Protective effect of scutellarin on myocardial infarction induced by isoprenaline in rats

Document Type: Original Article

Authors

1 Apitherapy Institute, College of Bee Science, Fujian Agriculture and Forestry University, Fuzhou, China

2 College of Food Science, Fujian Agriculture and Forestry University, Fuzhou, China

3 State and Local Joint Engineering Laboratory of Natural Biotoxins, Fujian Agriculture and Forestry University, Fuzhou, China

4 Department of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, China

Abstract

Objective(s): Scutellarin (Scu) is the main effective constituent of Erigeron breviscapuswhich hasanti-oxidant, anti-apoptotic, anti-inflammatory and other therapeutic properties. The purpose of this study was to investigate the protective effect of Scu on myocardial infarction (MI) induced by isoprenaline (ISO).
Materials and Methods: The rats were subcutaneously injected with ISO (45 mg/kg) on the first day, then single tail-intravenously injected with different doses of Scu (10 mg/kg, 20 mg/kg, 40 mg/kg) for 7 consecutive days. The protective effect of Scu on ISO-induced MI was evaluated by measuring markers of heart injury in serum, levels of lipid peroxidation, and antioxidants in heart tissue, observing pathological changes of tissue, and detecting quantified expression of apoptotic-related family members and inflammation.
Results: Compared with the model group, the concentration of troponin T (CTn-T) and troponin I (CTn-I), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) in the serum all decreased in the Scu high dose group. The activities of superoxide dismutase (SOD), catalase (CAT), and the content of reduced glutathione (GSH) in heart increased, and the content of malondialdehyde (MDA) and inducible nitric oxide synthase (iNOS) decreased. In addition, the histopathologic aspects showed that pathological heart change was found in the model group, and was reduced to varying degrees in the Scu group. Moreover, the expression of Bax, P53, Caspase3, Caspase9, cytochrome C, NGAL, NFκB, IL-1β and IL-6 in the heart decreased, while the expression of Bcl2 increased.
Conclusion: Scu could reduce the degree of MI induced by ISO by improving the antioxidant, anti-apoptotic, and anti-inflammatory capacities of the body.

Keywords

Main Subjects


1. Awada HK, Johnson NR, Wang Y. Sequential delivery of angiogenic growth factors improves revascularization and heart function after myocardial infarction. J Control Release 2015; 207:7-17.

2. Meena B, Anbu Rajan L, Anandan R. Protective effect of betaine on protein, glycoproteins and amino acids in isoprenaline-induced myocardial infarction in albino rats. Biomed Prev Nutr 2014; 4:403-409.

3. Chen SW, Tung YC, Jung SM, Chu Y, Lin PJ, Kao WW, et al. Lumican-null mice are susceptible to aging and isoproterenol-induced myocardial fibrosis. Biochem Biophys Res Commun 2017; 482:1304-1311.

4. Nagoor Meeran MF, Jagadeesh GS, Selvaraj P. Thymol attenuates altered lipid metabolism in β-adrenergic agonist induced myocardial infarcted rats by inhibiting tachycardia, altered electrocardiogram, apoptosis and cardiac hypertrophy. J Funct Foods 2015; 14:51-62.

5. Tang YN, He XC, Ye M, Huang H, Chen HL, Peng WL, et al. Cardioprotective effect of total saponins from three medicinal species of Dioscorea against isoprenaline-induced myocardial ischemia. J Ethnopharmacol 2015; 175:451-455.

6. Suchal K, Malik S, Gamad N, Malhotra RK, Goyal SN, Bhatia J, et al. Kampeferol protects against oxidative stress and apoptotic damage in experimental model of isoproterenol-induced cardiac toxicity in rats. Phytomedicine 2016; 23:1401-1408.

7. Allijn IE, Czarny BM, Wang X, Chong SY, Weiler M, da Silva AE, et al. Liposome encapsulated berberine treatment attenuates cardiac dysfunction after myocardial infarction. J Control Release 2017; 247:127-133.

8. Haskova P, Jansova H, Bures J, Machacek M, Jirkovska A, Franz KJ, et al. Cardioprotective effects of iron chelator HAPI and ROS-activated boronate prochelator BHAPI against catecholamine-induced oxidative cellular injury. Toxicology 2016; 371:17-28.

9. Raish M. Momordica charantia polysaccharides ameliorate oxidative stress, hyperlipidemia, inflammation, and apoptosis during myocardial infarction by inhibiting the NF-κB signaling pathway. Int J Biol Macromol 2017; 97:544-551.

10. Geng ZH, Huang L, Song MB, Song YM. Protective effect of a polysaccharide from Salvia miltiorrhiza on isoproterenol (ISO)-induced myocardial injury in rats. Carbohydr Polym 2015; 132:638-642.

11. Yasuda J, Okada M, Yamawaki H. T3 peptide, an active fragment of tumstatin, inhibits H2O2-induced apoptosis in H9c2 cardiomyoblasts. Eur J Pharmacol 2017; 807:64-70.

12. Woudstra L, Biesbroek PS, Emmens RW, Heymans S, Juffermans LJ, van Rossum AC, et al. Lymphocytic myocarditis occurs with myocardial infarction and coincides with increased inflammation, hemorrhage and instability in coronary artery atherosclerotic plaques. Int J Cardiol 2017; 232:53-62.

13. De Filippo K, Dudeck A, Hasenberg M, Nye E, van Rooijen N, Hartmann K, et al. Mast cell and macrophage chemokines CXCL1/CXCL2 control the early stage of neutrophil recruitment during tissue inflammation. Blood 2013; 121:4930-4937.

14. Long J, Gao M, Kong Y, Shen X, Du X, Son YO, et al. Cardioprotective effect of total paeony glycosides against isoprenaline-induced myocardial ischemia in rats. Phytomedicine 2012; 19:672-676.

15. E MP, Mopuri R, Pulaganti M, Kareem MA, Islam MS, K RD, et al. Molecular assessment of protective effect of Vitex negundo in ISO induced myocardial infarction in rats. Biomed Pharmacother 2017; 92:249-253.

16. Krushna GS, Shivaranjani VL, Umamaheswari J, Srinivasulu C, Hussain SA, Kareem MA, et al. In vivo and molecular docking studies using whole extract and phytocompounds of Aegle marmelos fruit protective effects against Isoproterenol-induced myocardial infarction in rats. Biomed Pharmacother 2017; 91:880-889.

17. Deng XY, Chen JJ, Li HY, Ma ZQ, Ma SP, Fu Q. Cardioprotective effects of timosaponin B II from Anemarrhenae asphodeloides Bge on isoproterenol-induced myocardial infarction in rats. Chem Biol Interact 2015; 240:22-28.

18. Gao M, Huang W, Liu CZ. Separation of scutellarin from crude extracts of Erigeron breviscapus (vant.) Hand. Mazz. by macroporous resins. J Chromatogr B Analyt Technol Biomed Life Sci 2007; 858:22-26.

19. Chai L, Guo H, Li H, Wang S, Wang YL, Shi F, et al. Scutellarin and caffeic acid ester fraction, active components of Dengzhanxixin injection, upregulate neurotrophins synthesis and release in hypoxia/reoxygenation rat astrocytes. J Ethnopharmacol 2013; 150:100-107.

20. Yao H, Huang X, Shi P, Lin Z, Zhu M, Liu A, et al. DPPH·luminol chemiluminescence system and its application in the determination of scutellarin in pharmaceutical injections and rat plasma with flow injection analysis. Luminescence 2017; 32:588-595.

21. Chu J, Zou C, Li C, Zhang J, Zhao Y, Xu M, et al. Determination of scutellarein in human plasma by enzymatic hydrolysis and liquid chromatograph-triple quadrupole tandem mass spectrometer analysis: Its use in determining the bioequivalence of scutellarin in Chinese volunteers. Eur J Integr Med 2016; 8:519-525.

22. Zhao S, Sun Y, Li X, Wang J, Yan L, Zhang Z, et al. Scutellarin inhibits RANKL-mediated osteoclastogenesis and titanium particle-induced osteolysis via suppression of NF-κB and MAPK signaling pathway. Int Immunopharmacol 2016; 40:458-465.

23. Jiao ZY. Experimental research of the effect and mechanism of Dengzhanhua against myocardial ischemia of canines. Jilin University, Changchun; 2006

24. Zhao GA, Tang RJ, Qi SL. Protective of effect breviscapine combined with ischemic preconditioning on myocardial cell apoptosis induced by myocardial ischemia reperfusion in rabbits. Chin Hosp Pharm J 2010; 30:1806-1808.

25. Wang YX, Yang J, Wang HB, Song HH. Effect of Erigeron breviscapus injection on myocardial ischemia reperfusion injury. J Hainan Med Univ 2015; 21:1188-1190.

26. Gong MY, Du C, Yuan BY. Effects of breviscapine on serum TNF-α and IL-6 in rats with myocardial ischemia reperfusion. Lishizhen Med Mater Med Res 2013; 24:1615-1616.

27. Lin L, Zou H, Chang J. Protective Effects of scutellarin and breviscapine on acute myocardial infarction. China Pharm 2010; 19:12-13.

28. Guo LL, Guan ZZ, Huang Y, Wang YL, Shi JS. The neurotoxicity of β-amyloid peptide toward rat brain is associated with enhanced oxidative stress, inflammation and apoptosis, all of which can be attenuated by scutellarin. Exp Toxicol Pathol 2013; 65:579-584.

29. Wang Z, Yu J, Wu J, Qi F, Wang H, Wang Z, et al. Scutellarin protects cardiomyocyte ischemia-reperfusion injury by reducing apoptosis and oxidative stress. Life Sci 2016; 157:200-207.

30. Wang S, Wang H, Guo H, Kang L, Gao X, Hu L. Neuroprotection of Scutellarin is mediated by inhibition of microglial inflammatory activation. Neuroscience 2011; 185:150-160.

31. Amano S, Arai M, Goto S, Togari A. Inhibitory effect of NPY on isoprenaline-induced osteoclastogenesis in mouse bone marrow cells. Biochim Biophys Acta 2007; 1770:966-973.

32. Anandan R, Ganesan B, Obulesu T, Mathew S, Kumar RS, Lakshmanan PT, et al. Dietary chitosan supplementation attenuates isoprenaline-induced oxidative stress in rat myocardium. Int J Biol Macromol 2012; 51:783-787.

33. Zaafan MA, Zaki HF, El-Brairy AI, Kenawy SA. Protective effects of atorvastatin and quercetin on isoprenaline-induced myocardial infarction in rats. Bull Fac Pharm Cairo Univ 2013; 51:35-41.

34. Radhiga T, Rajamanickam C, Sundaresan A, Ezhumalai M, Pugalendi KV. Effect of ursolic acid treatment on apoptosis and DNA damage in isoproterenol-induced myocardial infarction. Biochimie 2012; 94:1135-1142.

35. Zhang W, Li Y, Ge Z. Cardiaprotective effect of crocetin by attenuating apoptosis in isoproterenol induced myocardial infarction rat model. Biomed Pharmacother 2017; 93:376-382.

36. Niu C, Sheng Y, Yang R, Lu B, Bai Q, Ji L, et al. Scutellarin protects against the liver injury induced by diosbulbin B in mice and its mechanism. J Ethnopharmacol 2015; 164:301-308.

37. Li X, Wang L, Li Y, Bai L, Xue M. Acute and subacute toxicological evaluation of scutellarin in rodents. Regul Toxicol Pharmacol 2011; 60:106-111.

38. Liu Q, Shi Y, Wang Y, Lu J, Cong W, Luo G, et al. Metabolism profile of scutellarin in urine following oral administration to rats by ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry. Talanta 2009; 80:84-91.

39. Tilyek A, Chai C, Hou X, Zhou B, Zhang C, Cao Z, et al. The protective effects of Ribes diacanthum Pall on cisplatin-induced nephrotoxicity in mice. J Ethnopharmacol 2016; 178:297-306.

40. Sun Y, Yang J, Wang LZ, Sun LR, Dong Q. Crocin attenuates cisplatin-induced liver injury in the mice. Hum Exp Toxicol 2014; 33:855-862.

41. Body R, McDowell G, Carley S, Wibberley C, Ferguson J, Mackway-Jones K. A FABP-ulous 'rule out' strategy? Heart fatty acid binding protein and troponin for rapid exclusion of acute myocardial infarction. Resuscitation 2011; 82:1041-1046.

42. Roos A, Hellgren A, Rafatnia F, Hammarsten O, Ljung R, Carlsson AC, et al. Investigations, findings, and follow-up in patients with chest pain and elevated high-sensitivity cardiac troponin T levels but no myocardial infarction. Int J Cardiol 2017; 232:111-116.

43. Akila P, Asaikumar L, Vennila L. Chlorogenic acid ameliorates isoproterenol-induced myocardial injury in rats by stabilizing mitochondrial and lysosomal enzymes. Biomed Pharmacother 2017; 85:582-591.

44. Peer PA, Trivedi PC, Nigade PB, Ghaisas MM, Deshpande AD. Cardioprotective effect of Azadirachta indica A. Juss. on isoprenaline induced myocardial infarction in rats. Int J Cardiol 2008; 126:123-126.

45. Bazmandegan G, Boroushaki MT, Shamsizadeh A, Ayoobi F, Hakimizadeh E, Allahtavakoli M. Brown propolis attenuates cerebral ischemia-induced oxidative damage via affecting antioxidant enzyme system in mice. Biomed Pharmacother 2017; 85:503-510.

46. Wojtunik-Kulesza KA, Oniszczuk A, Oniszczuk T, Waksmundzka-Hajnos M. The influence of common free radicals and antioxidants on development of Alzheimer’s Disease. Biomed Pharmacother 2016; 78:39-49.

47. Kang L, Zhao H, Chen C, Zhang X, Xu M, Duan H. Sappanone A protects mice against cisplatin-induced kidney injury. Int Immunopharmacol 2016; 38:246-251.

48. da Costa MF, Liborio AB, Teles F, Martins Cda S, Soares PM, Meneses GC, et al. Red propolis ameliorates ischemic-reperfusion acute kidney injury. Phytomedicine 2015; 22:787-795.

49. Cagin YF, Erdogan MA, Sahin N, Parlakpinar H, Atayan Y, Polat A, et al. Protective effects of apocynin on cisplatin-induced hepatotoxicity in rats. Arch Med Res 2015; 46:517-526.

50. Othman AI, Elkomy MM, El-Missiry MA, Dardor M. Epigallocatechin-3-gallate prevents cardiac apoptosis by modulating the intrinsic apoptotic pathway in isoproterenol-induced myocardial infarction. Eur J Pharmacol 2017; 794:27-36.

51. Gupta M, Sharma P, Mazumder AG, Patial V, Singh D. Dwindling of cardio damaging effect of isoproterenol by Punica granatum L. peel extract involve activation of nitric oxide-mediated Nrf2/ARE signaling pathway and apoptosis inhibition. Nitric Oxide 2015; 50:105-113.

52. Sahu BD, Anubolu H, Koneru M, Kumar JM, Kuncha M, Rachamalla SS, et al. Cardioprotective effect of embelin on isoproterenol-induced myocardial injury in rats: possible involvement of mitochondrial dysfunction and apoptosis. Life Sci 2014; 107:59-67.

53. Chang JW, Hwang HS, Kim YS, Kim HJ, Shin YS, Jittreetat T, et al. Protective effect of Artemisia asiatica (Pamp.) Nakai ex Kitam ethanol extract against cisplatin-induced apoptosis of human HaCaT keratinocytes: Involvement of NF-kappa B- and Bcl-2-controlled mitochondrial signaling. Phytomedicine 2015; 22:679-688.

54. Yue C, Chen J, Hou R, Tian W, Liu K, Wang D, et al. The antioxidant action and mechanism of selenizing Schisandra chinensis polysaccharide in chicken embryo hepatocyte. Int J Biol Macromol 2017; 98:506-514.

55. Im GJ, Chang J, Lee S, Choi J, Jung HH, Lee HM, et al. Protective role of edaravone against cisplatin-induced ototoxicity in an auditory cell line. Hear Res 2015; 330:113-118.

56. Khan R, Khan AQ, Qamar W, Lateef A, Tahir M, Rehman MU, et al. Chrysin protects against cisplatin-induced colon. toxicity via amelioration of oxidative stress and apoptosis: probable role of p38MAPK and p53. Toxicol Appl Pharmacol 2012; 258:315-329.

57. Zhang W, Li Y, Ge Z. Cardiaprotective effect of crocetin by attenuating apoptosis in isoproterenol induced myocardial infarction rat model. Biomed Pharmacother 2017; 93:376-382.

58. Chakraborty S, Kaur S, Guha S, Batra SK. The multifaceted roles of neutrophil gelatinase associated lipocalin (NGAL) in inflammation and cancer. Biochim Biophys Acta 2012; 1826:129-169.

59. Palazzuoli A, Beltrami M, Pellegrini M, Nuti R. Natriuretic peptides and NGAL in heart failure: does a link exist? Clin Chim Acta 2012; 413:1832-1838.

60. Gouweleeuw L, Naude PJ, Rots M, DeJongste MJ, Eisel UL, Schoemaker RG. The role of neutrophil gelatinase associated lipocalin (NGAL) as biological constituent linking depression and cardiovascular disease. Brain Behav Immun 2015; 46:23-32.

61. Frogoudaki A, Andreou C, Parissis J, Maniotis C, Nikolaou M, Rizos I, et al. Clinical and prognostic implications of plasma NGAL and NT-proBNP in adult patients with congenital heart disease. Int J Cardiol 2014; 177:1026-1030.

62. Hamzic N, Blomqvist A, Nilsberth C. Immune-induced expression of lipocalin-2 in brain endothelial cells: relationship with interleukin-6, cyclooxygenase-2 and the febrile response. J Neuroendocrinol 2013; 25:271-280.

63. Eilenberg W, Stojkovic S, Piechota-Polanczyk A, Kaun C, Rauscher S, Groger M, et al. Neutrophil gelatinase-associated lipocalin (NGAL) is associated with symptomatic carotid atherosclerosis and drives pro-inflammatory state in vitro. Eur J Vasc Endovasc Surg 2016; 51:623-631.

64. Borkham-Kamphorst E, Drews F, Weiskirchen R. Induction of lipocalin-2 expression in acute and chronic experimental liver injury moderated by pro-inflammatory cytokines interleukin-1β through nuclear factor-κB activation. Liver Int 2011; 31:656-665.

65. Ethiraj P, Veerappan K, Samuel S, Sivapatham S. Interferon β improves the efficacy of low dose cisplatin by inhibiting NF-κB/p-Akt signaling on HeLa cells. Biomed Pharmacother 2016; 82:124-132.

66. Talwar H, Bauerfeld C, Bouhamdan M, Farshi P, Liu Y, Samavati L. MKP-1 negatively regulates LPS-mediated IL-1β production through p38 activation and HIF-1α expression. Cell Signal 2017; 34:1-10.

67. Rao Z, Wang S, Wang J. Peroxiredoxin 4 inhibits IL-1beta-induced chondrocyte apoptosis via PI3K/AKT signaling. Biomed Pharmacother 2017; 90:414-420.

68. Bueno-Silva B, Kawamoto D, Ando-Suguimoto ES, Casarin RCV, Alencar SM, Rosalen PL, et al. Brazilian red propolis effects on peritoneal macrophage activity: nitric oxide, cell viability, pro-inflammatory cytokines and gene expression. J Ethnopharmacol 2017.

69. Nojiri T, Hosoda H, Kimura T, Tokudome T, Miura K, Takabatake H, et al. Protective effects of ghrelin on cisplatin-induced nephrotoxicity in mice. Peptides 2016; 82:85-91.