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Cardiovascular Toxicology

, Volume 19, Issue 1, pp 72–81 | Cite as

Anti-fibrotic Actions of Roselle Extract in Rat Model of Myocardial Infarction

  • Shafreena Shaukat Ali
  • Siti Fatimah Azaharah Mohamed
  • Nur Hafiqah Rozalei
  • Yap Wei Boon
  • Satirah ZainalabidinEmail author
Article

Abstract

Heart failure-associated morbidity and mortality is largely attributable to extensive and unregulated cardiac remodelling. Roselle (Hibiscus sabdariffa) calyces are enriched with natural polyphenols known for antioxidant and anti-hypertensive effects, yet its effects on early cardiac remodelling in post myocardial infarction (MI) setting are still unclear. Thus, the aim of this study was to investigate the actions of roselle extract on cardiac remodelling in rat model of MI. Male Wistar rats (200–300 g) were randomly allotted into three groups: Control, MI, and MI + Roselle. MI was induced with isoprenaline (ISO) (85 mg/kg, s.c) for two consecutive days followed by roselle treatment (100 mg/kg, orally) for 7 days. Isoprenaline administration showed changes in heart weight to body weight (HW/BW) ratio. MI was especially evident by the elevated cardiac injury marker, troponin-T, and histological observation. Upregulation of plasma levels and cardiac gene expression levels of inflammatory cytokines such as interleukin (IL)-6 and IL-10 was seen in MI rats. A relatively high percentage of fibrosis was observed in rat heart tissues with over-expression of collagen (Col)-1 and Col-3 genes following isoprenaline-induced MI. On top of that, cardiomyocyte areas were larger in heart tissues of MI rats with upregulation of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) gene expression, indicating cardiac hypertrophy. Interestingly, roselle supplementation attenuated elevation of plasma troponin-T, IL-6, IL10, and gene expression level of IL-10. Furthermore, reduction of cardiac fibrosis and hypertrophy were observed. In conclusion, roselle treatment was able to limit early cardiac remodelling in MI rat model by alleviating inflammation, fibrosis, and hypertrophy; hence, the potential application of roselle in early adjunctive treatment to prevent heart failure.

Keywords

Roselle Isoprenaline Fibrosis Inflammation Hypertrophy Cardiac remodelling 

Notes

Acknowledgements

This project was funded by Malaysian Toray Science Foundation (MTSF) under the Grant Code NN-2016-082 and Geran Universiti Penyelidikan under Grant Code GUP-2017-018.

Compliance with Ethical Standards

Conflict of interest

The authors declare that there is no conflict of interest regarding the publication of this paper.

References

  1. 1.
    Khorrami, A., Hammami, M., Garjani, M., Maleki-Dizaji, N., & Garjani, A. (2014). Tacrolimus ameliorates functional disturbances and oxidative stress in isoproterenol-induced myocardial infarction. DARU Journal of Pharmaceutical Sciences, 22(1), 68.Google Scholar
  2. 2.
    Department of Statistics Malaysia. (2017). Press release: Statistics on causes of death, Malaysia. Retrieved December 29, 2017 from, https://www.dosm.gov.my.
  3. 3.
    Lopez, A. D., & Murray, C. C. (1998). The global burden of disease, 1990–2020. Nature Medicine, 4(11), 1241.Google Scholar
  4. 4.
    Aronow, W. S. (2006). Epidemiology, pathophysiology, prognosis, and treatment of systolic and diastolic heart failure. Cardiology in Review, 14(3), 108–124.Google Scholar
  5. 5.
    Ulla, A., Mohamed, M. K., Sikder, B., Rahman, A. T., Sumi, F. A., Hossain, M., et al. (2017). Coenzyme Q10 prevents oxidative stress and fibrosis in isoprenaline induced cardiac remodeling in aged rats. BMC Pharmacology and Toxicology, 18(1), 29.Google Scholar
  6. 6.
    Hori, M., & Nishida, K. (2008). Oxidative stress and left ventricular remodelling after myocardial infarction. Cardiovascular Research, 81(3), 457–464.Google Scholar
  7. 7.
    Minicucci, M. F., Azevedo, P. S., Polegato, B. F., Paiva, S. A., & Zornoff, L. A. (2011). Heart failure after myocardial infarction: Clinical implications and treatment. Clinical Cardiology, 34(7), 410–414.Google Scholar
  8. 8.
    Suthahar, N., Meijers, W. C., Silljé, H. H., & de Boer, R. A. (2017). From inflammation to fibrosis—Molecular and cellular mechanisms of myocardial tissue remodelling and perspectives on differential treatment opportunities. Current Heart Failure Reports, 14(4), 235–250.Google Scholar
  9. 9.
    Bonvini, R. F., Hendiri, T., & Camenzind, E. (2005). Inflammatory response post-myocardial infarction and reperfusion: A new therapeutic target? European Heart Journal Supplements, 7(suppl_I), I27–I36.Google Scholar
  10. 10.
    Azevedo, P. S., Polegato, B. F., Minicucci, M. F., Paiva, S. A., & Zornoff, L. A. (2016). Cardiac remodeling: Concepts, clinical impact, pathophysiological mechanisms and pharmacologic treatment. Arquivos Brasileiros de Cardiologia, 106(1), 62–69.Google Scholar
  11. 11.
    Zaafan, M. A., Zaki, H. F., El-Brairy, A. I., & Kenawy, S. A. (2013). Protective effects of atorvastatin and quercetin on isoprenaline-induced myocardial infarction in rats. Bulletin of Faculty of Pharmacy, Cairo University, 51(1), 35–41.Google Scholar
  12. 12.
    Patel, V., Upaganlawar, A., Zalawadia, R., & Balaraman, R. (2010). Cardioprotective effect of melatonin against isoproterenol induced myocardial infarction in rats: A biochemical, electrocardiographic and histoarchitectural evaluation. European Journal of Pharmacology, 644(1), 160–168.Google Scholar
  13. 13.
    Sözmen, M., Devrim, A. K., Kabak, Y. B., Devrim, T., & Sudagidan, M. (2017). The effects of periostin in a rat model of isoproterenol: Mediated Cardiotoxicity. Cardiovascular Toxicology, 18(2), 142–160.Google Scholar
  14. 14.
    Akila, P., & Vennila, L. (2016). Chlorogenic acid a dietary polyphenol attenuates isoproterenol induced myocardial oxidative stress in rat myocardium: An in vivo study. Biomedicine & Pharmacotherapy, 84, 208–214.Google Scholar
  15. 15.
    Si, L. Y. N., Kamisah, Y., Ramalingam, A., Lim, Y. C., Budin, S. B., & Zainalabidin, S. (2017). Roselle supplementation prevents nicotine-induced vascular endothelial dysfunction and remodelling in rats. Applied Physiology, Nutrition, and Metabolism, 42(7), 765–772.Google Scholar
  16. 16.
    Rona, G., Chappel, C., Balazs, T., & Gaudry, R. (1959). An infarct-like myocardial lesion and other toxic manifestations produced by isoproterenol in the rat. AMA Archives of Pathology, 67(4), 443–455.Google Scholar
  17. 17.
    Siddiqui, M. A., Ahmad, U., Khan, A. A., Ahmad, M., Badruddeen, Khalis, M., & Akhtar, J. (2016). Isoprenaline: A tool for inducing myocardial infarction in experimental animals. International Journal of Pharmacy, 6(2), 138–144.Google Scholar
  18. 18.
    Panda, V. S., & Naik, S. R. (2008). Cardioprotective activity of Ginkgo biloba phytosomes in isoproterenol-induced myocardial necrosis in rats: A biochemical and histoarchitectural evaluation. Experimental and Toxicologic Pathology, 60(4), 397–404.Google Scholar
  19. 19.
    Prince, P. S. M., Dhanasekar, K., & Rajakumar, S. (2011). Preventive effects of vanillic acid on lipids, bax, bcl-2 and myocardial infarct size on isoproterenol-induced myocardial infarcted rats: A biochemical and in vitro study. Cardiovascular Toxicology, 11(1), 58–66.Google Scholar
  20. 20.
    Si, L. Y. N., Ali, S. A. M., Latip, J., Fauzi, N. M., Budin, S. B., & Zainalabidin, S. (2017). Roselle is cardioprotective in diet-induced obesity rat model with myocardial infarction. Life Sciences, 191, 157–165.Google Scholar
  21. 21.
    Zainalabidin, S., Shahidin, S. N. F. S. N., & Budin, S. B. (2016). Hibiscus sabdariffa Linn. (Roselle) protects against nicotine-induced heart damage in rats. Sains Malaysiana, 45(2), 207–214.Google Scholar
  22. 22.
    Ramalingam, A., Budin, S. B., Lim, Y. C., Si, Y.-N. L., & Zainalabidin, S. (2016). Dietary UKMR-1 roselle supplementation prevents nicotine-induced cardiac injury by inhibiting myocardial oxidative stress. Sains Malaysiana, 45(7), 1131–1137.Google Scholar
  23. 23.
    Mohamed, J., Shing, S. W., Idris, M. H. M., Budin, S. B., & Zainalabidin, S. (2013). The protective effect of aqueous extracts of roselle (Hibiscus sabdariffa L. UKMR-2) against red blood cell membrane oxidative stress in rats with streptozotocin-induced diabetes. Clinics, 68(10), 1358–1363.Google Scholar
  24. 24.
    Wróblewski, F., & Ladue, J. S. (1955). Lactic dehydrogenase activity in blood. Proceedings of the Society for Experimental Biology and Medicine, 90(1), 210–213.Google Scholar
  25. 25.
    Curley, D., Plaza, B. L., Shah, A. M., & Botnar, R. M. (2018). Molecular imaging of cardiac remodelling after myocardial infarction. Basic Research in Cardiology, 113(2), 10.Google Scholar
  26. 26.
    Sutton, M. G. S. J., & Sharpe, N. (2000). Left ventricular remodeling after myocardial infarction. Circulation, 101(25), 2981–2988.Google Scholar
  27. 27.
    Upaganlawar, A., Gandhi, H., & Balaraman, R. (2011). Isoproterenol induced myocardial infarction: Protective role of natural products. Journal of Pharmacology and Toxicology, 6(1), 1–17.Google Scholar
  28. 28.
    Moradi-Arzeloo, M., Farshid, A. A., Tamaddonfard, E., & Asri-Rezaei, S. (Eds.). (2016). Effects of histidine and vitamin C on isoproterenol-induced acute myocardial infarction in rats. Urmia, Iran: Veterinary Research Forum, Faculty of Veterinary Medicine, Urmia University.Google Scholar
  29. 29.
    Gayathri, V., Ananthi, S., Chandronitha, C., Ramakrishnan, G., Sundaram, R. L., & Vasanthi, H. R. (2011). Cardioprotective effect of Nerium oleander flower against isoproterenol-induced myocardial oxidative stress in experimental rats. Journal of Cardiovascular Pharmacology and Therapeutics, 16(1), 96–104.Google Scholar
  30. 30.
    Mnafgui, K., Hajji, R., Derbali, F., Khlif, I., Kraiem, F., Ellefi, H., et al. (2016). Protective effect of hydroxytyrosol against cardiac remodeling after isoproterenol-induced myocardial infarction in rat. Cardiovascular Toxicology, 16(2), 147–155.Google Scholar
  31. 31.
    Judd, J. T., & Wexler, B. C. (1974). Myocardial glycoprotein changes with isoproterenol-induced necrosis and repair in the rat. American Journal of Physiology–Legacy Content, 226(3), 597–602.Google Scholar
  32. 32.
    Laine, G. A., & Allen, S. J. (1991). Left ventricular myocardial edema. Lymph flow, interstitial fibrosis, and cardiac function. Circulation Research, 68(6), 1713–1721.Google Scholar
  33. 33.
    Licka, M., Zimmermann, R., Zehelein, J., Dengler, T., Katus, H., & Kübler, W. (2002). Troponin T concentrations 72 hours after myocardial infarction as a serological estimate of infarct size. Heart, 87(6), 520–524.Google Scholar
  34. 34.
    Hasić, S., Jadrić, R., Kiseljaković, E., Mornjaković, Z., & Winterhalter-Jadrić, M. (2007). Troponin T and histological characteristics of rat myocardial infarction induced by isoproterenol. Bosnian Journal of Basic Medical Sciences, 7(3), 212.Google Scholar
  35. 35.
    Frangogiannis, N. G. (2014). The inflammatory response in myocardial injury, repair, and remodelling. Nature Reviews Cardiology, 11(5), 255.Google Scholar
  36. 36.
    Frangogiannis, N. G. (2018). Cell biological mechanisms in regulation of the post-infarction inflammatory response. Current Opinion in Physiology, 1, 7–13.Google Scholar
  37. 37.
    Nian, M., Lee, P., Khaper, N., & Liu, P. (2004). Inflammatory cytokines and postmyocardial infarction remodeling. Circulation Research, 94(12), 1543–1553.Google Scholar
  38. 38.
    Akasaka, Y., Morimoto, N., Ishikawa, Y., Fujita, K., Ito, K., Kimura-Matsumoto, M., et al. (2006). Myocardial apoptosis associated with the expression of proinflammatory cytokines during the course of myocardial infarction. Modern Pathology, 19(4), 588–598.Google Scholar
  39. 39.
    Patel, K., Duggan, S., Currid, C., Gallagher, W., McManus, R., Kelleher, D., et al. (2009). High sensitivity cytokine detection in acute coronary syndrome reveals up-regulation of interferon gamma and interleukin-10 post myocardial infarction. Clinical Immunology, 133(2), 251–256.Google Scholar
  40. 40.
    Ahmet, I., Spangler, E., Shukitt-Hale, B., Juhaszova, M., Sollott, S. J., Joseph, J. A., et al. (2009). Blueberry-enriched diet protects rat heart from ischemic damage. PLoS One, 4(6), e5954.Google Scholar
  41. 41.
    Davel, A. P. C., Fukuda, L. E., De Sá, L. L., Munhoz, C. D., Scavone, C., Sanz-Rosa, D., et al. (2008). Effects of isoproterenol treatment for 7 days on inflammatory mediators in the rat aorta. American Journal of Physiology-Heart and Circulatory Physiology, 295(1), H211–H219.Google Scholar
  42. 42.
    Weber, K. T., Janicki, J. S., Shroff, S. G., Pick, R., Chen, R. M., & Bashey, R. I. (1988). Collagen remodeling of the pressure-overloaded, hypertrophied nonhuman primate myocardium. Circulation Research, 62(4), 757–765.Google Scholar
  43. 43.
    Chen, Y.-F., Shibu, M. A., Fan, M.-J., Chen, M.-C., Viswanadha, V. P., Lin, Y.-L., et al. (2016). Purple rice anthocyanin extract protects cardiac function in STZ-induced diabetes rat hearts by inhibiting cardiac hypertrophy and fibrosis. The Journal of Nutritional Biochemistry, 31, 98–105.Google Scholar
  44. 44.
    Sohn, D. W., Bae, W. J., Kim, H. S., Kim, S. W., & Kim, S. W. (2014). The anti-inflammatory and antifibrosis effects of anthocyanin extracted from black soybean on a Peyronie disease rat model. Urology, 84(5), 1112–1116.Google Scholar
  45. 45.
    Srivastav, R. K., Siddiqui, H. H., Mahmood, T., & Ahsan, F. (2013). Evaluation of cardioprotective effect of silk cocoon (Abresham) on isoprenaline-induced myocardial infarction in rats. Avicenna Journal of Phytomedicine, 3(3), 216.Google Scholar
  46. 46.
    Zhang, Y., Xu, J., Long, Z., Wang, C., Wang, L., Sun, P., Li, P., & Wang, T. (2016). Hydrogen (H2) Inhibits isoproterenol-induced cardiac hypertrophy via antioxidative pathways. Frontiers in Pharmacology, 7, 392.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Shafreena Shaukat Ali
    • 1
  • Siti Fatimah Azaharah Mohamed
    • 1
  • Nur Hafiqah Rozalei
    • 1
  • Yap Wei Boon
    • 1
  • Satirah Zainalabidin
    • 1
    Email author
  1. 1.Biomedical Science, School of Diagnostic Sciences & Applied Health, Faculty of Health SciencesUniversiti Kebangsaan MalaysiaKuala LumpurMalaysia

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