Skip to main content

Advertisement

SpringerLink
Log in

Current Updates on Potential Role of Flavonoids in Hypoxia/Reoxygenation Cardiac Injury Model

  • Published:
Cardiovascular Toxicology Aims and scope Submit manuscript

Abstract

Clinically, timely reperfusion strategies to re-establish oxygenated blood flow in ischemic heart diseases seem to salvage viable myocardium effectively. Despite the remarkable improvement in cardiac function, reperfusion therapy could paradoxically trigger hypoxic cellular injury and dysfunction. Experimental laboratory models have been developed over the years to explain better the pathophysiology of cardiac ischemia–reperfusion injury, including the in vitro hypoxia-reoxygenation cardiac injury model. Furthermore, the use of nutritional myocardial conditioning techniques have been successful. The cardioprotective potential of flavonoids have been greatly linked to its anti-oxidant, anti-apoptotic and anti-inflammatory properties. While several studies have reviewed the cardioprotective properties of flavonoids, there is a scarce evidence of their function in the hypoxia-reoxygenation injury cell culture model. Hence, the aim of this review was to lay out and summarize our current understanding of flavonoids’ function in mitigating hypoxia-reoxygenation cardiac injury based on evidence from the last five years. We also discussed the possible mechanisms of flavonoids in modulating the cardioprotective effects as such information would provide invaluable insight on future therapeutic application of flavonoids.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. World Health Organization. (2021). Cardiovascular diseases. https://www.who.int/health-topics/cardiovascular-diseases

  2. Ministry of Health Malaysia. (2020). The impact of noncommunicable diseases and their risk factors on Malaysia’s gross domestic product.

  3. McDougal, A. D., & Dewey, C. F., Jr. (2017). Modeling oxygen requirements in ischemic cardiomyocytes. Journal of Biological Chemistry, 292(28), 11760–11776. https://doi.org/10.1074/jbc.M116.751826

    Article  CAS  Google Scholar 

  4. Severino, P., D’Amato, A., Pucci, M., Infusino, F., Adamo, F., Birtolo, L. I., Netti, L., Montefusco, G., Chimenti, C., Lavalle, C., & Maestrini, V. (2020). Ischemic heart disease pathophysiology paradigms overview: From plaque activation to microvascular dysfunction. International Journal of Molecular Sciences, 21(21), 8118. https://doi.org/10.3390/ijms21218118

    Article  CAS  PubMed Central  Google Scholar 

  5. Katz, D., & Gavin, M. C. (2019). Stable ischemic heart disease. Annals of Internal Medicine, 171(3), 8060.

    Article  Google Scholar 

  6. Wu, M. Y., Yiang, G. T., Liao, W. T., Tsai, A. P. Y., Cheng, Y. L., Cheng, P. W., Li, C. Y., & Li, C. J. (2018). Current mechanistic concepts in ischemia and reperfusion injury. Cellular Physiology and Biochemistry, 46(4), 1650–1667. https://doi.org/10.1159/000489241

    Article  CAS  PubMed  Google Scholar 

  7. Cowled, P., & Fitridge, R. (2011). Mechanisms of vascular disease: Pathophysiology of reperfusion injury. Adelaide (AU): University of Adelaide Press.

    Google Scholar 

  8. Neri, M., Riezzo, I., Pascale, N., Pomara, C., & Turillazzi, E. (2017). Ischemia/reperfusion injury following acute myocardial infarction: A critical issue for clinicians and forensic pathologists. Mediators of Inflammation, 2017, 7018393. https://doi.org/10.1155/2017/7018393

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Chakraborti, S., Dhalla, N. S., Dikshit, M., & Ganguly, N. K. (2019). Modulation of oxidative stress in heart disease. Singapore: Springer.

    Book  Google Scholar 

  10. Lindsey, M. L., Bolli, R., Canty, J. M., Jr., Du, X. J., Frangogiannis, N. G., Frantz, S., Gourdie, R. G., Holmes, J. W., Jones, S. P., Kloner, R. A., & Lefer, D. J. (2018). Guidelines for experimental models of myocardial ischemia and infarction. American Journal of Physiology, 314(4), H812–H838. https://doi.org/10.1152/ajpheart.00335.2017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Donato, M., Evelson, P., & Gelpi, R. J. (2017). Protecting the heart from ischemia/reperfusion injury: An update on remote ischemic preconditioning and postconditioning. Current Opinion in Cardiology, 32(6), 784–790. https://doi.org/10.1097/HCO.0000000000000447

    Article  PubMed  Google Scholar 

  12. Da Zhou, J. D., Ya, J., Pan, L., Wang, Y., Ji, X., & Meng, R. (2018). Remote ischemic conditioning: A promising therapeutic intervention for multi-organ protection. Aging, 10(8), 1825. https://doi.org/10.18632/aging.101527

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Jiang, H., Xing, J., Fang, J., Wang, L., Wang, Y., Zeng, L., Li, Z., & Liu, R. (2020). Tilianin Protects against ischemia/reperfusion-induced myocardial injury through the inhibition of the Ca2+/calmodulin-dependent protein kinase II-dependent apoptotic and inflammatory signalling pathways. BioMed Research International, 2020, 5939715. https://doi.org/10.1155/2020/5939715

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Liu, G., Zhang, B. F., Hu, Q., Liu, X. P., & Chen, J. (2020). Syringic acid mitigates myocardial ischemia reperfusion injury by activating the PI3K/Akt/GSK-3β signalling pathway. Biochemical and Biophysical Research Communications, 531(2), 242–249. https://doi.org/10.1016/j.bbrc.2020.07.047

    Article  CAS  PubMed  Google Scholar 

  15. Yao, X., Jiao, S., Qin, M., Hu, W., Yi, B., & Liu, D. (2020). Vanillic acid alleviates acute myocardial hypoxia/reoxygenation injury by inhibiting oxidative stress. Oxidative Medicine and. Cellular Longevity, 2020, 8348035. https://doi.org/10.1155/2020/8348035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Wang, M., Liu, Y., Pan, R. L., Wang, R. Y., Ding, S. L., Dong, W. R., Sun, G. B., Ye, J. X., & Sun, X. B. (2019). Protective effects of Myrica rubra flavonoids against hypoxia/reoxygenation-induced cardiomyocyte injury via the regulation of the PI3K/Akt/GSK3β pathway. International Journal of Molecular Medicine, 43(5), 2133–2143. https://doi.org/10.3892/ijmm.2019.4131

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Yang, P., Zhou, Y., Xia, Q., Yao, L., & Chang, X. (2019). Astragaloside IV regulates the PI3K/Akt/HO-1 signalling pathway and inhibits H9c2 cardiomyocyte injury induced by hypoxia–reoxygenation. Biological and Pharmaceutical Bulletin, 42(5), 721–727. https://doi.org/10.1248/bpb.b18-00854

    Article  CAS  PubMed  Google Scholar 

  18. Wu, W. Y., Li, Y. D., Cui, Y. K., Wu, C., Hong, Y. X., Li, G., Wu, Y., Jie, L. J., Wang, Y., & Li, G. R. (2018). The natural flavone acacetin confers cardiomyocyte protection against hypoxia/reoxygenation injury via AMPK-mediated activation of Nrf2 signalling pathway. Frontiers in Pharmacology, 9, 497. https://doi.org/10.3389/fphar.2018.00497

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Zhang, H. J., Chen, R. C., Sun, G. B., Yang, L. P., Xu, X. D., & Sun, X. B. (2018). Protective effects of total flavonoids from Clinopodium chinense (Benth.) O. Ktze on myocardial injury in vivo and in vitro via regulation of Akt/Nrf2/HO-1 pathway. Phytomedicine, 40, 88–97. https://doi.org/10.1016/j.phymed.2018.01.004

    Article  CAS  PubMed  Google Scholar 

  20. Ali, S. S., Ahmad, W. A. N. W., Budin, S. B., & Zainalabidin, S. (2020). Implication of dietary phenolic acids on inflammation in cardiovascular disease. Reviews in Cardiovascular Medicine, 21(2), 225–240. https://doi.org/10.31083/j.rcm.2020.02.49

    Article  PubMed  Google Scholar 

  21. Mulvihill, E. E., Burke, A. C., & Huff, M. W. (2016). Citrus flavonoids as regulators of lipoprotein metabolism and atherosclerosis. Annual Review of Nutrition, 36, 275–299. https://doi.org/10.1146/annurev-nutr-071715-050718

    Article  CAS  PubMed  Google Scholar 

  22. Marunaka, Y., Marunaka, R., Sun, H., Yamamoto, T., Kanamura, N., Inui, T., & Taruno, A. (2017). Actions of quercetin, a polyphenol, on blood pressure. Molecules, 22(2), 209. https://doi.org/10.3390/molecules22020209

    Article  CAS  PubMed Central  Google Scholar 

  23. Eng, Q. Y., Thanikachalam, P. V., & Ramamurthy, S. (2018). Molecular understanding of Epigallocatechin gallate (EGCG) in cardiovascular and metabolic diseases. Journal of Ethnopharmacology, 210, 296–310. https://doi.org/10.1016/j.jep.2017.08.035

    Article  CAS  PubMed  Google Scholar 

  24. Choy, K. W., Murugan, D., Leong, X. F., Abas, R., Alias, A., & Mustafa, M. R. (2019). Flavonoids as natural anti-inflammatory agents targeting nuclear factor-kappa B (NFκB) signalling in cardiovascular diseases: A mini review. Frontiers in Pharmacology, 10, 1295. https://doi.org/10.3389/fphar.2019.01295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Ciumărnean, L., Milaciu, M. V., Runcan, O., Vesa, ȘC., Răchișan, A. L., Negrean, V., Perné, M. G., Donca, V. I., Alexescu, T. G., Para, I., & Dogaru, G. (2020). The effects of flavonoids in cardiovascular diseases. Molecules, 25(18), 4320. https://doi.org/10.3390/molecules25184320

    Article  CAS  PubMed Central  Google Scholar 

  26. Rufino, A. T., Costa, V. M., Carvalho, F., & Fernandes, E. (2021). Flavonoids as antiobesity agents: A review. Medicinal Research Reviews, 41(1), 556–585. https://doi.org/10.1002/med.21740

    Article  CAS  PubMed  Google Scholar 

  27. Son, E., Lee, D., Woo, C. W., & Kim, Y. H. (2020). The optimal model of reperfusion injury in vitro using H9c2 transformed cardiac myoblasts. Korean Journal of Physiology Pharmacology, 24(2), 173. https://doi.org/10.4196/kjpp.2020.24.2.173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Gerő, D. (2017). Hypoxia and human diseases: The hypoxia-reoxygenation injury model. Intech Open, 47, 65339.

    Google Scholar 

  29. Kuznetsov, A. V., Javadov, S., Sickinger, S., Frotschnig, S., & Grimm, M. (2015). H9c2 and HL-1 cells demonstrate distinct features of energy metabolism, mitochondrial function and sensitivity to hypoxia-reoxygenation. Biochimica et Biophysica Acta, Molecular Cell Research, 1853(2), 276–284. https://doi.org/10.1016/j.bbamcr.2014.11.015

    Article  CAS  Google Scholar 

  30. Pavlacky, J., & Polak, J. (2020). Technical feasibility and physiological relevance of hypoxic cell culture models. Frontiers in Endocrinology, 11, 57. https://doi.org/10.3389/fendo.2020.00057

    Article  PubMed  PubMed Central  Google Scholar 

  31. Sayed, N., Tambe, P., Kumar, P., Jadhav, S., Paknikar, K. M., & Gajbhiye, V. (2020). miRNA transfection via poly (amidoamine)-based delivery vector prevents hypoxia/reperfusion-induced cardiomyocyte apoptosis. Nanomedicine, 15(2), 163–181. https://doi.org/10.2217/nnm-2019-0363

    Article  CAS  PubMed  Google Scholar 

  32. Teti, G., Focaroli, S., Salvatore, V., Mazzotti, E., Ingra, L., Mazzotti, A., & Falconi, M. (2018). (2018) The hypoxia-mimetic agent cobalt chloride differently affects human mesenchymal stem cells in their chondrogenic potential. Stem Cells International, 2018, 3237253. https://doi.org/10.1155/2018/3237253

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Jennings, R. Á. (1960). Myocardial necrosis induced by temporary occulusion of a coronary artery in the dog. Archives of Pathology, 70, 68–70.

    CAS  PubMed  Google Scholar 

  34. Douzinas, E. E., & Apeiranthitis, A. (2019). Modulation of oxidative stress in heart disease: basic mechanisms of ischemia/reperfusion injury leading to cellular and tissue damage: Therapeutic implications. Singapore: Springer.

    Google Scholar 

  35. Eltzschig, H. K., & Eckle, T. (2011). Ischemia and reperfusion—from mechanism to translation. Nature Medicine, 17(11), 1391–1401. https://doi.org/10.1038/nm.2507

    Article  CAS  PubMed  Google Scholar 

  36. Frank, A., Bonney, M., Bonney, S., Weitzel, L., Koeppen, M., & Eckle, T. (2012) Myocardial ischemia-reperfusion injury: From basic science to clinical bedside. Seminars in Cardiothoracic and Vascular Anesthesia, 16(3), 123–132. https://doi.org/10.1177/1089253211436350

  37. Yang, C. F. (2018). Clinical manifestations and basic mechanisms of myocardial ischemia/reperfusion injury. Tzu-Chi Med. J., 30(4), 209. https://doi.org/10.4103/tcmj.tcmj_33_18

    Article  PubMed Central  Google Scholar 

  38. Kurian, G. A., Rajagopal, R., Vedantham, S., & Rajesh, M. (2016). The role of oxidative stress in myocardial ischemia and reperfusion injury and remodeling: revisited. Oxidative Medicine and Cellular Longevity, 2016, 1656450. https://doi.org/10.1155/2016/1656450

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Jubaidi, F. F., Zainalabidin, S., Mariappan, V., & Budin, S. B. (2020). Mitochondrial dysfunction in diabetic cardiomyopathy: The possible therapeutic roles of phenolic acids. International Journal of Molecular Sciences, 21(17), 6043. https://doi.org/10.3390/ijms21176043

    Article  CAS  PubMed Central  Google Scholar 

  40. Dias, A. E. M. S. Á. S., Melnikov, P., & Cônsolo, L. Z. Z. (2015). Oxidative stress in coronary artery bypass surgery. Brazilian Journal of Cardiovascular Surgery, 30(4), 417–424. https://doi.org/10.5935/1678-9741.20150052

    Article  PubMed  PubMed Central  Google Scholar 

  41. Liu, J., Hou, J., Xia, Z. Y., Zeng, W., Wang, X., Li, R., Ke, C., Xu, J., Lei, S., & Xia, Z. (2013). Recombinant PTD-Cu/Zn SOD attenuates hypoxia–reoxygenation injury in cardiomyocytes. Free Rad. Res., 47(5), 386–393. https://doi.org/10.3109/10715762.2013.780286

    Article  CAS  Google Scholar 

  42. Pei, H., Yang, Y., Zhao, H., Li, X., Yang, D., Li, D., & Yang, Y. (2016). The role of mitochondrial functional proteins in ROS production in ischemic heart diseases. Oxidative Medicine and Cellular Longevity, 2016, 5470457. https://doi.org/10.1155/2016/5470457

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Hausenloy, D. J., & Yellon, D. M. (2013). Myocardial ischemia-reperfusion injury: A neglected therapeutic target. The Journal of Clinical Investigation, 123(1), 92–100. https://doi.org/10.1172/JCI62874

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Barkhade, T., Mahapatra, S. K., & Banerjee, I. (2019). Study of mitochondrial swelling, membrane fluidity and ROS production induced by nano-TiO2 and prevented by Fe incorporation. Toxicology Research, 8(5), 711–722. https://doi.org/10.1039/C9TX00143C

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Zhang, C. X., Cheng, Y., Liu, D. Z., Liu, M., Cui, H., Mei, Q. B., & Zhou, S. Y. (2019). Mitochondria-targeted cyclosporin A delivery system to treat myocardial ischemia reperfusion injury of rats. Journal of Nanobiotechnology, 17(1), 1–16. https://doi.org/10.1186/s12951-019-0451-9

    Article  Google Scholar 

  46. Gendron, A., Lan, L., Tran, N., Laloy, J., Brusini, R., Rachet, A., Gobeaux, F., Nicolas, V., Chaminade, P., Abreu, S., Desmaële, D., & Varna, M. (2021). New nanoparticle formulation for cyclosporin A: In vitro assessment. Pharmaceutics, 13(1), 91. https://doi.org/10.3390/pharmaceutics13010091

    Article  PubMed  PubMed Central  Google Scholar 

  47. González-Montero, J., Brito, R., Gajardo, A. I., & Rodrigo, R. (2018). Myocardial reperfusion injury and oxidative stress: Therapeutic opportunities. World Journal of Cardiology, 10(9), 74. https://doi.org/10.4330/wjc.v10.i9.74

    Article  PubMed  PubMed Central  Google Scholar 

  48. He, X., Li, S., Fang, X., & Liao, Y. (2018). TDCPP protects cardiomyocytes from hypoxia-reoxygenation injury induced apoptosis through mitigating calcium overload and promotion GSK-3β phosphorylation. Regulatory Toxicology and Pharmacology, 92, 39–45. https://doi.org/10.1016/j.yrtph.2017.11.005

    Article  CAS  PubMed  Google Scholar 

  49. Landstrom, A. P., Dobrev, D., & Wehrens, X. H. (2017). Calcium signalling and cardiac arrhythmias. Circulation Research, 120(12), 1969–1993. https://doi.org/10.1161/CIRCRESAHA.117.310083

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Pittas, K., Vrachatis, D. A., Angelidis, C., Tsoucala, S., Giannopoulos, G., & Deftereos, S. (2018). The role of calcium handling mechanisms in reperfusion injury. Current Pharmaceutical Design, 24(34), 4077–4089. https://doi.org/10.2174/1381612825666181120155953

    Article  CAS  PubMed  Google Scholar 

  51. Garcia-Dorado, D., Ruiz-Meana, M., Inserte, J., Rodriguez-Sinovas, A., & Piper, H. M. (2012). Calcium-mediated cell death during myocardial reperfusion. Cardiovascular Research, 94(2), 168–180. https://doi.org/10.1093/cvr/cvs116

    Article  CAS  PubMed  Google Scholar 

  52. Kalogeris, T., Baines, C. P., Krenz, M., & Korthuis, R. J. (2012). Cell biology of ischemia/reperfusion injury. International Review of Cell and Molecular Biology, 298, 229–317. https://doi.org/10.1016/B978-0-12-394309-5.00006-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Minato, H., Hisatome, I., Kurata, Y., Notsu, T., Nakasone, N., Ninomiya, H., Hamada, T., Tomomori, T., Okamura, A., Miake, J., & Tsuneto, M. (2020). Pretreatment with cilnidipine attenuates hypoxia/reoxygenation injury in HL-1 cardiomyocytes through enhanced NO production and action potential shortening. Hyperten. Res., 43(5), 380–388. https://doi.org/10.1038/s41440-019-0391-7

    Article  CAS  Google Scholar 

  54. Mahmoud, A. M., Hernandez Bautista, R. J., Sandhu, M. A., & Hussein, O. E. (2019). Beneficial effects of citrus flavonoids on cardiovascular and metabolic health. Oxidative Medicine and Cellular Longevity, 2019, 548413. https://doi.org/10.1155/2019/5484138

    Article  CAS  Google Scholar 

  55. Xiao, J. (2017). Dietary flavonoid aglycones and their glycosides: Which show better biological significance? Critical Reviews in Food Science and Nutrition, 57(9), 1874–1905. https://doi.org/10.1080/10408398.2015.1032400

    Article  CAS  PubMed  Google Scholar 

  56. Abbas, M., Saeed, F., Anjum, F. M., Afzaal, M., Tufail, T., Bashir, M. S., Ishtiaq, A., Hussain, S., & Suleria, H. A. R. (2017). Natural polyphenols: An overview. International Journal of Food Properties, 20(8), 1689–1699. https://doi.org/10.1080/10942912.2016.1220393

    Article  CAS  Google Scholar 

  57. Crozier, A., Del Rio, D., & Clifford, M. N. (2010). Bioavailability of dietary flavonoids and phenolic compounds. Molecular Aspects of Medicine, 31(6), 446–467. https://doi.org/10.1016/j.mam.2010.09.007

    Article  CAS  PubMed  Google Scholar 

  58. Murota, K., Nakamura, Y., & Uehara, M. (2018). Flavonoid metabolism: The interaction of metabolites and gut microbiota. Bioscience Biotechnology Biochemistry, 82(4), 600–610. https://doi.org/10.1080/09168451.2018.1444467

    Article  CAS  Google Scholar 

  59. Zhao, J., Yang, J., & Xie, Y. (2019). Improvement strategies for the oral bioavailability of poorly water-soluble flavonoids: An overview. International Journal of Pharmaceutics, 570, 118642. https://doi.org/10.1016/j.ijpharm.2019.118642

    Article  CAS  PubMed  Google Scholar 

  60. Hostetler, G. L., Ralston, R. A., & Schwartz, S. J. (2017). Flavones: Food sources, bioavailability, metabolism, and bioactivity. Advances in Nutrition, 8(3), 423–435. https://doi.org/10.3945/an.116.012948

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Qiao, Z., Xu, Y. W., & Yang, J. (2016). Eupatilin inhibits the apoptosis in H9c2 cardiomyocytes via the Akt/GSK-3β pathway following hypoxia/reoxygenation injury. Biomedicine Pharmatherapy, 82, 373–378. https://doi.org/10.1016/j.biopha.2016.05.026

    Article  CAS  Google Scholar 

  62. Gallyas, F., Jr., Sumegi, B., & Szabo, C. (2020). Role of Akt activation in PARP inhibitor resistance in cancer. Cancers, 12(3), 532. https://doi.org/10.3390/cancers12030532

    Article  CAS  PubMed Central  Google Scholar 

  63. Tang, J. Y., Jin, P., He, Q., Lu, L. H., Ma, J. P., Gao, W. L., Bai, H. P., & Yang, J. (2017). Naringenin ameliorates hypoxia/reoxygenation-induced endoplasmic reticulum stress-mediated apoptosis in H9c2 myocardial cells: Involvement in ATF6, IRE1α and PERK signalling activation. Molecular and Cellular Biochemistry, 424(1–2), 111–122. https://doi.org/10.1007/s11010-016-2848-1

    Article  CAS  PubMed  Google Scholar 

  64. Liu, L., Wu, Y., & Huang, X. (2016). Orientin protects myocardial cells against hypoxia-reoxygenation injury through induction of autophagy. European Journal of Pharmacology, 776, 90–98. https://doi.org/10.1016/j.ejphar.2016.02.037

    Article  CAS  PubMed  Google Scholar 

  65. Wu, W. Y., Li, Y. D., Cui, Y. K., Wu, C., Hong, Y. X., Li, G., Wu, Y., Jie, L. J., Wang, Y., & Li, G. R. (2019). The natural flavone acacetin confers cardiomyocyte protection against hypoxia/reoxygenation injury via AMPK-mediated activation of Nrf2 signalling pathway. Frontiers in Pharmacology, 9, 497. https://doi.org/10.3389/fphar.2018.00497

    Article  CAS  Google Scholar 

  66. Pang, J. J., Barton, L. A., Chen, Y. G., & Ren, J. (2015). Mitochondrial aldehyde dehydrogenase in myocardial ischemia-reperfusion injury: From bench to bedside. Acta Physcologica Sinica, 67(6), 535–544. https://doi.org/10.1007/978-981-13-6260-6_6

    Article  CAS  Google Scholar 

  67. Jiang, W. B., Zhao, W., Chen, H., Wu, Y. Y., Wang, Y., Fu, G. S., & Yang, X. J. (2018). Baicalin protects H9c2 cardiomyocytes against hypoxia/reoxygenation-induced apoptosis and oxidative stress through activation of mitochondrial aldehyde dehydrogenase 2. Clinical and Experimental Pharmacology and Physiology, 45(3), 303–311. https://doi.org/10.1111/1440-1681.12876

    Article  CAS  PubMed  Google Scholar 

  68. Wang, Y., Wang, Y., Wang, X., & Hu, P. (2018). Tilianin-loaded reactive oxygen species-scavenging nano-micelles protect H9c2 cardiomyocyte against hypoxia/reoxygenation-induced injury. Journal of Cardiovascular Pharmacology, 72(1), 32–39. https://doi.org/10.1097/FJC.0000000000000587

    Article  CAS  PubMed  Google Scholar 

  69. Chen, S., Yang, B., Xu, Y., Rong, Y., & Qiu, Y. (2018). Protection of Luteolin-7-O-glucoside against apoptosis induced by hypoxia/reoxygenation through the MAPK pathways in H9c2 cells. Molecular Medicine Reports, 17(5), 7156–7162. https://doi.org/10.3892/mmr.2018.8774

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Liu, Z., Yang, L., Huang, J., Xu, P., Zhang, Z., Yin, D., Liu, J., He, H., & He, M. (2018). Luteoloside attenuates anoxia/reoxygenation-induced cardiomyocytes injury via mitochondrial pathway mediated by 14–3-3η protein. Phytotherapy Research, 32(6), 1126–1134. https://doi.org/10.1002/ptr.6053

    Article  CAS  PubMed  Google Scholar 

  71. Xue, W., Wang, X., Tang, H., Sun, F., Zhu, H., Huang, D., & Dong, L. (2020). Vitexin attenuates myocardial ischemia/reperfusion injury in rats by regulating mitochondrial dysfunction induced by mitochondrial dynamics imbalance. Biomedicine & Pharmacotherapy, 124, 109849. https://doi.org/10.1016/j.biopha.2020.109849

    Article  CAS  Google Scholar 

  72. Parra, V., Eisner, V., Chiong, M., Criollo, A., Moraga, F., Garcia, A., Härtel, S., Jaimovich, E., Zorzano, A., Hidalgo, C., & Lavandero, S. (2018). Changes in mitochondrial dynamics during ceramide-induced cardiomyocyte early apoptosis. Cardiovascular Research, 77(2), 387–397. https://doi.org/10.1093/cvr/cvm029

    Article  CAS  Google Scholar 

  73. Herrero, M., Plaza, M., Cifuentes, A., & Ibáñez, E. (2012). Extraction techniques for the determination of phenolic compounds in food. Intech Open. https://doi.org/10.5772/intechopen.84705

    Article  Google Scholar 

  74. Huang, L., He, H., Liu, Z., Liu, D., Yin, D., & He, M. (2016). Protective effects of isorhamnetin on cardiomyocytes against anoxia/reoxygenation-induced injury is mediated by SIRT1. Journal of Cardiovascular Pharmacology, 67(6), 526–537. https://doi.org/10.1097/FJC.0000000000000376

    Article  CAS  PubMed  Google Scholar 

  75. Zhao, T. T., Yang, T. L., Gong, L., & Wu, P. (2018). Isorhamnetin protects against hypoxia/reoxygenation-induced injure by attenuating apoptosis and oxidative stress in H9c2 cardiomyocytes. Gene, 666, 92–99. https://doi.org/10.1016/j.gene.2018.05.009

    Article  CAS  PubMed  Google Scholar 

  76. Wang, M., Sun, G. B., Du, Y. Y., Tian, Y., Liao, P., Liu, X. S., Ye, J. X., & Sun, X. B. (2017). Myricitrin protects cardiomyocytes from hypoxia/reoxygenation injury: Involvement of heat shock protein 90. Frontiers in Pharmacology, 8, 353. https://doi.org/10.3389/fphar.2017.00353

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Xiao, R., Xiang, A. L., Pang, H. B., & Liu, K. Q. (2017). Hyperoside protects against hypoxia/reoxygenation induced injury in cardiomyocytes by suppressing the Bnip3 expression. Gene, 629, 86–91. https://doi.org/10.1016/j.gene.2017.07.063

    Article  CAS  PubMed  Google Scholar 

  78. Cao, H., Xu, H., Zhu, G., & Liu, S. (2017). Isoquercetin ameliorated hypoxia/reoxygenation-induced H9C2 cardiomyocyte apoptosis via a mitochondrial-dependent pathway. Biomedicine & Pharmacotherapy, 95, 938–943. https://doi.org/10.1016/j.biopha.2017.08.128

    Article  CAS  Google Scholar 

  79. Liu, S., Wu, N., Miao, J., Huang, Z., Li, X., Jia, P., Guo, Y., & Jia, D. (2018). Protective effect of morin on myocardial ischemia-reperfusion injury in rats. International Journal of Molecular Medicine, 42(3), 1379–1390. https://doi.org/10.3892/ijmm.2018.3743

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Lozano, O., Lázaro-Alfaro, A., Silva-Platas, C., Oropeza-Almazán, Y., Torres-Quintanilla, A., Bernal-Ramírez, J., Alves-Figueiredo, H., & García-Rivas, G. (2019). Nanoencapsulated quercetin improves cardioprotection during hypoxia-reoxygenation injury through preservation of mitochondrial function. Oxidative Medicine and Cellular Longevity, 2019, 7683051. https://doi.org/10.1155/2019/7683051

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Yang, H., Wang, C., Zhang, L., Lv, J., & Ni, H. (2019). Rutin alleviates hypoxia/reoxygenation-induced injury in myocardial cells by upregulating SIRT1 expression. Chemico Biological Interactions, 297, 44–49. https://doi.org/10.1016/j.cbi.2018.10.016

    Article  CAS  PubMed  Google Scholar 

  82. Huang, J., & Qi, Z. (2020). MiR-21 mediates the protection of kaempferol against hypoxia/reoxygenation-induced cardiomyocyte injury via promoting Notch1/PTEN/AKT signalling pathway. PLoS ONE, 15(11), e0241007. https://doi.org/10.1371/journal.pone.0241007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Rodius, S., de Klein, N., Jeanty, C., Sánchez-Iranzo, H., Crespo, I., Ibberson, M., Xenarios, I., Dittmar, G., Mercader, N., Niclou, S. P., & Azuaje, F. (2020). Fisetin protects against cardiac cell death through reduction of ROS production and caspases activity. Science and Reports, 10(1), 1–12. https://doi.org/10.1038/s41598-020-59894-4

    Article  CAS  Google Scholar 

  84. Raman, G., Avendano, E. E., Chen, S., Wang, J., Matson, J., Gayer, B., Novotny, J. A., & Cassidy, A. (2019). Dietary intakes of flavan-3-ols and cardiometabolic health: Systematic review and meta-analysis of randomised trials and prospective cohort studies. American Journal of Clinical Nutrition, 110(5), 1067–1078. https://doi.org/10.1093/ajcn/nqz178

    Article  Google Scholar 

  85. Liu, S., Ai, Q., Feng, K., Li, Y., & Liu, X. (2016). The cardioprotective effect of dihydromyricetin prevents ischemia–reperfusion-induced apoptosis in vivo and in vitro via the PI3K/Akt and HIF-1α signalling pathways. Apoptosis, 21(12), 1366–1385. https://doi.org/10.1007/s10495-016-1306-6

    Article  CAS  PubMed  Google Scholar 

  86. Wu, Y., Xia, Z. Y., Zhao, B., Leng, Y., Dou, J., Meng, Q. T., Lei, S. Q., Chen, Z. Z., & Zhu, J. (2017). Epigallocatechin-3-gallate attenuates myocardial injury induced by ischemia/reperfusion in diabetic rats and in H9c2 cells under hyperglycemic conditions. International Journal of Molecular Medicine, 40(2), 389–399. https://doi.org/10.3892/ijmm.2017.3014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Zhang, C., Liao, P., Liang, R., Zheng, X., & Jian, J. (2019). Epigallocatechin gallate prevents mitochondrial impairment and cell apoptosis by regulating miR-30a/p53 axis. Phytomedicine, 61, 152845. https://doi.org/10.1016/j.phymed.2019.152845

    Article  CAS  PubMed  Google Scholar 

  88. Kozlowska, A., & Szostak-Wegierek, D. (2014). Flavonoids-food sources and health benefits. Roczniki Państwowego Zakładu Higieny, 65(2), 79.

    PubMed  Google Scholar 

  89. He, S., Wang, X., Zhong, Y., Tang, L., Zhang, Y., Ling, Y., Tan, Z., Yang, P., & Chen, A. (2017). Hesperetin post-treatment prevents rat cardiomyocytes from hypoxia/reoxygenation injury in vitro via activating PI3K/Akt signalling pathway. Biomedicine & Pharmacotherapy, 91, 1106–1112. https://doi.org/10.1016/j.biopha.2017.05.003

    Article  CAS  Google Scholar 

  90. Tang, J.-Y., Ping, J., Qing, H., Lu, L.-H., Ma, J.-P., Gao, W.-L., Bai, H.-P., & Yang, J. (2017). Naringenin ameliorates hypoxia/reoxygenation-induced endoplasmic reticulum stress-mediated apoptosis in H9c2 myocardial cells: involvement in ATF6, IRE1α and PERK signalling activation. Molecular Cellular and Biochemistry, 2017(424), 111–122.

    Article  Google Scholar 

  91. Xie, Y., Ji, R., & Han, M. (2019). Eriodictyol protects H9c2 cardiomyocytes against the injury induced by hypoxia/reoxygenation by improving the dysfunction of mitochondria. Experimental and Therapeutic Medicine, 17(1), 551–557. https://doi.org/10.3892/etm.2018.6918

    Article  CAS  PubMed  Google Scholar 

  92. Thrane, M., Paulsen, P. V., Orcutt, M. W., & Krieger, T. M. (2017). Sustainable protein sources: Soy protein: Impacts, production, and applications. CAmbridge: Academic Press.

    Google Scholar 

  93. Ma, Y., Gai, Y., Yan, J., Jian, J., & Zhang, Y. (2016). Puerarin attenuates anoxia/reoxygenation injury through enhancing Bcl-2 associated athanogene 3 expression, a modulator of apoptosis and autophagy. International Journal of Clinical and Experimental Medicine Research, 22, 977. https://doi.org/10.12659/MSM.897379

    Article  CAS  Google Scholar 

  94. Tang, H., Song, X., Ling, Y., Wang, X., Yang, P., Luo, T., & Chen, A. (2017). Puerarin attenuates myocardial hypoxia/reoxygenation injury by inhibiting autophagy via the Akt signalling pathway. Molecular Medicine Reports, 15(6), 3747–3754. https://doi.org/10.3892/mmr.2017.6424

    Article  CAS  PubMed  Google Scholar 

  95. Khoo, H. E., Azlan, A., Tang, S. T., & Lim, S. M. (2017). Anthocyanidins and anthocyanins: Colored pigments as food, pharmaceutical ingredients, and the potential health benefits. Food & Nutrition Research, 61(1), 1361779. https://doi.org/10.1080/16546628.2017.1361779

    Article  CAS  Google Scholar 

  96. Wang, X., Jia, D., Zhang, J., & Wang, W. (2017). Grape seed proanthocyanidins protect cardiomyocytes against hypoxia/reoxygenation injury by attenuating endoplasmic reticulum stress through PERK/eIF2α pathway. Molecular Medicine Reports, 16(6), 9189–9196. https://doi.org/10.3892/mmr.2017.7756

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the Herbal Research Grant Scheme by the Malaysian Ministry of Agriculture (Grant code304.PPSK.6150169.K123) and S.S.A received funding from GRA-ASSIST USM 2020/2021. Thank you to all of the peer reviewers and editors for their opinions and suggestions.

Funding

This work was supported by the Herbal Research Grant Scheme by the Malaysian Ministry of Agriculture (Grant code304.PPSK.6150169.K123) and S.S.A received funding from GRA-ASSIST USM 2020/2021.

Author information

Authors and Affiliations

  1. Programme of Biomedicine, School of Health Sciences (PPSK), Universiti Sains Malaysia, Health Campus, 16150, Kubang Kerian, Kelantan, Malaysia

    Shafreena Shaukat Ali & Wan Amir Nizam Wan Ahmad

  2. Department of Physiology, School of Medical Sciences (PPSP), Universiti Sains Malaysia, Health Campus, 16150, Kubang Kerian, Kelantan, Malaysia

    Liza Noordin

  3. Department of Pharmacology, School of Medical Sciences (PPSP), Universiti Sains Malaysia, Health Campus, 16150, Kubang Kerian, Kelantan, Malaysia

    Ruzilawati Abu Bakar

  4. Programme of Biomedical Science, Faculty of Health Sciences, Center for Toxicology and Health Risk Studies (CORE), Universiti Kebangsaan Malaysia, 50300, Kuala Lumpur, Malaysia

    Satirah Zainalabidin

  5. Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, 56000, Kuala Lumpur, Malaysia

    Zakiah Jubri

Authors
  1. Shafreena Shaukat Ali
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Liza Noordin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ruzilawati Abu Bakar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Satirah Zainalabidin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zakiah Jubri
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wan Amir Nizam Wan Ahmad
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wan Amir Nizam Wan Ahmad.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Handling Editor: Y. Robert Li.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ali, S.S., Noordin, L., Bakar, R.A. et al. Current Updates on Potential Role of Flavonoids in Hypoxia/Reoxygenation Cardiac Injury Model. Cardiovasc Toxicol 21, 605–618 (2021). https://doi.org/10.1007/s12012-021-09666-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12012-021-09666-x

Keywords

Search

Navigation