury via activation of enos in rats.Biol. Pharm. Bull.20184191406141310.1248/bpb.b18‑00212 29910216
     [Google Scholar]
  13. ShiK. XiaoY. DongY. WangD. XieY. TuJ. XuK. ZhouZ. CaoG. LiuY. Protective Effects of Atractylodis lancea Rhizoma on Lipopolysaccharide-Induced Acute Lung Injury via TLR4/NF-κB and Keap1/Nrf2 Signaling Pathways In Vitro and In Vivo.Int. J. Mol. Sci.202223241613410.3390/ijms232416134 36555773
     [Google Scholar]
  14. KimY. LeeS. ZhangH. LeeS. KimH. KimY. WonM.H. KimY.M. KwonY.G. CLEC14A deficiency exacerbates neuronal loss by increasing blood-brain barrier permeability and inflammation.J. Neuroinflammation20201714810.1186/s12974‑020‑1727‑6 32019570
     [Google Scholar]
  15. AbdullahiW. TripathiD. RonaldsonP.T. Blood-brain barrier dysfunction in ischemic stroke: targeting tight junctions and transporters for vascular protection.Am. J. Physiol. Cell Physiol.20183153C343C35610.1152/ajpcell.00095.2018 29949404
     [Google Scholar]
  16. ZhangS. AnQ. WangT. GaoS. ZhouG. Autophagy- and MMP-2/9-mediated Reduction and Redistribution of ZO-1 Contribute to Hyperglycemia-increased Blood–Brain Barrier Permeability During Early Reperfusion in Stroke.Neuroscience201837712613710.1016/j.neuroscience.2018.02.035 29524637
     [Google Scholar]
  17. HannocksM.J. ZhangX. GerwienH. ChashchinaA. BurmeisterM. KorposE. SongJ. SorokinL. The gelatinases, MMP-2 and MMP-9, as fine tuners of neuroinflammatory processes.Matrix Biol.201975-7610211310.1016/j.matbio.2017.11.007 29158162
     [Google Scholar]
  18. CaoZ.Q. YuX. LengP. Research progress on the role of gal-3 in cardio/cerebrovascular diseases.Biomed. Pharmacother.202113311106610.1016/j.biopha.2020.111066 33378967
     [Google Scholar]
  19. LuJ. LiuW. ZhaoH. Headache in cerebrovascular diseases.Stroke Vasc. Neurol.20205220521010.1136/svn‑2020‑000333 32606088
     [Google Scholar]
  20. WestendorpW.F. DamesC. NederkoornP.J. MeiselA. Immunodepression, infections, and functional outcome in ischemic stroke.Stroke20225351438144810.1161/STROKEAHA.122.038867 35341322
     [Google Scholar]
  21. MarkV.W. Stroke and Behavior.Neurol. Clin.201634120523410.1016/j.ncl.2015.08.009 26614000
     [Google Scholar]
  22. CaprioF.Z. SorondF.A. Cerebrovascular Disease.Med. Clin. North Am.2019103229530810.1016/j.mcna.2018.10.001 30704682
     [Google Scholar]
  23. KalariaR.N. AkinyemiR. IharaM. Stroke injury, cognitive impairment and vascular dementia.Biochim. Biophys. Acta Mol. Basis Dis.20161862591592510.1016/j.bbadis.2016.01.015 26806700
     [Google Scholar]
  24. WuS. WuB. LiuM. ChenZ. WangW. AndersonC.S. SandercockP. WangY. HuangY. CuiL. PuC. JiaJ. ZhangT. LiuX. ZhangS. XieP. FanD. JiX. WongK.S.L. WangL. WuS. WuB. LiuM. ChenZ. WangW. AndersonC.S. SandercockP. WangY. HuangY. CuiL. PuC. JiaJ. ZhangT. LiuX. ZhangS. XieP. FanD. JiX. WongK-S.L. WangL. WeiC. WangY. ChengY. LiuY. LiX. DongQ. ZengJ. PengB. XuY. YangY. WangY. ZhaoG. WangW. XuY. YangQ. HeZ. WangS. YouC. GaoY. ZhouD. HeL. LiZ. YangJ. LeiC. ZhaoY. LiuJ. ZhangS. TaoW. HaoZ. WangD. ZhangS. Stroke in China: advances and challenges in epidemiology, prevention, and management.Lancet Neurol.201918439440510.1016/S1474‑4422(18)30500‑3 30878104
     [Google Scholar]
  25. DengH. TangZ. TuoP. WuR. JiaS. ZhaoX. HuangD. GaoY. LanZ. Shenfu injection protects brain injury in rats with cardiac arrest through nogo/ngr pathway.Anal. Cell. Pathol.202220221810.1155/2022/4588999 36600931
     [Google Scholar]
  26. GuoZ.J. LiC.S. Therapeutic effects of Shenfu Injection on post-cardiac arrest syndrome.Chin. J. Integr. Med.201319971672010.1007/s11655‑013‑1566‑8 23975138
     [Google Scholar]
  27. QinC. YangS. ChuY.H. ZhangH. PangX.W. ChenL. ZhouL.Q. ChenM. TianD.S. WangW. Signaling pathways involved in ischemic stroke: molecular mechanisms and therapeutic interventions.Signal Transduct. Target. Ther.20227121510.1038/s41392‑022‑01064‑1 35794095
     [Google Scholar]
  28. RegenhardtR.W. DasA.S. LoE.H. CaplanL.R. Advances in understanding the pathophysiology of lacunar stroke.JAMA Neurol.201875101273128110.1001/jamaneurol.2018.1073 30167649
     [Google Scholar]
  29. ZhouZ. LuJ. LiuW.W. ManaenkoA. HouX. MeiQ. HuangJ.L. TangJ. ZhangJ.H. YaoH. HuQ. Advances in stroke pharmacology.Pharmacol. Ther.2018191234210.1016/j.pharmthera.2018.05.012 29807056
     [Google Scholar]
  30. ZhuH. HuS. LiY. SunY. XiongX. HuX. ChenJ. QiuS. Interleukins and Ischemic Stroke.Front. Immunol.20221382844710.3389/fimmu.2022.828447 35173738
     [Google Scholar]
  31. Candelario-JalilE. DijkhuizenR.M. MagnusT. Neuroinflammation, stroke, blood-brain barrier dysfunction, and imaging modalities.Stroke20225351473148610.1161/STROKEAHA.122.036946 35387495
     [Google Scholar]
  32. PanJ. QuM. LiY. WangL. ZhangL. WangY. TangY. TianH.L. ZhangZ. YangG.Y. MicroRNA-126-3p/-5p overexpression attenuates blood-brain barrier disruption in a mouse model of middle cerebral artery occlusion.Stroke202051261962710.1161/STROKEAHA.119.027531 31822249
     [Google Scholar]
  33. PanL. PengC. WangL. LiL. HuangS. FeiC. WangN. ChuF. PengD. DuanX. Network pharmacology and experimental validation-based approach to understand the effect and mechanism of Taohong Siwu Decoction against ischemic stroke.J. Ethnopharmacol.202229411533910.1016/j.jep.2022.115339 35525530
     [Google Scholar]
  34. WangH. RanH. YinY. XuX. JiangB. YuS. ChenY. RenH. FengS. ZhangJ. ChenY. XueQ. XuX. Catalpol improves impaired neurovascular unit in ischemic stroke rats via enhancing VEGF-PI3K/AKT and VEGF-MEK1/2/ERK1/2 signaling.Acta Pharmacol. Sin.20224371670168510.1038/s41401‑021‑00803‑4 34795412
     [Google Scholar]
/content/journals/cad/10.2174/0115734099292513240404091734
Loading
Mechanism of Shenfu Injection in Treating Ischemic Stroke Elucidated using Network Pharmacology and Experimental Validation
Curr. Computeraided Drug Des. 21, 793 (2025); https://doi.org/10.2174/0115734099292513240404091734
/content/journals/cad/10.2174/0115734099292513240404091734
/content/journals/cad/10.2174/0115734099292513240404091734
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): ischemic stroke; KEGG pathway; MAPK pathway; network pharmacology; Shenfu injection; tight junction

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test