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Mechanistic Clues in the Cardioprotective Effect of Terminalia Arjuna Bark Extract in Isoproterenol-Induced Chronic Heart Failure in Rats

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Abstract

The present study demonstrated prophylactic and therapeutic potential of Terminalia arjuna bark extract in isoproterenol (ISO)-induced chronic heart failure (CHF). Fifteen days after injection of ISO (85 mg/kg twice at an interval of 24 h, s.c), rats showed decline in maximal rate of rise and fall of left ventricular pressure (LV (dP/dt)max and LV (dP/dt)min), cardiac contractility index (LV (dP/dt)max/LVP), cardiac output and rise in LV end-diastolic pressure. CHF rats showed a significant increase in serum creatine kinase isoenzyme-MB (CK-MB) and malondialdehyde levels, as well as fall in the activities of superoxide dismutase, reduced glutathione. Altered lipid profile and increased level of cytokine tumour necrosis factor-α (TNF-α) along with histological changes in heart were also observed in CHF rats. T. arjuna bark extract (500 mg/kg, p.o) treatment prior and 15 days after ISO injection significantly attenuated cardiac dysfunction and myocardial injury in CHF rats. Cardioprotective action of T. arjuna was comparable to fluvastatin, a synthetic drug. The results suggest that T. arjuna bark extract has a significant prophylactic and therapeutic beneficial effect on protection of heart against ISO-induced CHF possibly through maintaining endogenous antioxidant enzyme activities, inhibiting lipid peroxidation and cytokine levels.

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References

  1. Lloyd-Jones, D. M., Larson, M. G., Leip, E. P., Beiser, A., D’Agostino, R. B., Kannel, W. B., et al. (2002). Lifetime risk for develo** congestive heart failure: The Framingham heart study. Circulation, 106, 3068–3072.

    Article  PubMed  Google Scholar 

  2. Ho, K. K., Pinsky, J. L., Kannel, W. B., & Levy, D. (1993). The epidemiology of heart failure: The Framingham Study. Journal of the American College of Cardiology, 22, 6–13.

    Article  Google Scholar 

  3. Chae, C. U., Pfeffer, M. A., Glynn, R. J., Mitchell, G. F., Taylor, J. O., & Hennekens, C. H. (1999). Increased pulse pressure and risk of heart failure in the elderly. JAMA, 281, 634–639.

    Article  CAS  PubMed  Google Scholar 

  4. Middlekauff, H. L. (1997). Mechanisms and implications of autonomic nervous system dysfunction in heart failure. Current Opinion in Cardiology, 12, 265–275.

    Article  CAS  PubMed  Google Scholar 

  5. Zucker, I. H., & Wang, W. (1991). Reflex control of renal sympathetic nervous activity in heart failure. Herz, 16, 82–91.

    CAS  PubMed  Google Scholar 

  6. DiBona, G. F., & Sawin, L. L. (1995). Increased renal nerve activity in cardiac failure: Arterial vs. cardiac baroreflex impairment. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 268, 112–116.

    Google Scholar 

  7. Levine, B., Kalman, J., Mayer, L., Fillit, H. M., & Packer, M. (1990). Elevated circulating levels of tumour necrosis factor in severe chronic heart failure. New England Journal of Medicine, 323, 236–241.

    Article  CAS  PubMed  Google Scholar 

  8. Landmesser, U., Spiekermann, S., Dikalov, S., Tatge, H., Wilke, R., Kohler, C., et al. (2002). Vascular oxidative stress and endothelial dysfunction in patients with chronic heart failure: Role of xanthine-oxidase and extracellular superoxide dismutase. Circulation, 106, 3073–3078.

    Article  CAS  PubMed  Google Scholar 

  9. Shah, A. M., & Channon, K. M. (2004). Free radicals and redox signalling in cardiovascular disease. Heart, 90, 486–487.

    Article  CAS  PubMed  Google Scholar 

  10. Giardano, F. J. (2005). Oxygen, oxidative stress, hypoxia, and heart failure. Journal of Clinical Investigation, 115, 500–508.

    Google Scholar 

  11. Bozkurt, B., Kribbs, S. B., Clubb, F. J., Michael, L. H., Didenko, V. V., Hornsby, P. J., et al. (1998). Pathophysiologically relevant concentrations of tumour necrosis factor-α promote progressive left ventricular dysfunction and remodeling in rats. Circulation, 97, 1382–1391.

    CAS  PubMed  Google Scholar 

  12. Cleland, J. G. F., Gemmell, I., Khand, A., & Body, A. (1999). Is the prognosis of heart failure improving? European Journal of Heart Failure, 1, 229–241.

    Article  CAS  PubMed  Google Scholar 

  13. Horwich, T. B., MacLellan, W. R., & Fonarow, G. C. (2004). Statin therapy is associated with improved survival in ischemic and nonischemic heart failure. Journal of the American College of Cardiology, 43, 642–648.

    Article  CAS  PubMed  Google Scholar 

  14. Liao, J. K., & Laufs, U. (2005). Pleiotropic effects of statins. Annual Review of Pharmacology and Toxicology, 45, 89–118.

    Article  CAS  PubMed  Google Scholar 

  15. Grundy, S. M. (2005). The issue of statin safety: Where do we stand? Circulation, 111, 3016–3019.

    Article  PubMed  Google Scholar 

  16. Gotto, A. M. (2006). Statins, cardiovascular disease and drug safety. American Journal of Cardiology, 97, 3C–5C.

    PubMed  Google Scholar 

  17. Vaidya, A. B. (1994). Terminalia arjuna in cardiovascular therapy. The Journal of the Association of Physicians of India, 42, 281–282.

    CAS  PubMed  Google Scholar 

  18. Gupta, R., Singhal, S., Goyle, A., & Sharma, V. N. (2001). Antioxidant and hypocholesterolemic effects of Terminalia arjuna tree-bark powder: A randomized placebo-controlled trial. The Journal of the Association of Physicians of India, 49, 231–235.

    CAS  PubMed  Google Scholar 

  19. Dwivedi, S. (1994). Antianginal and cardioprotective effects of Terminalia arjuna, an indigenous drug, in coronary heart disease. The Journal of the Association of Physicians of India, 42, 287–289.

    CAS  PubMed  Google Scholar 

  20. Teerlink, J. R., Pfeffer, J. M., & Pfeffer, M. A. (1998). Effect of left ventricular sphericity on the evolution of ventricular dysfunction in rats with diffuse isoproterenol-induced myocardial necrosis. Journal of Cardiac Failure, 4, 45–56.

    Article  CAS  PubMed  Google Scholar 

  21. Grimm, D., Elsner, D., Schunkert, H., Pfeffer, M., Griese, D., Bruckschlegel, G., et al. (1998). Development of heart failure following isoproterenol administration in the rat: Role of the renin- angiotensin system. Cardiovascular Research, 37, 91–100.

    Article  CAS  PubMed  Google Scholar 

  22. Hayashidani, S., Tsutsui, H., Shiomi, T., Suematsu, N., Kinugawa, S., Ide, T., et al. (2002). Fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor, attenuates left ventricular remodeling and failure after experimental myocardial infarction. Circulation, 105, 868–873.

    Article  CAS  PubMed  Google Scholar 

  23. Gauthaman, K., Maulik, M., Kumari, R., Manchanda, S. C., Dinda, A. K., & Maulik, S. K. (2001). Effect of chronic treatment with bark of Terminalia Arjuna: A study on the isolated ischemic-reperfused rat heart. Journal of Ethnopharmacology, 75, 197–201.

    Article  CAS  PubMed  Google Scholar 

  24. Bos, R., Mougenot, N., Findji, L., Médiani, O., Vanhoutte, P. M., & Lechat, P. (2005). Inhibition of catecholamine-induced cardiac fibrosis by an aldosterone antagonist. Journal of Cardiovascular Pharmacology, 45, 8–13.

    Article  CAS  PubMed  Google Scholar 

  25. Rona, G. (1985). Catecholamine cardiotoxicity. Journal of Molecular and Cellular Cardiology, 17, 291–306.

    Article  CAS  PubMed  Google Scholar 

  26. Yeager, J. C., & Iams, S. G. (1981). The hemodynamics of isoproterenol-induced cardiac failure in the rat. Circulatory Shock, 8, 151–163.

    CAS  PubMed  Google Scholar 

  27. Dhalla, K. S., Rupp, H., Beamish, R. E., & Dhalla, N. S. (1996). Mechanisms of alterations in cardiac membrane Ca2+ transport due to excess catecholamines. Cardiovascular Drugs and Therapy, 10, 231–238.

    Article  PubMed  Google Scholar 

  28. Singal, P. K., Beamich, R. E., & Dhalla, N. S. (1983). Potential oxidative pathways of catecholamines in the formation of lipid peroxides and genesis of heart disease. Advances in Experimental Medicine and Biology, 161, 391–440.

    CAS  PubMed  Google Scholar 

  29. Grimm, D., Holmer, S. R., Riegger, G. A. J., & Kromer, E. P. (1999). Effects of beta-receptor blockade and angiotensin II type I receptor antagonism in isoproterenol- induced heart failure in the rat. Cardiovascular Pathology, 8, 315–323.

    Article  CAS  PubMed  Google Scholar 

  30. Balakumar, P., & Singh, M. (2006). The possible role of caspase-3 in pathological and physiological cardiac hypertrophy in rats. Basic and Clinical Pharmacology and Toxicology, 99, 418–424.

    Article  CAS  PubMed  Google Scholar 

  31. Zhong, D. Z., Min, C. X., Siyu, S., Dan, D., & Hui, C. (2008). From neuroendocrine activation to intracardiac cyclic nucleotides in chronic heart failure of rats induced by isoproterenol. Journal of Chinese Clinical Medicine, 3, 601–608.

    Google Scholar 

  32. Yeager, J. C., & Whitehurst, M. E. (1982). Verapamil prevents isoproterenol induced cardiac failure in rats. Life Sciences, 30, 299–306.

    Article  CAS  PubMed  Google Scholar 

  33. Teerlink, J. R., Pfeffer, J. M., & Pfeffer, M. A. (1994). Progressive ventricular remodeling in response to diffuse isoproterenol- induced myocardial necrosis in rats. Circulation Research, 75, 105–113.

    CAS  PubMed  Google Scholar 

  34. Nirmala, C., & Puvanakrishnan, R. (1996). Protective role of curcumin against isoproterenol induced myocardial infarction in rats. Molecular and Cellular Biochemistry, 159, 85–93.

    Article  CAS  PubMed  Google Scholar 

  35. Zhou, R., Xu, Q., Zheng, P., Yan, L., Zheng, J., & Dai, G. (2008). Cardioprotective effect of fluvastatin on Isoproterenol-induced myocardial infarction in rat. European Journal of Pharmacology, 586, 244–250.

    Article  CAS  PubMed  Google Scholar 

  36. Kumar, S., Enjamoori, R., Jaiswal, A., Ray, R., Seth, S., & Maulik, S. K. (2009). Catecholamine-induced myocardial fibrosis and oxidative stress is attenuated by Terminalia arjuna (Roxb.). The Journal of Pharmacy and Pharmacology, 61, 1529–1536.

    CAS  PubMed  Google Scholar 

  37. Rajadurai, M., & Prince, P. S. M. (2006). Preventive effect of naringin on lipids, lipoproteins and lipid metabolic enzymes in isoproterenol-induced myocardial infarction in Wistar rats. Journal of Biochemical and Molecular Toxicology, 20, 191–197.

    Article  CAS  PubMed  Google Scholar 

  38. Mann, D. L. (2005). Targeted anticytokine therapy and the failing heart. American Journal of Cardiology, 95, 9–16.

    Article  Google Scholar 

  39. Node, K., Fujita, M., Kitakaze, M., Hori, M., & Liao, J. K. (2003). Short-term statin therapy improves cardiac function and symptoms in patients with idiopathic dilated cardiomyopathy. Circulation, 108, 839–843.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

Authors would like to acknowledge Professor M.S.Y. Khan, Jamia Hamdard (India) for providing T. arjuna bark extract and Central Council for Research in Unani Medicine (CCRUM, Government of India) for providing partial financial assistance for the present work.

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  1. Mohammad Fahim

    Present address: Centre for Physiotherapy and Rehabilitation Sciences, Jamia Millia Islamia, Delhi, 110025, India

Authors and Affiliations

  1. Department of Physiology, Maulana Azad Medical College, University of Delhi, Delhi, 110002, India

    Adila Parveen & Rashmi Babbar

  2. Department of Biochemistry, Maulana Azad Medical College, University of Delhi, Delhi, 110002, India

    Sarita Agarwal

  3. Department of Pharmacology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, 110007, India

    Anita Kotwani

  4. Department of Physiology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, 110007, India

    Mohammad Fahim

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Correspondence to Mohammad Fahim.

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Parveen, A., Babbar, R., Agarwal, S. et al. Mechanistic Clues in the Cardioprotective Effect of Terminalia Arjuna Bark Extract in Isoproterenol-Induced Chronic Heart Failure in Rats. Cardiovasc Toxicol 11, 48–57 (2011). https://doi.org/10.1007/s12012-010-9099-2

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