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image of Exploring the Protective Effect and Potential Mechanism of Acutumidine on Myocardial Ischemia based on “Compound-Target-Pathway” Network

Abstract

Introduction

Menispermi Rhizoma is a traditional Chinese medicine with significant Anti-Myocardial Ischemia (MI) effects. Acutumidine is a major alkaloid component of Menispermi Rhizoma. However, the effectiveness and potential mechanism of acutumidine in treating MI have been rarely studied. This research aims to explore the effect and mechanism of acutumidine on MI.

Methods

The function and mechanism of acutumidine in ameliorating MI were investigated a comprehensive strategy of experimental evaluation, network pharmacology, and molecular docking. Firstly, the oxygen glucose deprivation (OGD) model of H9c2 cardiomyocytes was established to confirm the effects of acutumidine on MI. Then, network pharmacology was used to predict the potential targets and mechanisms of acutumidine in MI. The intersection targets between acutumidine and MI were acquired and used to construct a protein-protein interaction network. GO and KEGG enrichment analyses were performed using the Metascape database to reveal the probable mechanism of acutumidine on MI. Finally, the key potential targets of acutumidine were validated by molecular docking.

Results

Cell experiments showed that acutumidine protected H9c2 cells against OGD injury by increasing SOD and GSH levels, decreasing LDH, CK, and MDA levels, and reducing apoptosis rates. Network pharmacology showed that the protective effect of acutumidine on MI was related to PI3K/AKT, HIF-1, and Ras signaling pathways. Molecular docking studies further showed that MAPK1, ESR1, EGFR, IGF1, and CASP3 are the core targets of acutumidine in treating MI.

Discussions

All research results suggested that acutumidine could inhibit oxidative stress and cell apoptosis.

Conclusions

Acutumidine exhibits significant effects on MI, exerting pharmacological effects through multiple targets and pathways.

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2025-09-09
2025-11-08

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References

  1. Pagliaro B.R. Cannata F. Stefanini G.G. Bolognese L. Myocardial ischemia and coronary disease in heart failure. Heart Fail. Rev. 2020 25 1 53 65 10.1007/s10741‑019‑09831‑z 31332663
    [Google Scholar]
  2. Khan M.A.B. Hashim M.J. Mustafa H. Baniyas M.Y. Al Suwaidi S.K.B.M. AlKatheeri R. Alblooshi F.M.K. Almatrooshi M.E.A.H. Alzaabi M.E.H. Al Darmaki R.S. Lootah S.N.A.H. Global epidemiology of ischemic heart disease: Results from the global burden of disease study. Cureus 2020 12 7 e9349 10.7759/cureus.9349 32742886
    [Google Scholar]
  3. Reed G.W. Rossi J.E. Cannon C.P. Acute myocardial infarction. Lancet 2017 389 10065 197 210 10.1016/S0140‑6736(16)30677‑8 27502078
    [Google Scholar]
  4. Marzilli M. Crea F. Morrone D. Bonow R.O. Brown D.L. Camici P.G. Chilian W.M. DeMaria A. Guarini G. Huqi A. Merz C.N.B. Pepine C. Scali M.C. Weintraub W.S. Boden W.E. Myocardial ischemia: From disease to syndrome. Int. J. Cardiol. 2020 314 32 35 10.1016/j.ijcard.2020.04.074 32348810
    [Google Scholar]
  5. Jia S. Liu Y. Yuan J. Evidence in guidelines for treatment of coronary artery disease. Adv. Exp. Med. Biol. 2020 1177 37 73 10.1007/978‑981‑15‑2517‑9_2 32246443
    [Google Scholar]
  6. De Caterina R. Liga R. A treatment algorithm for ischemic cardiomyopathy. Vascul. Pharmacol. 2024 154 107274 10.1016/j.vph.2023.107274 38182081
    [Google Scholar]
  7. Alimirzaei F. Vasheghani-Farahani E. Ghiaseddin A. Soleimani M. pH-sensitive chitosan hydrogel with instant gelation for myocardial regeneration. J. Tissue Sci. Eng. 2017 8 3 1000212
    [Google Scholar]
  8. Jalilinejad N. Rabiee M. Baheiraei N. Ghahremanzadeh R. Salarian R. Rabiee N. Akhavan O. Zarrintaj P. Hejna A. Saeb M.R. Zarrabi A. Sharifi E. Yousefiasl S. Zare E.N. Electrically conductive carbon‐based (bio)‐nanomaterials for cardiac tissue engineering. Bioeng. Transl. Med. 2023 8 1 e10347 10.1002/btm2.10347 36684103
    [Google Scholar]
  9. Tajabadi M. Goran Orimi H. Ramzgouyan M.R. Nemati A. Deravi N. Beheshtizadeh N. Azami M. Regenerative strategies for the consequences of myocardial infarction: Chronological indication and upcoming visions. Biomed. Pharmacother. 2022 146 112584 10.1016/j.biopha.2021.112584 34968921
    [Google Scholar]
  10. Hagège A.A. Vilquin J.T. Bruneval P. Menasché P. Regeneration of the Myocardium. Hypertension 2001 38 6 1413 1415 10.1161/hy1201.099618 11751727
    [Google Scholar]
  11. Yang H.Y. Liu M.L. Luo P. Yao X.S. Zhou H. Network pharmacology provides a systematic approach to understanding the treatment of ischemic heart diseases with traditional Chinese medicine. Phytomedicine 2022 104 154268 10.1016/j.phymed.2022.154268 35777118
    [Google Scholar]
  12. Yu Y.Y. Shao J. Chen F. Zhang T.T. Wei J.X. Li L.Z. Study on oxoisoaporphine alkaloids from rhizome of Menispermi Rhizoma and their anti-myocardial ischemia activities. J. Logist Unive Pap 2019 28 11 1 6
    [Google Scholar]
  13. Wei J. Yu Y. Zhang Y. Li L. Li X. Shao J. Li Y. Integrated serum pharmacochemistry and network pharmacology approach to explore the effective components and potential mechanisms of Menispermi Rhizoma against myocardial ischemia. Front Chem. 2022 10 869972 10.3389/fchem.2022.869972 35665070
    [Google Scholar]
  14. Wei J. Cui K. Du Y. Yu J. Jiang Z. Guo X. Rapid and simultaneous determination of 22 constituents in Menispermi Rhizoma by ultra-performance liquid chromatography tandem triple quadrupole mass spectrometry. Anal. Methods 2017 9 20 3029 3038 10.1039/C7AY00559H
    [Google Scholar]
  15. Wei J. Fang L. Liang X. Su D. Guo X. A sensitive and selective UPLC–MS/MS method for simultaneous determination of 10 alkaloids from Rhizoma Menispermi in rat plasma and its application to a pharmacokinetic study. Talanta 2015 144 662 670 10.1016/j.talanta.2015.07.023 26452875
    [Google Scholar]
  16. Shao J. Shi C.F. Wei J.X. Li Y.X. Guo X.J. Chemical constituents from rhizome of Menispermum dauricum and their anti-hypoxic activities. Zhongguo Zhongyao Zazhi 2019 44 4 723 729 30989885
    [Google Scholar]
  17. Li X. Liu Z. Liao J. Chen Q. Lu X. Fan X. Network pharmacology approaches for research of Traditional Chinese Medicines. Chin. J. Nat. Med. 2023 21 5 323 332 10.1016/S1875‑5364(23)60429‑7 37245871
    [Google Scholar]
  18. Rad M. Ebrahimipour G. Bandehpour M. Akhavan O. Yarian F. SOEing PCR/Docking optimization of protein A-G/scFv-Fc-bioconjugated Au nanoparticles for interaction with meningitidis bacterial antigen. Catalysts 2023 13 5 790 10.3390/catal13050790
    [Google Scholar]
  19. Ji L. Song T. Ge C. Wu Q. Ma L. Chen X. Chen T. Chen Q. Chen Z. Chen W. Identification of bioactive compounds and potential mechanisms of scutellariae radix-coptidis rhizoma in the treatment of atherosclerosis by integrating network pharmacology and experimental validation. Biomed. Pharmacother. 2023 165 115210 10.1016/j.biopha.2023.115210 37499457
    [Google Scholar]
  20. Liu X. Sun P. Bao X. Cao Y. Wang L. Wang Q. Potential mechanisms of traditional Chinese medicine in treating insomnia: A network pharmacology, GEO validation, and molecular-docking study. Medicine (Baltimore) 2024 103 18 e38052 10.1097/MD.0000000000038052 38701256
    [Google Scholar]
  21. Lai Q. Wu L. Dong S. Zhu X. Fan Z. Kou J. Liu F. Yu B. Li F. Inhibition of KMO ameliorates myocardial ischemia injury via maintaining mitochondrial fusion and fission balance. Int. J. Biol. Sci. 2023 19 10 3077 3098 10.7150/ijbs.83392 37416768
    [Google Scholar]
  22. Chen L. Li S. Zhu J. You A. Huang X. Yi X. Xue M. Mangiferin prevents myocardial infarction‐induced apoptosis and heart failure in mice by activating the Sirt1/FoxO3a pathway. J. Cell. Mol. Med. 2021 25 6 2944 2955 10.1111/jcmm.16329 33523605
    [Google Scholar]
  23. Yu Y. Shao J. Chen F. Zhang T. Wei J. Li L. Study on oxoisoaporphine alkaloids from rhizome of Menispermum dauricum and their anti-myocardial ischemia activities. J. Logist. Univer. PAP 2019 28 11 1 6
    [Google Scholar]
  24. van der Pol A. van Gilst W.H. Voors A.A. van der Meer P. Treating oxidative stress in heart failure: Past, present and future. Eur. J. Heart Fail. 2019 21 4 425 435 10.1002/ejhf.1320 30338885
    [Google Scholar]
  25. Su Y.M. Li Y.Q. Research on protective effects of phenolic alkaloid of Menispermum Dauricum on experimental myocardial ischemia. China Pharmacist 2002 6 5 326 328
    [Google Scholar]
  26. Li H. Bu L. Sun X. Chu X. Xue Y. Zhang M. Shi J. Liu Y. Guan S. Han X. Wang H. Mechanistic investigation of the ameliorative effect of liquiritin on hypoxia/reoxygenation induced cardiomyocyte injury based on network pharmacology and in vitro validation. Exp. Ther. Med. 2024 27 3 117 10.3892/etm.2024.12405 38361515
    [Google Scholar]
  27. Ghormade P.S. Kumar N.B. Tingne C.V. Keoliya A.N. Distribution & diagnostic efficacy of cardiac markers CK-MB & LDH in pericardial fluid for postmortem diagnosis of ischemic heart disease. J. Forensic Leg. Med. 2014 28 42 46 10.1016/j.jflm.2014.09.011 25440147
    [Google Scholar]
  28. Farías J. Molina V. Carrasco R. Zepeda A. Figueroa E. Letelier P. Castillo R. Antioxidant therapeutic strategies for cardiovascular conditions associated with oxidative stress. Nutrients 2017 9 9 966 10.3390/nu9090966 28862654
    [Google Scholar]
  29. Jiang R.B. Zhu X.X. Xing L.W. Ding Z.S. Lv G.Y. Jin B. Protective effect of total flavonoids from Carya cathayensis Leaf on cultured H9c2 cardiomyocytes during hypoxia/reoxygenation injury. Zhong Yao Cai 2016 39 2 378 382 30080372
    [Google Scholar]
  30. Zhao J. Xu J. Liu J. Clinical efficacy analysis of hyperbaric oxygen combined with Liraglutide and Jianpi Huatan Formula in treating early type 2 diabetic retinopathy. Chin J. Naut. Med. Hyperbar Med. 2021 28 03 330 335
    [Google Scholar]
  31. Amani H. Habibey R. Shokri F. Hajmiresmail S.J. Akhavan O. Mashaghi A. Pazoki-Toroudi H. Selenium nanoparticles for targeted stroke therapy through modulation of inflammatory and metabolic signaling. Sci. Rep. 2019 9 1 6044 10.1038/s41598‑019‑42633‑9 30988361
    [Google Scholar]
  32. Amani H. Habibey R. Hajmiresmail S.J. Latifi S. Pazoki-Toroudi H. Akhavan O. Antioxidant nanomaterials in advanced diagnoses and treatments of ischemia reperfusion injuries. J. Mater. Chem. B Mater. Biol. Med. 2017 5 48 9452 9476 10.1039/C7TB01689A 32264560
    [Google Scholar]
  33. Ajith T.A. Jayakumar T.G. Mitochondria-targeted agents: Future perspectives of mitochondrial pharmaceutics in cardiovascular diseases. World J. Cardiol. 2014 6 10 1091 1099 10.4330/wjc.v6.i10.1091 25349653
    [Google Scholar]
  34. Zhang Q. Wu X. Yang J. miR-194-5p protects against myocardial ischemia/reperfusion injury via MAPK1/PTEN/AKT pathway. Ann. Transl. Med. 2021 9 8 654 10.21037/atm‑21‑807 33987352
    [Google Scholar]
  35. Chen S. Li Y. Yang F. Tan M. Song L. Tan J. Yishen Tongluo interferes with renal tubular epithelial cell apoptosis in membranous nephropathy by down-regulating ADAM17-mediated EGFR expression. Chin. Tradit. Herbal Drugs 2021 52 24 7520 7526
    [Google Scholar]
  36. Liang D. Zhong P. Hu J. Lin F. Qian Y. Xu Z. Wang J. Zeng C. Li X. Liang G. EGFR inhibition protects cardiac damage and remodeling through attenuating oxidative stress in STZ-induced diabetic mouse model. J. Mol. Cell. Cardiol. 2015 82 63 74 10.1016/j.yjmcc.2015.02.029 25758431
    [Google Scholar]
  37. Rahimnejad M. Nasrollahi Boroujeni N. Jahangiri S. Rabiee N. Rabiee M. Makvandi P. Akhavan O. Varma R.S. Prevascularized Micro-/Nano-Sized Spheroid/bead aggregates for vascular tissue engineering. Nano-Micro Lett. 2021 13 1 182 10.1007/s40820‑021‑00697‑1 34409511
    [Google Scholar]
  38. Puzianowska-Kuźnicka M. ESR1 in myocardial infarction. Clin. Chim. Acta 2012 413 1-2 81 87 10.1016/j.cca.2011.10.028 22061094
    [Google Scholar]
  39. Fan J. Shi S. Qiu Y. Zheng Z. Yu L. MicroRNA-486-5p down-regulation protects cardiomyocytes against hypoxia-induced cell injury by targeting IGF-1. Int. J. Clin. Exp. Pathol. 2019 12 7 2544 2551 31934081
    [Google Scholar]
  40. Mao Q. Shao C. Zhou H. Yu L. Bao Y. Zhao Y. Yang J. Wan H. Exploring the mechanism of salvianolic Acid B against myocardial ischemia-reperfusion injury based on network pharmacology. Pharmaceuticals 2024 17 3 309 10.3390/ph17030309 38543095
    [Google Scholar]
  41. Lu C. Ha T. Wang X. Liu L. Zhang X. Kimbrough E.O. Sha Z. Guan M. Schweitzer J. Kalbfleisch J. Williams D. Li C. The TLR9 ligand, CpG-ODN, induces protection against cerebral ischemia/reperfusion injury via activation of PI3K/Akt signaling. J. Am. Heart Assoc. 2014 3 2 e000629 10.1161/JAHA.113.000629 24721797
    [Google Scholar]
  42. Lu Y. Lin J. Duan M. Rui Y. Zheng H. Zhu L. Zhu X. Wei J. Anlotinib suppresses oral squamous cell carcinoma growth and metastasis by targeting the RAS protein to inhibit the PI3K/Akt signalling pathway. Anal. Cell. Pathol. (Amst.) 2021 2021 1 9 10.1155/2021/5228713 34926131
    [Google Scholar]
  43. Chen Z. Wang C. Yu N. Si L. Zhu L. Zeng A. Liu Z. Wang X. INF2 regulates oxidative stress-induced apoptosis in epidermal HaCaT cells by modulating the HIF1 signaling pathway. Biomed. Pharmacother. 2019 111 151 161 10.1016/j.biopha.2018.12.046 30579254
    [Google Scholar]
  44. Xing N. Qin J. Ren D. Du Q. Li Y. Mi J. Zhang F. Ai L. Zhang S. Zhang Y. Wang S. Integrating UPLC-Q-Exactive Orbitrap/MS, network pharmacology and experimental validation to reveal the potential mechanism of Tibetan medicine Rhodiola granules in improving myocardial ischemia-reperfusion injury. J. Ethnopharmacol. 2023 314 116572 10.1016/j.jep.2023.116572 37201662
    [Google Scholar]
  45. Wang T. Xiao Y. Zhang J. Jing F. Zeng G. Dynamic regulation of HIF-1 signaling in the rhesus monkey heart after ischemic injury. BMC Cardiovasc. Disord. 2022 22 1 407 10.1186/s12872‑022‑02841‑0 36089604
    [Google Scholar]
  46. Hou T. Ma H. Wang H. Chen C. Ye J. Ahmed A.M. Zheng H. Sevoflurane preconditioning attenuates hypoxia/reoxygenation injury of H9c2 cardiomyocytes by activation of the HIF-1/PDK-1 pathway. PeerJ 2020 8 e10603 10.7717/peerj.10603 33391885
    [Google Scholar]
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Exploring the Protective Effect and Potential Mechanism of Acutumidine on Myocardial Ischemia based on “Compound-Target-Pathway” Network
Bentham Science Publishers ; https://doi.org/10.2174/0113862073399707250827110100
/content/journals/cchts/10.2174/0113862073399707250827110100
/content/journals/cchts/10.2174/0113862073399707250827110100
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  • Article Type:     Research Article
Keywords: myocardial ischemia ; molecular docking ; cell experiment ; network pharmacology ; PI3K/AKT signaling pathway ; Acutumidine

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