Skip to main content

Baicalein protects isoproterenol induced myocardial ischemic injury in male Wistar rats by mitigating oxidative stress and inflammation

Inflammation Research volume 65, pages 613–622 (2016)Cite this article

Abstract

Objective

The aim of the present study was to investigate the cardioprotective effects of baicalein, main bioactive constituent from roots of Scutellaria baicalensis and Scutellaria lateriflora, on isoproterenol (ISO) induced acute myocardial infarction model in rats and to explore the underlying mechanisms.

Method

Rats were treated with baicalein (50 mg/kg and 100 mg/kg) orally for 14 days and on 13th and 14th day, myocardial injury was induced by ISO injection (100 mg/kg, subcutaneous) at an interval of 24 h.

Result

Our study showed that ISO administration resulted in significant elevations in the levels of cardiac injury biomarkers such as cardiac troponin I, creatine kinase-MB, AST and ALT. Concentrations of reactive nitrogen species and reactive oxygen species in the heart tissue increased significantly while antioxidant enzymes level declined. The levels of tissue pro-inflammatory cytokines tumor necrosis factor-α and interleukin-6 were significantly increased after ISO administration. Pretreatment with baicalein significantly reversed these alterations induced by ISO administration. Exploration of the underlying mechanisms of protective effect of baicalein pretreatment revealed that it repressed the expression of nuclear factor kappa B and restored the ISO induced elevation of pro-inflammatory cytokines, oxidative and nitrosative stress. We found that baicalein pretreatment enhanced the level of antioxidant defense enzymes like SOD, catalase and GSH. Furthermore, the present study also demonstrated cardioprotective effects of baicalein by the histopathological findings.

Conclusion

Taken together, our findings demonstrated that baicalein pretreatment might have a potential benefit in prevention and terminating ischemic heart diseases like myocardial infarction.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Abbreviations

ISO:

Isoproterenol

MI:

Myocardial infarction

NF-κB:

Nuclear factor kappa-light-chain enhancer of activated B cells

TNF-α:

Tumor necrosis factor α

IL-6:

Interleukin 6

IL-10:

Interleukin 10

SOD:

Superoxide dismutase

MDA:

Malondialdehyde

GSH:

Glutathione

References

  1. Alla F, Zannad F, Filippatos G. Epidemiology of acute heart failure syndromes. Heart Fail Rev. 2007;12(2):91–5.

    Article  PubMed  Google Scholar 

  2. Aronow WS. Epidemiology, pathophysiology, prognosis, and treatment of systolic and diastolic heart failure. Cardiol Rev. 2006;14(3):108–24.

    Article  PubMed  Google Scholar 

  3. Patel V, Upaganlawar A, Zalawadia R, Balaraman R. Cardioprotective effect of melatonin against isoproterenol induced myocardial infarction in rats: a biochemical, electrocardiographic and histoarchitectural evaluation. Eur J Pharmacol. 2010;644(1–3):160–8.

    CAS  Article  PubMed  Google Scholar 

  4. Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD, et al. Third universal definition of myocardial infarction. J Am CollCardiol. 2012;60(16):1581–98.

    Article  Google Scholar 

  5. Sawyer DB, Siwik DA, Xiao L, Pimentel DR, Singh K, Colucci WS. Role of oxidative stress in myocardial hypertrophy and failure. J Mol Cell Cardiol. 2002;34(4):379–88.

    CAS  Article  PubMed  Google Scholar 

  6. Bagatini MD, Martins CC, Battisti V, Gasparetto D, Da Rosa CS, Spanevello RM, et al. Oxidative stress versus antioxidant defenses in patients with acute myocardial infarction. Heart Vessels. 2011;26(1):55–63.

    Article  PubMed  Google Scholar 

  7. Wang S, Tian S, Yang F, Yang H, Yang X, Du G. Cardioprotective effect of salvianolic acid A on isoproterenol-induced myocardial infarction in rats. Eur J Pharmacol. 2009;615(1–3):125–32.

    CAS  Article  PubMed  Google Scholar 

  8. Rona G. Catecholamine cardiotoxicity. J Mol Cell Cardiol. 1985;17(4):291–306.

    CAS  Article  PubMed  Google Scholar 

  9. Rona G, Chappel CI, Balazs T, Gaudry R. An infarct-like myocardial lesion and other toxic manifestations produced by isoproterenol in the rat. AMA Arch Pathol. 1959;67(4):443–55.

    CAS  PubMed  Google Scholar 

  10. Yates JC, Beamish RE, Dhalla NS. Ventricular dysfunction and necrosis produced by adrenochrome metabolite of epinephrine: relation to pathogenesis of catecholamine cardiomyopathy. Am Heart J. 1981;102(2):210–21.

    CAS  Article  PubMed  Google Scholar 

  11. Brooks WW, Conrad CH. Isoproterenol-induced myocardial injury and diastolic dysfunction in mice: structural and functional correlates. Comp Med. 2009;59(4):339–43.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Rajadurai M, Prince PSM. Preventive effect of naringin on lipid peroxides and antioxidants in isoproterenol-induced cardiotoxicity in Wistar rats: biochemical and histopathological evidences. Toxicology. 2006;228(2):259–68.

    CAS  Article  PubMed  Google Scholar 

  13. Prince PSM, Rajakumar S, Dhanasekar K. Protective effects of vanillic acid on electrocardiogram, lipid peroxidation, antioxidants, proinflammatory markers and histopathology in isoproterenol induced cardiotoxic rats. Eur J Pharmacol. 2011;668(1–2):233–40.

    CAS  Article  Google Scholar 

  14. Zhou R, Xu Q, Zheng P, Yan L, Zheng J, Dai G. Cardioprotective effect of fluvastatin on isoproterenol-induced myocardial infarction in rat. Eur J Pharmacol. 2008;586(1–3):244–50.

    CAS  Article  PubMed  Google Scholar 

  15. Mu X, He G, Cheng Y, Li X, Xu B, Du G. Baicalein exerts neuroprotective effects in 6-hydroxydopamine-induced experimental parkinsonism in vivo and in vitro. Pharmacol Biochem Behav. 2009;92(4):642–8.

    CAS  Article  PubMed  Google Scholar 

  16. Wang CZ, Li XL, Wang QF, Mehendale SR, Yuan CS. Selective fraction of Scutellaria baicalensis and its chemopreventive effects on MCF-7 human breast cancer cells. Phytomedicine. 2010;17(1):63–8.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  17. Shao ZH, VandenHoek TL, Qin Y, Becker LB, Schumacker PT, Li CQ, et al. Am J Physiol Heart Circ Physiol. 2002;282(3):H999–1006.

    CAS  Article  PubMed  Google Scholar 

  18. Woo AY, Cheng CH, Waye MM. Baicalein protects rat cardiomyocytes from hypoxia/reoxygenation damage via a prooxidant mechanism. Cardiovasc Res. 2005;65(1):244–53.

    CAS  Article  PubMed  Google Scholar 

  19. Gabrielska J, Oszmiański J, Zyłka R, Komorowska M. Antioxidant activity of flavones from Scutellaria baicalensisin lecithin liposomes. Z Naturforsch C. 1997;52(11–12):817–23.

    CAS  PubMed  Google Scholar 

  20. De Carvalho RS, Duarte FS, de Lima TC. Involvement of GABAergic non-benzodiazepine sites in the anxiolytic-like and sedative effects of the flavonoid baicalein in mice. Behav Brain Res. 2011;221(1):75–82.

    Article  PubMed  Google Scholar 

  21. Xiong Z, Jiang B, Wu PF, Tian J, Shi LL, Gu J, et al. Antidepressant effects of a plant-derived flavonoid baicalein involving extracellular signal-regulated kinases cascade. Biol Pharm Bull. 2011;34(2):253–9.

    CAS  Article  PubMed  Google Scholar 

  22. Hsieh CJ, Hall K, Ha T, Li C, Krishnaswamy G, Chi DS. Baicalein inhibits IL-1beta- and TNF-alpha-induced inflammatory cytokine production from human mast cells via regulation of the NF-kappaB pathway. Clin Mol Allergy. 2007;26(5):5.

    Article  Google Scholar 

  23. Deschamps JD, Kenyon VA, Holman TR. Baicalein is a potent in vitro inhibitor against both reticulocyte 15-human and platelet 12-human lipoxygenases. Bioorg Med Chem. 2006;14(12):4295–301.

    CAS  Article  PubMed  Google Scholar 

  24. Lin CC, Shieh DE. The anti-inflammatory activity of Scutellariarivularis extracts and its active components, baicalin, baicalein and wogonin. Am J Chin Med. 1996;24(1):31–6.

    CAS  Article  PubMed  Google Scholar 

  25. Panda VS, Naik SR. Cardioprotective activity of Ginkgo bilobaphytosomes in isoproterenol induced myocardial necrosis in rats: a biochemical and histoarchitectural evaluation. Exp Toxicol Pathol. 2008;60(4–5):397–404.

    Article  PubMed  Google Scholar 

  26. Budhani MK, Dahiya V, Kasala ER, Bodduluru LN, Sharma D, Lahkar M, Kumar V. Animal models of myocardial infarction: mainstay in clinical translation. Regul Toxicol Pharmacol. 2016;. doi:10.1016/j.yrtph.2016.03.005.

    Google Scholar 

  27. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95(2):351–8.

    CAS  Article  PubMed  Google Scholar 

  28. Sinha AK. Colorimetric assay of catalase. Anal Biochem. 1972;47(2):389–94.

    CAS  Article  PubMed  Google Scholar 

  29. Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959;82(1):70–7.

    CAS  Article  PubMed  Google Scholar 

  30. Fischer AH, Jacobson KA, Rose J, Zeller R. Hematoxylin and eosin staining of tissue and cell sections. Cold Spring Harb Protoc. 2008. doi:10.1101/pdb.prot4986.

    Google Scholar 

  31. Deng X-Y, Chen J-J, Li H-Y, Ma Z-Q, Ma S-P, Fu Q. Cardioprotective effects of timosaponin B II from Anemarrhenae asphodeloides Bge on isoproterenol-induced myocardial infarction in rats. Chem Biol Int. 2015;240:22–8.

    CAS  Article  Google Scholar 

  32. Kasala ER, Bodduluru LN, Barua CC, Madana RM, Dahiya V, Budhani MK et al. Chemopreventive effect of chrysin, a dietary flavone against benzo (a) pyrene induced lung carcinogenesis in Swiss albino mice. Pharmacol Rep. doi:10.1016/j.pharep.2015.08.014.

  33. Booth EA, Lucchesi BR. Estrogen-mediated protection in myocardial ischemia-reperfusion injury. Cardiovasc Toxicol. 2008;8(3):101–13.

    CAS  Article  PubMed  Google Scholar 

  34. Deschamps AM, Murphy E, Sun J. Estrogen receptor activation and cardioprotection in ischemia reperfusion injury. Trends Cardiovasc Med. 2011;20(3):73–8.

    Article  Google Scholar 

  35. Willerson JT, Ridker PM. Inflammation as a cardiovascular risk factor. Circulation. 2004;109(21 suppl 1):II-2-10.

    Google Scholar 

  36. Gasparyan AY. Cardiovascular risk and inflammation: pathophysiological mechanisms, drug design, and targets. Curr Pharm Des. 2012;18(11):1447–9.

    CAS  Article  PubMed  Google Scholar 

  37. Karin M, Delhase M. The I kappa B kinase (IKK) and NF-kappa B: key elements of proinflammatory signalling. Semin Immunol. 2000;12(1):85–98.

    CAS  Article  PubMed  Google Scholar 

  38. Frangogiannis NG, Smith CW, Entman ML. The inflammatory response in myocardial infarction. Cardiovasc Res. 2002;53(1):31–47.

    CAS  Article  PubMed  Google Scholar 

  39. Ruparelia N, Digby JE, Andrew J, Debra J, et al. Myocardial infarction causes inflammation and leukocyte recruitment ar remote sites in the myocardium and in the renal glomerulus. Inflamm Res. 2013;62(5):515–25.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  40. Zheng W, Huang LZ, Zhao L, Wang B, Xu HB, Wang GY, et al. Superoxide dismutase activity and malondialdehyde level in plasma and morphological evaluation of acute severe hemorrhagic shock in rats. Am J Emerg Med. 2008;26(1):54–8.

    Article  PubMed  Google Scholar 

Download references

Acknowledgement

This work was supported by National Institute of Pharmaceutical Education and Research-Guwahati, under the aegis of Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Government of India. The authors would like to thank Professor Dr. Ena Dowerah Department of Pathology, Gauhati Medical College, Guwahati, Assam, for evaluation of histopathology slides.

Author information

Author notes

  1. Mukesh Kumar

    Present address: Department of Pharmaceutics, Indian Institute of Technology, Banaras Hindu University, Varanasi, UP, 221 005, India

Authors and Affiliations

  1. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam, 781032, India

    Mukesh Kumar, Eshvendar Reddy Kasala, Lakshmi Narendra Bodduluru, Vicky Dahiya & Mangala Lahkar

  2. Department of Pharmacology, Gauhati Medical College, Guwahati, Assam, 781032, India

    Mangala Lahkar

Authors
  1. Mukesh Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eshvendar Reddy Kasala
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lakshmi Narendra Bodduluru
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vicky Dahiya
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mangala Lahkar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mukesh Kumar.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Additional information

Responsible Editor: John Di Battista.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Kumar, M., Kasala, E.R., Bodduluru, L.N. et al. Baicalein protects isoproterenol induced myocardial ischemic injury in male Wistar rats by mitigating oxidative stress and inflammation. Inflamm. Res. 65, 613–622 (2016). https://doi.org/10.1007/s00011-016-0944-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00011-016-0944-z

Keywords

  • Isoproterenol
  • Baicalein
  • Myocardial infarction
  • Reactive oxygen species
  • Inflammatory cytokines