Advanced SearchSearch Tips
Terminalia arjuna Bark and inotropic therapy for heart failure
facebook(new window)  Pirnt(new window) E-mail(new window) Excel Download
  • Journal title : TANG [HUMANITAS MEDICINE]
  • Volume 2, Issue 3,  2012, pp.21.1-21.8
  • Publisher : Association of Humanitas Medicine
  • DOI : 10.5667/tang.2012.0021
 Title & Authors
Terminalia arjuna Bark and inotropic therapy for heart failure
Liu, Shi Jesse;
  PDF(new window)
Heart disease that ultimately leads to heart failure (HF) has been the number one cause of death in the United States as well as in many other countries for over a century. Inotropic therapy utilizing cardiotonics to increase cardiac contractility remains a significant component of the management of HF. However, adverse effects of currently available cardiotonics have been compromising their therapeutic value and often lead to further myocardial dysfunction. Thus, discovery of safe cardiotonics remains a main challenge to improvement of inotropic therapy for HF. This review briefly summarized cellular mechanisms underlying the inotropic action of currently available cardiotonics, newly-developed carditonics and the bark of Terminalia arjuna (TA), a tropical tree used in ayurvedic medicine. The potential of TA bark as a new cardiotonic in inotropic treatment for HF was also discussed.
inotropic therapy;heart failure;ayurvedic medicine;cardiotonic;naturoceutical;neutralceutical;contractility;
 Cited by
Adamopoulos S, Parissis JT, Iliodromitis EK, Paraskevaidis I, Tsiapras D, Farmakis D, Karatzas D, Gheorghiade M, Filippatos GS, Kremastinos DT. Effects of levosimendan versus dobutamine on inflammatory and apoptotic pathways in acutely decompensated chronic heart failure. Am J Cardiol. 2006;98:102-106. crossref(new window)

Ahern TP, Lash TL, Sorensen HT, Pedersen LA. Digoxin treatment is associated with an increased incidence of breast cancer: a population-based case-control study. Breast Cancer Res. 2008;10:R102.

Ahmed A, Rich MW, Fleg JL, Zile MR, Young JB, Kitzman DW, Love TE, Aronow WS, Adams KF, Gheorghiade M. Effects of digoxin on morbidity and mortality in diastolic heart failure: the ancillary digitalis investigation group trial. Circulation. 2006;114:397-403. crossref(new window)

Akita T, Joyner RW, Lu C, Kumar R, Hartzell HC. Developmental changes in modulation of calcium currents of rabbit ventricular cells by phosphodiesterase inhibitors. Circulation. 1994;90:469-478. crossref(new window)

Ali A, Kaur G, Hayat K, Ali M, Ather M, Ali A, Kaur G, Hayat K, Ali M, Ather M. A novel naphthanol glycoside from Terminalia arjuna with antioxidant and nitric oxide inhibitory activities. Pharmazie. 2003;58:932-934.

Arispe N, Diaz JC, Simakova O, Pollard HB. Heart failure drug digitoxin induces calcium uptake into cells by forming transmembrane calcium channels. PNAS. 2008;105:2610-2615. crossref(new window)

Banfor PN, Preusser LC, Campbell TJ, Marsh KC, Polakowski JS, Reinhart GA, Cox BF, Fryer RM. Comparative effects of levosimendan, OR-1896, OR-1855, dobutamine, and milrinone on vascular resistance, indexes of cardiac function, and O2 consumption in dogs. Am J Physiol. 2008;294:H238-H248.

Bharani A, Ganguli A, Mathur LK, Jamra Y, Raman PG. Efficacy of Terminalia arjuna in chronic stable angina: a double-blind, placebo-controlled, crossover study comparing Terminalia arjuna with isosorbide mononitrate. Indian Heart J. 2002;54:170-175.

Bharani A, Ganguly A, Bhargava KD. Salutary effect of Terminalia Arjuna in patients with severe refractory heart failure. Int J Cardiol. 1995;49:191-199. crossref(new window)

Braunwald E. The Management of heart failure: the past, the present, and the future. Circ Heart Fail. 2008;1:58-62. crossref(new window)

Brixius K, Pietsch M, Hoischen S, Müller-Ehmsen J, Schwinger RHG. Effect of inotropic interventions on contraction and Ca2+ transients in the human heart. J Appl Physiol. 1997;83:652-660. crossref(new window)

Campia U, Nodari S, Gheorghiade M. Acute heart failure with low cardiac output: can we develop a short-term inotropic agent that does not increase adverse events? Current Heart Fail Rep. 2010;7:100-109. crossref(new window)

Chen Q, Camara AKS, Rhodes SS, Riess ML, Novalija E, Stowe DF. Cardiotonic drugs differentially alter cytosolic [Ca2+] to left ventricular relationships before and after ischemia in isolated guinea pig hearts. Cardiovasc Res. 2003;59:912-925. crossref(new window)

Cleland J,GF, Teerlink JR, Senior R, Nifontov EM, Mc Murray J,JV, Lang CC, Tsyrlin VA, Greenberg BH, Mayet J, Francis DP, Shaburishvili T, Monaghan M, Saltzberg M, Neyses L, Wasserman SM, Lee JH, Saikali KG, Clarke CP, Goldman JH, Wolff AA, Malik FI. The effects of the cardiac myosin activator, omecamtiv mecarbil, on cardiac function in systolic heart failure: a double-blind, placebo-controlled, crossover, dose-ranging phase 2 trial. The Lancet. 2011;378:676-683. crossref(new window)

Colucci WS, Sawyer DB, Singh K, Communal C. Adrenergic overload and apoptosis in heart failure: implications for therapy. J Card Fail. 2000;6:1-7. crossref(new window)

Communal C, Singh K, Pimentel DR, Colucci WS. Norepinephrine stimulates apoptosis in adult rat ventricular myocytes by activation of the ${\beta}$-adrenergic pathway. Circulation. 1998;98:1329-1334. crossref(new window)

Curran J, Hinton MJ, Rios E, Bers DM, Shannon TR. ${\beta}$-Adrenergic enhancement of sarcoplasmic reticulum calcium leak in cardiac myocytes is mediated by calcium/calmodulin-dependent protein kinase. Circ Res. 2007;100:391-398. crossref(new window)

Delaney A, Bradford C, McCaffrey J, Bagshaw SM, Lee R. Levosimendan for the treatment of acute severe heart failure: A meta-analysis of randomised controlled trials. Int J Cardiol. 2010;138:281-289. crossref(new window)

Ding B, Abe Ji, Wei H, Huang Q, Walsh RA, Molina CA, Zhao A, Sadoshima J, Blaxall BC, Berk BC, Yan C. Functional role of phosphodiesterase 3 in cardiomyocyte apoptosis: implication in heart failure. Circulation. 2005;111:2469-2476. crossref(new window)

Ding G, Wiegerinck RF, Shen M, Cojoc A, Zeidenweber CM, Wagner MB. Dopamine increases L-type calcium current more in newborn than adult rabbit cardiomyocytes via D1 and ${\beta}2$ receptors. Am J Physiol. 2008;294:H2327-H2335.

Dwivedi S, Aggarwal A, Agarwal MP, Rajpal S. Role of Terminalia arjuna in ischaemic mitral regurgitation. Int J Cardiol. 2005;100:507-508. crossref(new window)

Edes I, Kiss E, Kitada Y, Powers FM, Papp JG, Kranias EG, Solaro RJ. Effects of Levosimendan, a cardiotonic agent targeted to troponin C, on cardiac function and on phosphorylation and Ca2+ sensitivity of cardiac myofibrils and sarcoplasmic reticulum in guinea pig heart. Circ Res. 1995;77:107-113. crossref(new window)

Endoh M. The effects of various drugs on the myocardial inotropic response. Gen Pharmacol. 1995;26:1-31. crossref(new window)

Felker GM, O'Connor CM. Inotropic therapy for heart failure: An evidence-based approach. Am Heart J. 2001;142:393-401. crossref(new window)

Gauthaman K, Maulik M, Kumari R, Manchanda SC, Dinda AK, Maulik SK. Effect of chronic treatment with bark of Terminalia arjuna: a study on the isolated ischemic-reperfused rat heart. J Ethnopharmacol. 2001;75:197-201. crossref(new window)

Gheorghiade M, Teerlink JR, Mebazaa A. Pharmacology of new agents for acute heart failure syndromes. Am J Cardiol. 2005;96:68-73. crossref(new window)

Hasenfuss G, Teerlink JR. Cardiac inotropes: current agents and future directions. Euro Heart J. 2011;32:1838-1845. crossref(new window)

Hatem SN, Coulombe A, Balse E. Specificities of atrial electrophysiology: Clues to a better understanding of cardiac function and the mechanisms of arrhythmias. J Mol Cell Cardiol. 2010;48:90-95. crossref(new window)

Holubarsch C, Hasenfuss G, Just H, Alpert NR. Positive inotropism and myocardial energetics: Influence of ${\beta}$ receptor agonist stimulation, phosphodiesterase inhibition, and ouabain. Cardiovasc Res. 1994;28:994-1002. crossref(new window)

Jain S, Yadav P, Gill V, Vasudeva N, Singla N. Terminalia arjuna a sacred medicinal plant: phytochemical and pharmacological profile. Phytochem Rev. 2009;8:491-502. crossref(new window)

Joseph J, Gilbert EM. The sympathetic nervous system in chronic heart failure. Prog Cardiovasc Dis. 1998;41:9-16. crossref(new window)

Kapur S, Aistrup GL, Sharma R, Kelly JE, Arora R, Zheng J, Veramasuneni M, Kadish AH, Balke CW, Wasserstrom JA. Early development of intracellular calcium cycling defects in intact hearts of spontaneously hypertensive rats. Am J Physiol. 2010;299:H1843-H1853.

Karthikeyan K, Sarala Bai BR, Gauthaman K, Sathish KS, Devaraj SN. Cardioprotective effect of the alcoholic extract of Terminalia arjuna bark in an in vivo model of myocardial ischemic reperfusion injury. Life Sci. 2003;73:2727-2739. crossref(new window)

Katz AM. The "modern" view of heart failure: how did we get here? Circ Heart Fail. 2008;1:63-71. crossref(new window)

Korge P, Langer GA. Mitochondrial Ca2+ uptake, efflux, and sarcolemmal damage in Ca2+-overloaded cultured rat cardiomyocytes. Am J Physiol. 1998;274:H2085-H2093.

Kuo PL, Hsu YL, Lin TC, Lin LT, Chang JK, Lin CC. Casuarinin from the bark of Terminalia arjuna induces apoptosis and cell cycle arrest in human breast adenocarcinoma MCF-7 cells. Planta Med. 2005;71:237-243. crossref(new window)

Layland J, Solaro RJ, Shah AM. Regulation of cardiac contractile function by troponin I phosphorylation. Cardiovasc Res. 2005;66:12-21. crossref(new window)

Le Grand B, Deroubaix E, Coulombe A, Coraboeuf E. Stimulatory effect of ouabain on T- and L-type calcium currents in guinea pig cardiac myocytes. Am J Physiol. 1990;258:H1620-H1623.

Lederer WJ, Tsien RW. Transient inward current underlying arrhythmogenic effects of cardiotonic steroids in Purkinje fibres. J Physiol. 1976;263:73-100. crossref(new window)

Lee CO. 200 years of digitalis: the emerging central role of the sodium ion in the control of cardiac force. Am J Physiol. 1985;249:C367-C378. crossref(new window)

Lehnart S, Maier L, Hasenfuss G. Abnormalities of calcium metabolism and myocardial contractility depression in the failing heart. Heart Fail Rev. 2009;14:213-224. crossref(new window)

Lucke JC, Elbeery JR, Koutlas TC, Gall SA,Jr., D'Amico TA, Maier GW, Rankin JS, Glower DD. Effects of cardiac glycosides on myocardial function and energetics in conscious dogs. Am J Physiol. 1994;267:H2042-H2049.

Maack C, Cortassa S, Aon MA, Ganesan AN, Liu T, O'Rourke B. Elevated cytosolic Na+ decreases mitochondrial Ca2+ uptake during excitation-contraction coupling and impairs energetic adaptation in cardiac myocytes. Circ Res. 2006;99:172-182. crossref(new window)

Malik FI, Hartman JJ, Elias KA, Morgan BP, Rodriguez H, Brejc K, Anderson RL, Sueoka SH, Lee KH, Finer JT, Sakowicz R, Baliga R, Cox DR, Garard M, Godinez G, Kawas R, Kraynack E, Lenzi D, Lu PP, Muci A, Niu C, Qian X, Pierce DW, Pokrovskii M, Suehiro I, Sylvester S, Tochimoto T, Valdez C, Wang W, Katori T, Kass DA, Shen Y, Vatner SF, Morgans DJ. Cardiac myosin activation: a potential therapeutic approach for systolic heart failure. Science. 2011;331:1439-1443. crossref(new window)

Marban E, Robinson SW, Wier WG. Mechanisms of arrhythmogenic delayed and early afterdepolarizations in ferret ventricular muscle. J Clin Invest. 1986;78:1185-1192. crossref(new window)

McGarry SJ, Williams AJ. Digoxin activates sarcoplasmic reticulum Ca2+-release channels: A possible role in cardiac inotropy. Br J Pharmacol. 1993;108:1043-1050. crossref(new window)

Medford RM. Digitalis and the Na+,K(+)-ATPase. Heart Dis Stroke. 1993;2:250-255.

Metra M, Bettari L, Carubelli V, Bugatti S, Dei Cas A, Del Magro F, Lazzarini V, Lombardi C, Dei Cas L. Use of inotropic agents in patients with advanced heart failure: lessons from recent trials and hopes for new agents. Drugs. 2011;71:515-525. crossref(new window)

Micheletti R, Palazzo F, Barassi P, Giacalone G, Ferrandi M, Schiavone A, Moro B, Parodi O, Ferrari P, Bianchi G. Istaroxime, a stimulator of sarcoplasmic reticulum calcium adenosine triphosphatase isoform 2a activity, as a novel therapeutic approach to heart failure. Am J Cardiol. 2007;99:24A-32A. crossref(new window)

Miller AL. Botanical influences on cardiovascular disease. Altern Med Rev. 1998;3:422-431.

Nagpal A, Meena L, Kaur S, Grover I, Wadhwa R, Kaul S. Growth suppression of human transformed cells by treatment with bark extracts from a medicinal plant, Terminalia arjuna. In Vitro Cell & Devel Biol - Animal. 2000;36:544-547. crossref(new window)

Nam GB, Burashnikov A, Antzelevitch C. Cellular mechanisms underlying the development of catecholaminergic ventricular tachycardia. Circulation. 2005;111:2727-2733. crossref(new window)

Nammi S, Gudavalli R, Babu BS, Lodagala DS, Boini KM, Nammi S, Gudavalli R, Babu B,S.Ravindra, Lodagala DS, Boini KM. Possible mechanisms of hypotension produced 70% alcoholic extract of Terminalia arjuna (L.) in anaesthetized Nony P, Boissel JP, Lievre M, Leizorovicz A, Haugh MC, Fareh S, Breyne B. Evaluation of the effect of phosphodiesterase inhibitors on mortality in chronic heart failure patients. Eur J Clin Pharmacol. 1994;46:191-196. crossref(new window)

Oberoi L, Akiyama T, Lee KH, Liu SJ. The aqueous extract, not organic extracts, of Terminalia arjuna bark exerts cardiotonic effect on adult ventricular myocytes. Phytomed. 2011;18:259-265. crossref(new window)

O'Connor CM, Gattis WA, Uretsky BF, Adams Jr KF, McNulty SE, Grossman SH, McKenna WJ, Zannad F, Swedberg K, Gheorghiade M, Califf RM. Continuous intravenous dobutamine is associated with an increased risk of death in patients with advanced heart failure: Insights from the Flolan International Randomized Survival Trial (FIRST). Am Heart J. 1999;138:78-86. crossref(new window)

Osadchii OE, Norton GR, McKechnie R, Deftereos D, Woodiwiss AJ. Cardiac dilatation and pump dysfunction without intrinsic myocardial systolic failure following chronic ${\beta}$-adrenoreceptor activation. Am J Physiol Heart Circ Physiol. 2007;292:H1898-H1905. crossref(new window)

Packer M, Carver JR, Rodeheffer RJ, Ivanhoe RJ, DiBianco R, Zeldis SM, Hendrix GH, Bommer WJ, Elkayam U, Kukin ML. Effect of oral milrinone on mortality in severe chronic heart failure. The PROMISE Study Research Group. N Engl J Med. 1991;325:1468-1475. crossref(new window)

Pawar RS, Bhutani KK. Effect of oleanane triterpenoids from Terminalia arjuna - a cardioprotective drug on the process of respiratory oxyburst. Phytomed. 2005;12:391-393. crossref(new window)

Radhakrishnan R, Wadsworth RM, Gray AI. Terminalia arjuna, an ayurvedic cardiotonic, increases contractile force of rat isolated atria. Phytother Res. 1993;7:266-268. crossref(new window)

Rendig SV, Amsterdam EA. Comparison of positive inotropic effects of milrinone, dobutamine and ouabain. Cardiology. 1994;84:99-105.

Rocchetti M, Alemanni M, Mostacciuolo G, Barassi P, Altomare C, Chisci R, Micheletti R, Ferrari P, Zaza A. Modulation of sarcoplasmic reticulum function by PST2744 [istaroxime; (e,z)-3-((2-aminoethoxy)imino) androstane-6,17- dione hydrochloride)] in a pressure-overload heart failure model. J Pharmacol Exp Ther. 2008;326:957-965. crossref(new window)

Rocchetti M, Besana A, Mostacciuolo G, Micheletti R, Ferrari P, Sarkozi S, Szegedi C, Jona I, Zaza A. Modulation of sarcoplasmic reticulum function by Na+/K+ pump inhibitors with different toxicity: Digoxin and PST2744 [(E,Z)-3-((2-Aminoethoxy)imino)androstane-6,17-dione Hydr- ochloride]. J Pharmacol Exp Ther. 2005;313:207-215.

Rosca MG, Hoppel CL. Mitochondria in heart failure. Cardiovasc Res. 2010;88:40-50. crossref(new window)

Ruch SR, Nishio M, Wasserstrom JA. Effect of cardiac glycosides on action potential characteristics and contractility in cat ventricular myocytes: Role of calcium overload. J Pharmacol Exp Ther. 2003;307:419-428. crossref(new window)

Sagawa T, Sagawa K, Kelly JE, Tsushima RG, Wasserstrom JA. Activation of cardiac ryanodine receptors by cardiac glycosides. Am J Physiol Heart Circ Physiol. 2002;282:H1118-H1126. crossref(new window)

Shen Y, Malik FI, Zhao X, Depre C, Dhar SK, Abarzúa P, Morgans DJ, Vatner SF. Improvement of cardiac function by a cardiac myosin activator in conscious dogs with systolic heart failure / clinical perspective. Circ Heart Fail. 2010;3:522-527. crossref(new window)

Shizukuda Y, Buttrick PM, Geenen DL, Borczuk AC, Kitsis RN, Sonnenblick EH. ${\beta}$-Adrenergic stimulation causes cardiocyte apoptosis: influence of tachycardia and hypertrophy. Am J Physiol. 1998;275:H961-H968.

Singh DV, Gupta MM, Tripathi AK, Prajapati V, Kumar S. Arjunetin from Terminalia arjuna as an insect feeding-deterrent and growth inhibitor. Phytother Res. 2004;18:131-134. crossref(new window)

Singh N, Kapur KK, Singh SP, Shanker K, Sinha JN, Kohli RP. Mechanism of cardiovascular action of Terminalia arjuna. Planta Med. 1982;45:102-104. crossref(new window)

Sivalokanathan S, Vijayababu MR, Balasubramanian MP. Effects of Terminalia arjuna bark extract on apoptosis of human hepatoma cell line HepG2. World J Gastroenterol. 2006;12:1018-1024. crossref(new window)

Sorsa T, Heikkinen S, Abbott MB, Abusamhadneh E, Laakso T, Tilgmann C, Serimaa R, Annila A, Rosevear PR, Drakenberg T, Pollesello P, Kilpelainen I. Binding of Levosimendan, a calcium sensitizer, to cardiac troponin C. J Biol Chem. 2001;276:9337-9343. crossref(new window)

Stevenson LW. Inotropic therapy for heart failure. N Engl J Med. 1998;339:1848-1850. crossref(new window)

Stump GL, Wallace AA, Gilberto DB, Gehret JR, Lynch JJ,Jr. Arrhythmogenic potential of positive inotropic agents. Basic Res Cardiol. 2000;95:186-198. crossref(new window)

Teerlink J. A novel approach to improve cardiac performance: cardiac myosin activators. Heart Fail Rev. 2009;14:289-298. crossref(new window)

Teerlink J, Metra M, Zaca V, Sabbah H, Cotter G, Gheorghiade M, Cas L. Agents with inotropic properties for the management of acute heart failure syndromes. Traditional agents and beyond. Heart Fail Rev. 2009;14:243-253. crossref(new window)

The Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med. 1997;336:525-533. crossref(new window)

Toma M, Starling R. Inotropic therapy for end-stage heart failure patients. Curr Treat Options in Cardiovas Med. 2010;12:409-419. crossref(new window)

Tomita H, Nazmy M, Kajimoto K, Yehia G, Molina CA, Sadoshima J. Inducible cAMP early repressor (icer) is a negative-feedback regulator of cardiac hypertrophy and an important mediator of cardiac myocyte apoptosis in response to ${\beta}$-adrenergic receptor stimulation. Circ Res. 2003;93:12-22. crossref(new window)

Trautwein W, Hescheler J. Regulation of cardiac L-type calcium current by phosphorylation and G proteins. Annu Rev Physiol. 1990;52:257-274. crossref(new window)

Tweedie D, Harding SE, MacLeod KT. Sarcoplasmic reticulum Ca content, sarcolemmal Ca influx and the genesis of arrhythmias in isolated guinea-pig cardiomyocytes. J Mol Cell Cardiol. 2000;32:261-272. crossref(new window)

Verkerk AO, Veldkamp MW, Baartscheer A, Schumacher CA, Klopping C, van Ginneken ACG, Ravesloot JH. Ionic mechanism of delayed afterdepolarizations in ventricular cells isolated from human end-stage failing hearts. Circulation. 2001;104:2728-2733. crossref(new window)

Wakita Y. Inotropic, Chronotropic, and Arrhythmogenic Effects of dopamine on the isolated working heart of rabbit. J Physiol Sci. 2007;57:147-157. crossref(new window)

Wier WG, Hess P. Excitation-contraction coupling in cardiac Purkinje fibers. Effects of cardiotonic steroids on the intracellular [Ca2+] transient, membrane potential, and contraction. J Gen Physiol. 1984;83:395-415. crossref(new window)

Yano M, Kohno M, Ohkusa T, Mochizuki M, Yamada J, Hisaoka T, Ono K, Tanigawa T, Kobayashi S, Matsuzaki M. Effect of milrinone on left ventricular relaxation and Ca2+ uptake function of cardiac sarcoplasmic reticulum. Am J Physiol Heart Circ Physiol. 2000;279:H1898-H1905. crossref(new window)

Yatani A, Brown AM. Rapid ${\beta}$-adrenergic modulation of cardiac calcium channel currents by a fast G protein pathway. Science. 1989;245:71-74. crossref(new window)

Zhao H, Matsuoka s, Fujioka Y, Noma A. Effects of dopamine on L-type Ca2+ current in single atrial and ventricular myocytes of the rat. Br J Pharmacol. 1997;121:1247-1254. crossref(new window)