The Effect of 17-methoxyl-7-hydroxy-benzene-furanchalcone Isolated from Millettia pulchra on Myocardial Ischemia In Vitro and In Vivo

Abstract

The effect of 17-methoxyl-7-hydroxy-benzene-furanchalcone isolated from the roots of Millettia pulchra (Benth.) Kurz var. Laxior (Dunn) Z. Wei on rat myocardial ischemia has been investigated. An in vitro cardiocyte apoptosis model and an in vivo myocardial ischemia model were used to elucidate the mechanism of 17-methoxyl-7-hydroxy-benzene-furanchalcone. In contrast to hydrogen peroxide (H₂O₂, 100 µmol/L), 17-methoxyl-7-hydroxy-benzene-furanchalcone in vitro (255 and 510 µmol/L) increased the quantity of total superoxide dismutase and the protein expression of B cell lymphoma/leukemia-2, while it inhibited cardiocyte apoptosis, the release of malondialdehyde and tumor necrosis factor α, and protein expression of nuclear factor κ Bp65 and Bcl-2-associated X protein. Furthermore, pretreatment with MHBFC in vivo (10 and 20 mg/kg) decreased heart rate, systolic pressure, diastolic pressure, average pressure, left ventricular systolic pressure, the largest upstroke velocity of the left ventricular pressure (+ dp/dt_max), total antioxidative capability, myoglobin isoenzyme of creatine kinase, and inducible nitric oxide synthase, while it increased endothelial nitric oxide synthase, ATPases, left ventricular diastolic pressure, left ventricular end-diastolic pressure, the largest descendent velocity of the left ventricular pressure (−dp/dt_max) and the interval from the beginning of left ventricular contraction to +dp/dt_max (t − dp/dt_max), all in a dose-dependent manner. Our present results suggest that 17-methoxyl-7-hydroxy-benzene-furanchalcone is an attractive antimyocardial ischemia agent mostly because of its negative heart rate and negative inotropic effects, the reduction in myocardial oxidative damage, and the modulating expression of genes associated with apoptosis, which improves diastolic function.

Key words

17-methoxyl-7-hydroxy-benzene-furanchalcone - Millettia pulchra Papilionaceae - myocardial ischemia - apoptosis - peroxidation - cardiac hemodynamics

^* These authors contributed equally to this work.

• References

• 1 Lee YM, Cheng PY, Chen SY, Chung MT, Sheu JR. Wogonin suppresses arrhythmias, inflammatory responses, and apoptosis induced by myocardial ischemia/reperfusion in rats. J Cardiovasc Pharm 2011; 58: 133-142
• 2 Sanada S, Komuro I, Kitakaze M. Pathophysiology of myocardial reperfusion injury: preconditioning, postconditioning, and translational aspects of protective measures. Am J Physiol Heart Circ Physiol 2011; 301: 1723-1741
• 3 Bigalke B, Stellos K, Geisler T, Kremmer E, Seizer P. Expression of platelet glycoprotein VI is associated with transient ischemic attack and stroke. Eur J Neurol 2010; 17: 111-117
• 4 Matejikova J, Kucharska J, Pinterova M, Pancza D, Ravingerova T. Protection against ischemia-induced ventricular arrhythmias and myocardial dysfunction conferred by preconditioning in the rat heart: involvement of mitochondrial K⁺-ATP channels and reactive oxygen species. Physiol Res 2009; 58: 9-19
• 5 Bagatini MD, Martins CC, Battisti V, Gasparetto D, Darosa CS. Oxidative stress versus antioxidant defenses in patients with acute myocardial infarction. Heart Vessels 2011; 26: 55-63
• 6 Gottlieb RA. Cell death pathways in acute ischemia/reperfusion injury. J Cardiovasc Pharmacol Ther 2011; 16: 233-238
• 7 Hori M, Nishida K. Oxidative stress and left ventricular remodelling after myocardial infarction. Cardiovasc Res 2009; 81: 457-464
• 8 Deeks ED, Keating GM, Keam SJ. Clevidipine: a review of its use in the management of acute hypertension. Am J Cardiovasc Drugs 2009; 9: 117-134
• 9 Zellweger MJ, Pfisterer ME. Therapeutic strategies in patients with chronic stable coronary artery disease. Cardiovasc Ther 2011; 29: e23-e30
• 10 Chen J, Chen X, Qin J. Effects of polysaccharides of the Euphoria longan (Lour.) Steud on focal cerebral ischemia/reperfusion injury and its underlying mechanism. Brain Inj 2011; 25: 292-299
• 11 Zhang JH, Chen ZW, Wu Z. Late protective effect of pharmacological preconditioning with total flavones of rhododendra against myocardial ischemia-reperfusion injury. Can J Physiol Pharm 2008; 86: 131-138
• 12 Jian J, Huang JC, Jiao Y, Tan HD, Huang RB. Isolation and preparation of chalcone compounds from tuber of Millettia pulchra var. laxior by pre-HPLC. Chin Tradit Herb Drugs 2011; 42: 1313-1316
• 13 Jian J, Li YW, Jiang WZ, Huang RB. The effects of two chalcone monomers from Yulangsan on scavenging free radicals. Chin J Gerontol 2009; 29: 2353-2354
• 14 Jian J, Liu X, Huang RB. Protection and its mechanism of two flavone morphons from Yulangsan on hypoxia-reoxygenation induced injury in myocardial cells. Chin Pharm Bull 2009; 7: 942-945
• 15 Cai XY, Lu L, Wang YN, Jin C, Zhang RY, Zhang Q, Chen QJ, Shen WF. Association of increased S100B, S100A6 and S100P in serum levels with acute coronary syndrome and also with the severity of myocardial infarction in cardiac tissue of rat models with ischemia-reperfusion injury. Atherosclerosis 2011; 217: 536-542
• 16 Lorgis L, Zeller M, Dentan G, Sicard P, Richard C, Buffet P, Huillier I, Beer JC, Cottin Y, Rochette L, Vergely C. The free oxygen radicals test (FORT) to assess circulating oxidative stress in patients with acute myocardial infarction. Atherosclerosis 2010; 213: 616-621
• 17 Turer AT, Hill JA. Pathogenesis of myocardial ischemia-reperfusion injury and rationale for therapy. Am J Cardiol 2010; 106: 360-368
• 18 Wang J, Zhang QB, Jin WH, Niu XZ, Zhang H. Effects and mechanism of low molecular weight fucoidan in mitigating the peroxidative and renal damage induced by adenine. Carbohydr Polym 2011; 84: 417-423
• 19 Tian XP, Yin YY, Li X. Effects and mechanisms of Acremoniumterricola milleretal mycelium on liver fibrosis induced by carbon tetrachloride in rats. Am J Chin Med 2011; 39: 537-550
• 20 Liu W, Wu SY. Differential roles of nitric oxide synthases in regulation of ultraviolet B light-induced apoptosis. Nitric Oxide 2010; 23: 199-205
• 21 Balaraman G, Sivaprakasam B, Rangasamy J, Rangasamy A. Protective effect of betaine on changes in the levels of membrane-bound ATPase activity and mineral status in experimentally induced myocardial infarction in Wistar rats. Biol Trace Elem Res 2009; 131: 278-290
• 22 Pogorelov AG, Pogorelova VN, Dubrovkin MI. Analysis of elemental composition (Na/K/Ca) of muscle cells in ischemia in a model of the perfused heart. Tsitologiia 2000; 42: 62-65
• 23 Matsumoto T, Hisamatsu Y, Ohkusa T, Inoue N, Sato T, Suzuki S. Sorcin interacts with sarcoplasmic reticulum Ca²⁺-ATPase and modulates excitation-contraction coupling in the heart. Basic Res Cardiol 2005; 100: 250-262
• 24 Asai D, Tsuchiya A, Kang JH, Kawamura K, Oishi J, Mori T, Niidome T, Shoji Y, Nakashima H, Katayama Y. Inflammatory cell-specific transgene expression system responding to I kappa-B kinase beta activation. J Gen Med 2009; 11: 624-632
• 25 Li CM, Gao YL, Xing YL, Zhu HB, Shen JY, Tian JW. Fucoidan, a sulfated polysaccharide from brown algae, against myocardial ischemia-reperfusion injury in rats via regulating the inflammation response. Food Chem Toxicol 2011; 49: 2090-2095
• 26 Bertazza L, Mocellin S. The dual role of tumor necrosis factor (TNF) in cancer biology. Curr Med Chem 2010; 17: 3337-3352
• 27 Bertazza L, Mocellin S. Tumor necrosis factor (TNF) biology and cell death. Front Biosci 2008; 13: 2736-2743
• 28 Portt L, Norman G, Clapp C, Greenwood M, Greenwood MT. Anti-apoptosis and cell survival: a review. Biochim Biophys Acta 2011; 1813: 238-259
• 29 Wyllie AH. “Where, o death, is thy sting?” A brief review of apoptosis biology. Mol Neurobiol 2010; 42: 4-9
• 30 Foadoddini M, Esmailidehaj M, Mehrani H, Sadraei SH, Golmanesh L, Wahhabaghai H, Valen G, Khoshbaten A. Pretreatment with hyperoxia reduces in vivo infarct size and cell death by apoptosis with an early and delayed phase of protection. Eur J Cardiothorac Surg 2011; 39: 233-240