Total flavonoid extract from Coreopsis tinctoria Nutt. protects rats against myocardial ischemia/reperfusion injury

Document Type: Original Article

Authors

1 Ministry of Education, Pharmacy Shihezi University Xinjiang China

2 Pharmacy Shihezi University Xinjiang China

Abstract

Objective(s): This study aimed to evaluate the protective effects of total flavonoid extract from Coreopsis tinctoria Nutt.(CTF)against myocardial ischemia/reperfusion injury (MIRI) using an isolated Langendorff rat heart model.
Materials and Methods: Left ventricular developed pressure (LVDP) and the maximum rate of rise and fall of LV pressure (±dp/dtmax) were recorded. Cardiac injury was assessed by analyzing lactate dehydrogenase (LDH) and creatine kinase (CK) released in the coronary effluent. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) levels were determined. Myocardial inflammation was assessed by monitoring tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), interleukin-8 (IL-8), and interleukin-6 (IL-6) levels. Myocardial infarct size was estimated. Cell morphology was assessed by 2,3,5-triphenyltetrazolium chloride and hematoxylin and eosin (HE) staining. Cardiomyocyte apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining.
Results: Pretreatment with CTF significantly increased the heart rate and increased LVDP, as well as SOD and GSH-Px levels. In addition, CTF pretreatment decreased the TUNEL-positive cell ratio, infarct size, and levels of CK, LDH, MDA, TNF-α, CRP, IL-6, and IL-8.
Conclusion: These results suggest that CTF exerts cardio-protective effects against MIRI via anti-oxidant, anti-inflammatory, and anti-apoptotic activities.

Keywords


1. Zweier JL, Talukder MA. The role of oxidants and free radicals in reperfusion injury. Cardiovasc Res 2006; 70:181-190.

2. Pantos C, Bescond-Jacquet A, Tzeis S, Paizis I, Mourouzis I, Moraitis P, et al. Trimetazidine protects isolated rat hearts against ischemia-reperfusion injury in an experimental timing-dependent manner. Basic Res Cardiol2005; 100:154-160.

3. Najafi M. Effects of postconditioning, preconditioning and perfusion of L-carnitine during  whole period of ischemia/ reperfusion on cardiac hemodynamic functions and myocardial infarction size in isolated rat heart. Iran J Basic Med Sci 2013; 16:648-655.

4. Hoffman JW Jr, Gilbert TB, Poston RS, Silldorff EP. Myocardial reperfusion injury: etiology, mechanisms, and therapies. J Extra Corpor Technol 2004; 36:391-411.

5. Akhlaghi M, Bandy B. Mechanisms of flavonoid protection against myocardial ischemia-reperfusion injury. J Mol Cell Cardiol 2009; 46:309-317.

6. Hodek P, Trefil P, Stiborova M. Flavonoids-potent and versatile biologically active compounds interacting with cytochromes P450. Chem Biol Interact 2002; 139:1-21.

7. Hertog MG, Feskens EJ, Hollman PC, Katan MB, Kromhout D. Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study. Lancet 1993; 342:1007-1011.

8. Mladenka P, Zatloukalova L, Filipsky T, Hrdina R. Cardiovascular effects of flavonoids are not caused only by direct antioxidant activity. Free Radic Biol Med 2010; 49:963-975.

9. Babu PV, Liu D. Green tea catechins and cardiovascular health: an update. Curr Med Chem 2008; 15:1840-1850.

10. Yu D, Li M, Tian Y, Liu J, Shang J. Luteolin inhibits ROS-activated MAPK pathway in myocardial ischemia/reperfusion injury. Life Sci2015; 122:15-25.

11. Hirai M, Hotta Y, Ishikawa N, Wakida Y, Fukuzawa Y, Isobe F, et al.. Protective effects of EGCg or GCg, a green tea catechin epimer, against postischemic myocardial dysfunction in guinea-pig hearts. Life Sci2007; 80:1020-1032.

12. Dias T, Bronze MR, Houghton PJ, Mota-Filipe H, Paulo A. The flavonoid-rich fraction of Coreopsis tinctoria promotes glucose tolerance regain through pancreatic function recovery in streptozotocin-induced glucose-intolerant rats. J Ethnopharmacol 2010; 132:483-490.

13. Sun YH, Zhao J, Jin HT, Cao Y, Ming T, Zhang LL, et al. Vasorelaxant effects of the extracts and some flavonoids from the buds of Coreopsis tinctoria. Pharm Biol 2013; 51:1158-1164.

14. Yao L, Li L, Li X, Li H, Zhang Y, Zhang R, et al. The anti-inflammatory and antifibrotic effects of Coreopsis tinctoria Nutt on high-glucose-fat diet and streptozotocin-induced diabetic renal damage in rats. BMC Complement Alternat Med 2015; 15:314.

15. Lan S, Lin J, Zheng N. Evaluation of the antioxidant activity of Coreopsis tinctoria Nuff. and optimisation of isolation by response surface methodology. Acta Pharm 2014; 64:369-378.

16. Guo LM, Zhang WS, Li SM, Ho CT. Chemical and nutraceutical properties of Coreopsis tinctoria. J Funct Foods 2015; 13:11-20.

17. Li YL, Chen XM, Xue J, Liu JY, Chen XH, Wulasihan M. Flavonoids from Coreopsis tinctoria adjust lipid metabolism in hyperlipidemia animals by down-regulating adipose differentiation-related protein. Lipids Health Dis 2014; 13:193.

18. Zhao P, Qi C, Wang G, Dai XP, Hou XH. Enrichment and purification of total flavonoids from Cortex Juglandis Mandshuricae extracts and their suppressive effect on carbon tetrachloride-induced hepatic injury in Mice. J Chromatogr B 2015; 1007:8-17.

19. Khandoudi N, Laville MP, Bril A. Protective effect of the sodium/hydrogen exchange inhibitors during global low-flow ischemia. J Cardiovasc Pharmacol 1996; 28:540-546.

20. Badavi M, Sadeghi N, Dianat M, Samarbafzadeh A. Effects of gallic Acid and cyclosporine a on antioxidant capacity and cardiac markers of rat isolated heart after ischemia/reperfusion. Iran Red Crescent Med J 2014; 16:e16424.

21. Gottlieb RA, Engler RL. Apoptosis in myocardial ischemia-reperfusion. Ann N Y Acad Sci 1999; 874:412-426.

22. Haunstetter A, Izumo S. Apoptosis: basic mechanisms and implications for  cardiovascular disease. Circ Res 1998; 82:1111-1129.

23. Wang YL, Wang CY, Zhang BJ, Zhang ZZ. Shenfu injection suppresses apoptosis by regulation of Bcl-2 and caspase-3 during hypoxia/reoxygenation in neonatal rat cardiomyocytes in vitro. Mol Biol Rep 2009; 36:365-370.

24. Zhao ZQ, Corvera JS, Halkos ME, Kerendi F, Wang NP, Guyton RA, et al.  Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning. Am J Physiol Heart Circ Physiol 2003; 285:H579-588.

25. Noorbakhsh MF, Arab HA, Kazerani HR. Liver ischemia preconditions the heart against ischemia-reperfusion arrhythmias. Iran J Basic Med Sci 2015; 18:80-88.

26. Yu P, Zhang J, Yu S, Luo Z, Hua F, Yuan L, et al. Protective effect of sevoflurane postconditioning against cardiac ischemia/reperfusion injury via ameliorating mitochondrial impairment, oxidative stress and rescuing autophagic clearance. PloS One 2015; 10:e0134666.

27. Jaeschke H, Woolbright BL. Current strategies to
minimize hepatic ischemia-reperfusion injury by targeting reactive oxygen species. Transplant Rev 2012; 26:103-114.

28. Garciarena CD, Fantinelli JC, Caldiz CI, Chiappe de Cingolani G, Ennis IL, et al.  Myocardial reperfusion injury: reactive oxygen species vs. NHE-1 reactivation. Cell Physiol Biochem 2011; 27:13-22.

29. Lopera YE, Fantinelli J, Gonzalez Arbelaez LF, Rojano B, Rios JL, Schinella G, Mosca S. Antioxidant activity and cardioprotective effect of a nonalcoholic extract of vaccinium meridionale Swartz during ischemia-reperfusion in rats. Evid Based Complement Alternat Med 2013; 2013:516727.

30. Friedrich MG, Abdel-Aty H, Taylor A, Schulz-Menger J, Messroghli D, Dietz R. The salvaged area at risk in reperfused acute myocardial infarction as visualized by cardiovascular magnetic resonance. J Am Coll Cardiol 2008; 51:1581-1587.

31. Mehdizadeh R, Parizadeh MR, Khooei AR, Mehri S, Hosseinzadeh H. Cardioprotective effect of saffron extract and safranal in isoproterenol-induced  myocardial infarction in wistar rats. Iran J Basic Med Sci 2013; 16:56-63.

32. Kupatt C, Habazettl H, Becker BF, Boekstegers P. Endothelial activation- a strategic event during postischemic myocardial inflammation. Z Kardiol 2000; 89:96-100.

33. Liu H, Guo X, Chu Y, Lu S. Heart protective effects and mechanism of quercetin preconditioning on anti-myocardial ischemia reperfusion (IR) injuries in rats. Gene 2014; 545:149-155.

34. Boyle EM, Kovacich JC, Hebert CA, Canty TG, Chi E, Morgan EN, et al.  Inhibition of interleukin-8 blocks myocardial ischemia-reperfusion injury. J Thorac Cardiovasc Surg 1998; 116:114-120.

35. Groot HE, Hartman MH, Gu YL, de Smet BJ, van den Heuvel AF, Lipsic E, et al. Soluble interleukin 6 receptor levels are associated with reduced myocardial reperfusion after percutaneous coronary intervention for acute myocardial infarction. Cytokine 2015; 73:207-212.

36. Kremneva LV, Semukhin MV, Kuznetsov VA. Inflammation as a risk factor for restenosis and cardiovascular complications after transcutaneous intracoronary interventions. Ter Arkh 2006; 78:89-95.

37. Vinten-Johansen J, Jiang R, Reeves JG, Mykytenko J, Deneve J, Jobe LJ. Inflammation, proinflammatory mediators and myocardial ischemia-reperfusion injury.  Hematol Oncol Clin North Am 2007; 21:123.