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Abstract

Objective

The objective of this study was to investigate the mechanism of anti-cerebral ischemia-reperfusion injury (anti-CIRI) of Ai pian by using the network pharmacology approach combined with serum metabolomics technique based on UPLC-MS.

Methods

The cerebral ischemia-reperfusion injury (CIRI) model was established by middle cerebral artery occlusion (MCAO). The therapeutic effect of Ai pian on CIRI rats was evaluated by behavioral test, 2,3,5-triphenyltetrazolium chloride (TTC) staining, Nissl staining, and hematoxylin-eosin (HE) staining. The active compound–potential target–disease network for Ai Pian in the treatment of CIRI was established using network pharmacology methods. Rat serum was detected by the metabolomics technique based on UPLC-MS. A Western blot was used to validate common targets of the network pharmacology approach combined with serum metabolomics.

Results

The process of treating CIRI with Ai Pian involved regulating enzyme, nuclear receptor, and transcription factor activity, managing the inflammatory response, and participating in biofilm composition. Twenty endogenous potential biomarkers were screened and submitted to MetaboAnalyst 6.0 for pathway and enrichment analysis. Four metabolic pathways were identified: butanoate metabolism, fructose and mannose metabolism, alanine, aspartate, and glutamate metabolism, and pyrimidine metabolism. Fructose and mannose metabolism and pyrimidine metabolism were two key pathways. Western blot analysis suggested that DHODH, TYMS, and AKR1B1 may be targets through which therapeutic effects are exerted.

Discussion

The present study made preliminary predictions on the possible mechanisms of Ai Pian against CIRI. Differential metabolites were screened and identified, and the relevant metabolic pathways potentially affected by Ai Pian were discovered to understand the importance of these markers in health and disease. However, there were also some limitations, further exploration of the molecular mechanisms at the transcriptional level was necessary to make the experimental results more reliable.

Conclusion

This research contributed to the development of Ai pian as an adjunctive drug for treating CIRI and provided a basis for further research on CIRI.

© 2025 The Author(s). Published by Bentham Science Publishers.
This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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2025-10-31
2025-12-14

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References

  1. Wang Y. Wu Y. Liang C. Tan R. Tan L. Tan R. Pharmacodynamic effect of Ellagic acid on ameliorating Cerebral Ischemia/Reperfusion injury. Pharmacology 2019 104 5-6 320 331 10.1159/000502401 31473749
    [Google Scholar]
  2. Kim K.A. Kim D. Kim J.H. Shin Y.J. Kim E.S. Akram M. Kim E.H. Majid A. Baek S.H. Bae O.N. Autophagy-mediated occludin degradation contributes to blood–brain barrier disruption during ischemia in bEnd.3 brain endothelial cells and rat ischemic stroke models. Fluids Barriers CNS 2020 17 1 21 21 10.1186/s12987‑020‑00182‑8 32169114
    [Google Scholar]
  3. Xu M. Wu R.X. Li X.L. Zeng Y.S. Liang J.Y. Fu K. Liang Y. Wang Z. Traditional medicine in China for ischemic stroke: bioactive components, pharmacology, and mechanisms. J. Integr. Neurosci. 2022 21 1 26 26 10.31083/j.jin2101026 35164462
    [Google Scholar]
  4. Shen L. Gan Q. Yang Y. Reis C. Zhang Z. Xu S. Zhang T. Sun C. Mitophagy in cerebral ischemia and ischemia/reperfusion injury. Front. Aging Neurosci. 2021 13 687246 687246 10.3389/fnagi.2021.687246 34168551
    [Google Scholar]
  5. Li P. Chen J.M. Ge S.H. Sun M.L. Lu J.D. Liu F. Wang L.L. Zhang X. Wang X.P. Pentoxifylline protects against cerebral ischaemia-reperfusion injury through ferroptosis regulation via the Nrf2/SLC7A11/GPX4 signalling pathway. Eur. J. Pharmacol. 2024 967 176402 10.1016/j.ejphar.2024.176402 38331339
    [Google Scholar]
  6. Datta A. Sarmah D. Mounica L. Kaur H. Kesharwani R. Verma G. Veeresh P. Kotian V. Kalia K. Borah A. Wang X. Dave K.R. Yavagal D.R. Bhattacharya P. Cell death pathways in Ischemic stroke and targeted pharmacotherapy. Transl. Stroke Res. 2020 11 6 1185 1202 10.1007/s12975‑020‑00806‑z 32219729
    [Google Scholar]
  7. Hitomi E. Simpkins A.N. Luby M. Latour L.L. Leigh R.J. Leigh R. Blood-ocular barrier disruption in patients with acute stroke. Neurology 2018 90 11 e915 e923 10.1212/WNL.0000000000005123 29438039
    [Google Scholar]
  8. Huang Y. Wang X. Guan S. Lin H. Mei Z. Huang Z. Syringin protects against cerebral ischemia and reperfusion injury via suppression of inflammatory mediators and toll-like receptor/MyD88 signaling pathway in rats. Pharmacogn. Mag. 2022 18 77 168 174 10.4103/pm.pm_98_21
    [Google Scholar]
  9. Dong T. Chen N. Ma X. Wang J. Wen J. Xie Q. Ma R. The protective roles of L-borneolum, D-borneolum and synthetic borneol in cerebral ischaemia via modulation of the neurovascular unit. Biomed. Pharmacother. 2018 102 874 883 10.1016/j.biopha.2018.03.087 29728011
    [Google Scholar]
  10. Li Q. Ji Z. Li K. Effect of combination of parenteral edaravone and nimodipine on ischemic cerebral injury following cerebral hemorrhage. Trop. J. Pharm. Res. 2018 17 5 955 955 10.4314/tjpr.v17i5.27
    [Google Scholar]
  11. Ma R. Lu D. Wang J. Xie Q. Guo J. Comparison of pharmacological activity and safety of different stereochemical configurations of borneol: L-borneol, D-borneol, and synthetic borneol. Biomed. Pharmacother. 2023 164 114668 10.1016/j.biopha.2023.114668 37321057
    [Google Scholar]
  12. Zhang W. Wen J. Jiang Y. Hu Q. Wang J. Wei S. Li H. Ma X. l -Borneol ameliorates cerebral ischaemia by downregulating the mitochondrial calcium uniporter-induced apoptosis cascade in pMCAO rats. J. Pharm. Pharmacol. 2021 73 2 272 280 10.1093/jpp/rgaa028 33793797
    [Google Scholar]
  13. Huang D. Awad A. Tang C. Chen Y. Demethylnobiletin ameliorates cerebral ischemia-reperfusion injury in rats through Nrf2/HO-1 signaling pathway. Environ. Toxicol. 2023 39 3 1335 1349 10.1002/tox.24036 37955318
    [Google Scholar]
  14. Hu X. Yan Y. Liu W. Liu J. Fan T. Deng H. Cai Y. Advances and perspectives on pharmacological activities and mechanisms of the monoterpene borneol. Phytomedicine 2024 132 155848 10.1016/j.phymed.2024.155848 38964157
    [Google Scholar]
  15. Yuan Q. Ning L.J. Xin C. Yu H.F. Wen C.H. Wei D.T. Lin J.Z. Exploring the molecular mechanism of Taohong Siwu decoction in the treatment of non-small-cell lung cancer based on network pharmacology and molecular docking. J. Pharm. Pharmacol. 2024 77 6 805 821 10.1093/jpp/rgae141 39680676
    [Google Scholar]
  16. Sho T. Tomohiro I. Akihiro S. Hiroshi M. Masafumi S. Atsuya A. Common carotid occlusion treated with endarterectomy followed by superficial temporal artery–middle cerebral artery bypass. Ann. Vasc. Surg. Brief Rep. Innov. 2023 3 4 100242 10.1016/j.avsurg.2023.100242
    [Google Scholar]
  17. Yin L. Tang T. Lin Y. Yang M. Liu W. Liang S. Functional Connectivity of Ipsilateral Striatum in Rats with Ischemic Stroke Increased by Electroacupuncture. J. Integr. Neurosci. 2022 21 6 162 162 10.31083/j.jin2106162 36424737
    [Google Scholar]
  18. Yuan Y. Sheng P. Ma B. Xue B. Shen M. Zhang L. Li D. Hou J. Ren J. Liu J. Yan B.C. Jiang Y. Elucidation of the mechanism of Yiqi Tongluo Granule against cerebral ischemia/reperfusion injury based on a combined strategy of network pharmacology, multi-omics and molecular biology. Phytomedicine 2023 118 154934 154934 10.1016/j.phymed.2023.154934 37393828
    [Google Scholar]
  19. Cheng Z. Tu J. Wang K. Li F. He Y. Wu W. Wogonin alleviates NLRP3 inflammasome activation after Cerebral Ischemia-Reperfusion injury by regulating AMPK/SIRT1. Brain Res. Bull. 2024 207 110886 10.1016/j.brainresbull.2024.110886 38253131
    [Google Scholar]
  20. Liang X. Wang Z. Wang D. Du J. Qin J. Shen R. Green synthesis, chemical characterization, and protective potentials of silver nanoparticles on the development of cerebrovascular diseases in rat cerebral ischemia reperfusion injury. Inorg. Chem. Commun. 2024 162 112264 10.1016/j.inoche.2024.112264
    [Google Scholar]
  21. Hu X. Mola Y. Su W. Wang Y. Zheng R. Xing J. A network pharmacology approach to decipher the total flavonoid extract of Dracocephalum Moldavica L. in the treatment of Cerebral Ischemia- Reperfusion injury. PLoS One 2023 18 7 e0289118 10.1371/journal.pone.0289118 37494353
    [Google Scholar]
  22. Dong X. Li C. Yao Y. Liu F. Jiang P. Gao Y. Xingnaojing injection alleviates Cerebral Ischemia/Reperfusion injury through regulating endoplasmic reticulum stress in Vivo and in Vitro. Heliyon 2024 10 3 e25267 10.1016/j.heliyon.2024.e25267 38327400
    [Google Scholar]
  23. Hu T. Lin Y. miR-127-5p regulates FAIM2-mediated cell apoptosis and participates in Cerebral Ischemia-Reperfusion injury. Cell. Mol. Biol. 2024 70 2 189 196 10.14715/cmb/2024.70.2.27 38430020
    [Google Scholar]
  24. Elga E. Fang Z. Hyun P. Emiri M. Li W. Isabel C. Ignacio L. Moro M. Lo E. Diurnal differences in immune response in brain, blood and spleen after focal Cerebral Ischemia in mice. Stroke 2022 53 12 e507 e511 10.1161/STROKEAHA.122.040547 36321457
    [Google Scholar]
  25. Jin F. Jin L. Wei B. Li X. Li R. Liu W. Guo S. Fan H. Duan C. miR-96-5p alleviates Cerebral Ischemia-Reperfusion injury in mice by inhibiting pyroptosis via downregulating caspase 1. Exp. Neurol. 2024 374 114676 10.1016/j.expneurol.2024.114676 38190934
    [Google Scholar]
  26. Wang M. Feng Y. Yuan Y. Gui L. Wang J. Gao P. Qin B. Sima D. Wang Q. Pan W. Use of l-3-n-Butylphthalide within 24 h after intravenous thrombolysis for acute cerebral infarction. Complement. Ther. Med. 2020 52 102442 102442 10.1016/j.ctim.2020.102442 32951710
    [Google Scholar]
  27. Xu J. Wang A. Meng X. Yalkun G. Xu A. Gao Z. Chen H. Ji Y. Xu J. Geng D. Zhu R. Liu B. Dong A. Mu H. Lu Z. Li S. Zheng H. Chen X. Wang Y. Zhao X. Wang Y. Wang Y. Xu A. Zhao X. Chen X. Wang Y. Meng X. Wang Y. Xu J. Wang A. Zheng H. Gao Z. Duan L. Zhang J. Li S. Lou D. Gao Z. Chen H. Ji Y. Xu J. Geng D. Zhu R. Liu B. Dong A. Liang Q. Yang H. Guo C. Li X. He M. Tian X. Cui Y. Zhou J. Wang N. Wang L. Zhang X. Gao X. Lu L. Li T. Cheng Y. Liu K. Xi X. Wang B. Sun L. Zhao S. Chu X. Lian Y. Yan F. Wang X. Wang D. Shao B. Jiao J. Wu H. Li G. Guo L. Wang Y. Pan S. Xu A. Li H. Zhuang J. Li X. Wu J. Wang A. Lou D. Zuo Y. Zhang Y. Zhang X. Feng X. Meng X. Wang D. Dong K. Liu Y. Li H. Chen D. Lv Q. TASTE Trial Investigators†. Edaravone dexborneol versus edaravone alone for the treatment of Acute Ischemic Stroke. Stroke 2021 52 3 772 780 10.1161/STROKEAHA.120.031197 33588596
    [Google Scholar]
  28. Ma R. Xie Q. Li H. Guo X. Wang J. Li Y. Ren M. Gong D. Gao T. l-Borneol exerted the neuroprotective effect by promoting Angiogenesis coupled with Neurogenesis via Ang1-VEGF-BDNF Pathway. Front. Pharmacol. 2021 12 641894 641894 10.3389/fphar.2021.641894 33746762
    [Google Scholar]
  29. Zhang Y. You B. Chen Y. Yang J. Xie C. Huang G. Li R. Hu P. Effect of transcriptional regulatory factor FoxO3a on Central Nervous System oxygen toxicity. Front. Physiol. 2020 11 596326 10.3389/fphys.2020.596326 33391015
    [Google Scholar]
  30. Fasano C. Disciglio V. Bertora S. Lepore Signorile M. Simone C. FOXO3a from the nucleus to the mitochondria: A round trip in cellular stress response. Cells 2019 8 9 1110 1110 10.3390/cells8091110 31546924
    [Google Scholar]
  31. Liu Z. Shi Z. Lin J. Zhao S. Hao M. Xu J. Li Y. Zhao Q. Tao L. Diao A. Piperlongumine-induced nuclear translocation of the FOXO3A transcription factor triggers BIM-mediated apoptosis in cancer cells. Biochem. Pharmacol. 2019 163 101 110 10.1016/j.bcp.2019.02.012 30753811
    [Google Scholar]
  32. Abd El-Aal S.A. Abd El-Fattah M.A. El-Abhar H.S. CoQ10 Augments rosuvastatin neuroprotective effect in a model of global ischemia via inhibition of NF-κB/JNK3/Bax and activation of Akt/FOXO3A/Bim Cues. Front. Pharmacol. 2017 8 735 10.3389/fphar.2017.00735 29081748
    [Google Scholar]
  33. Ho K.K. McGuire V.A. Koo C.Y. Muir K.W. de Olano N. Maifoshie E. Kelly D.J. McGovern U.B. Monteiro L.J. Gomes A.R. Nebreda A.R. Campbell D.G. Arthur J.S.C. Lam E.W.F. Phosphorylation of FOXO3a on Ser-7 by p38 promotes its nuclear localization in response to doxorubicin. J. Biol. Chem. 2012 287 2 1545 1555 10.1074/jbc.M111.284224 22128155
    [Google Scholar]
  34. Villa E. Ali E. Sahu U. Ben-Sahra I. Cancer cells tune the signaling pathways to empower de novo synthesis of nucleotides. Cancers 2019 11 5 688 688 10.3390/cancers11050688 31108873
    [Google Scholar]
  35. Wang L. Zhang H. Tang F. Yan H. Feng W. Liu J. Wang Y. Tan Y. Chen H. Therapeutic effects of Valeriana jatamansi on ulcerative Colitis: Insights into mechanisms of action through metabolomics and microbiome analysis. J. Proteome Res. 2023 22 8 2669 2682 10.1021/acs.jproteome.3c00237 37475705
    [Google Scholar]
  36. Song S. Tian B. Zhang M. Gao X. Jie L. Liu P. Li J. Diagnostic and prognostic value of thymidylate synthase expression in breast cancer. Clin. Exp. Pharmacol. Physiol. 2020 48 2 279 287 10.1111/1440‑1681.13415 33030246
    [Google Scholar]
  37. Robinson A.D. Eich M.L. Varambally S. Dysregulation of de novo nucleotide biosynthetic pathway enzymes in cancer and targeting opportunities. Cancer Lett. 2020 470 134 140 10.1016/j.canlet.2019.11.013 31733288
    [Google Scholar]
  38. Wang P. Cui Y. Liu Y. Li Z. Bai H. Zhao Y. Chang Y.Z. Mitochondrial ferritin alleviates apoptosis by enhancing mitochondrial bioenergetics and stimulating glucose metabolism in cerebral ischemia reperfusion. Redox Biol. 2022 57 102475 10.1016/j.redox.2022.102475 36179435
    [Google Scholar]
  39. Zhang Y. Gao S. Xia S. Yang H. Bao X. Zhang Q. Xu Y. Linarin ameliorates ischemia-reperfusion injury by the inhibition of endoplasmic reticulum stress targeting AKR1B1. Brain Res. Bull. 2024 207 110868 10.1016/j.brainresbull.2024.110868 38181967
    [Google Scholar]
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Study on the Mechanism of Anti-Cerebral Ischemia-Reperfusion Injury of Ai Pian Based on Network Pharmacology and Metabolomics
Bentham Science Publishers ; https://doi.org/10.2174/0113892002403752251015105027
/content/journals/cdm/10.2174/0113892002403752251015105027
/content/journals/cdm/10.2174/0113892002403752251015105027
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  • Article Type:     Research Article
Keywords: ischemic stroke ; network pharmacology ; cerebral ischemia-reperfusion injury ; thymidine ; metabolomics ; Ai pian

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