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Published in: Cardiovascular Toxicology 2/2014

01-06-2014

Preventive Effect of Total Flavones of Choerospondias axillaries on Ischemia/Reperfusion-Induced Myocardial Infarction-Related MAPK Signaling Pathway

Authors: Chunmei Li, Jie He, Yonglin Gao, Yanli Xing, Jian Hou, Jingwei Tian

Published in: Cardiovascular Toxicology | Issue 2/2014

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Abstract

Choerospondias axillaris (Guangzao) is a medicinal plant used in Mongolia, and its fruit is commonly used for the treatment of cardiovascular diseases in clinic. The constituents responsible for this effect are always conceded to be the total flavonoids of C. axillaries (TFC). The present study was to evaluate the preventive effect of TFC on acute myocardial infarction induced by ischemia/reperfusion (I/R) in rats and the possible signaling pathway involved. The model of myocardial I/R was caused by occlusion of the left anterior descending coronary artery for 30 min followed by reperfusion for 2 h. Cardiac dysfunction, infarct size, pathologic histology and apoptosis were examined. Heart tissues were homogenized for biochemistry assays and Western blots analysis. The results indicated that pretreatment with TFC strongly improved cardiac function, obviously reduced heart pathologic lesion in I/R rat hearts. TFC also could protect the heart from I/R injury by increasing the levels of catalase, glutathione peroxidase and superoxide dismutase in heart homogenate, and decreasing that of malondialdehyde level. These beneficial effects were associated with the decrease in TUNEL-positive nuclear staining, Bax and caspase-3 levels, and the increase in Bcl-2 expression. Moreover, TFC counteracted the I/R-induced decreased activation of p38 mitogen-activated protein kinase (MAPK) and Jun N-terminal kinase. These data suggested that TFC improved I/R-induced myocardium impairment via anti-oxidative and anti-apoptotic activities, and this beneficial effects were intervened by MAPK signaling pathway.
Literature
1.
go back to reference Patrice, G., Edith, B., & Thierry, P. (2013). Evidence for antioxidants consumption in the coronary blood of patients with an acute myocardial infarction. Journal of Thrombosis and Thrombolysis, 35, 41–47.PubMedCrossRef Patrice, G., Edith, B., & Thierry, P. (2013). Evidence for antioxidants consumption in the coronary blood of patients with an acute myocardial infarction. Journal of Thrombosis and Thrombolysis, 35, 41–47.PubMedCrossRef
2.
go back to reference Fearon, I. M., & Faux, S. P. (2009). Oxidative stress and cardiovascular disease: novel tools give (free) radical insight. Journal of Molecular and Cellular Cardiology, 47, 372–381.PubMedCrossRef Fearon, I. M., & Faux, S. P. (2009). Oxidative stress and cardiovascular disease: novel tools give (free) radical insight. Journal of Molecular and Cellular Cardiology, 47, 372–381.PubMedCrossRef
3.
go back to reference Perrelli, M. G., Pagliaro, P., & Penna, C. (2011). Ischemia/reperfusion injury and cardioprotective mechanisms: role of mitochondria and reactive oxygen species. World Journal of Cardiology, 3, 186–200.PubMedCentralPubMedCrossRef Perrelli, M. G., Pagliaro, P., & Penna, C. (2011). Ischemia/reperfusion injury and cardioprotective mechanisms: role of mitochondria and reactive oxygen species. World Journal of Cardiology, 3, 186–200.PubMedCentralPubMedCrossRef
4.
go back to reference Burley, D. S., & Baxter, G. F. (2009). Pharmacological targets revealed by myocardial postconditioning. Current Opinion in Pharmacology, 2, 177–188.CrossRef Burley, D. S., & Baxter, G. F. (2009). Pharmacological targets revealed by myocardial postconditioning. Current Opinion in Pharmacology, 2, 177–188.CrossRef
5.
go back to reference Li, Z. M. (2009). The clinical research of Guangzao fufang capsule on Angina. Chinese Journal of Integrative Medicine on Cardio/cerebrovascular Disease, 12, 1387–1388. Li, Z. M. (2009). The clinical research of Guangzao fufang capsule on Angina. Chinese Journal of Integrative Medicine on Cardio/cerebrovascular Disease, 12, 1387–1388.
6.
go back to reference Jin, T. (2011). The clinical research of Guangzao fufang capsule on coronary disease. Chinese Journal of Ethnomedicine and Ethnopharmacy, 16, 12–14. Jin, T. (2011). The clinical research of Guangzao fufang capsule on coronary disease. Chinese Journal of Ethnomedicine and Ethnopharmacy, 16, 12–14.
7.
go back to reference Liga, Qihe, Eerdun, Hasi, & Mei, H. (2002). Clinical observation of San-Wei-Guang-Zao capsule on coronary heart disease. Journal of Medicine & Pharmacy of Chinese Minorities, 8, 17–18. Liga, Qihe, Eerdun, Hasi, & Mei, H. (2002). Clinical observation of San-Wei-Guang-Zao capsule on coronary heart disease. Journal of Medicine & Pharmacy of Chinese Minorities, 8, 17–18.
8.
go back to reference Meng, Q. C. (2012). The effect of Guang-Zao-Qi-Wei-Wan on Stable angina pectoris. Journal of Medicine & Pharmacy of Chinese Minorities, 5, 1–2. Meng, Q. C. (2012). The effect of Guang-Zao-Qi-Wei-Wan on Stable angina pectoris. Journal of Medicine & Pharmacy of Chinese Minorities, 5, 1–2.
9.
go back to reference Li, Z. M. (2009). Clinical research of Compound Guangzao capsule on coronary heart disease. Chinese Journal of Integrative Medicine on Cardio/Cerebrovascular Disease, 7, 1387–1388. Li, Z. M. (2009). Clinical research of Compound Guangzao capsule on coronary heart disease. Chinese Journal of Integrative Medicine on Cardio/Cerebrovascular Disease, 7, 1387–1388.
10.
go back to reference Wang, H., Gao, X. D., Zhou, G. C., Cai, L., & Yao, W. B. (2008). In vitro and in vivo antioxidant activity of aqueous extract from Choerospondias axillaris fruit. Food Chemistry, 106, 888–895.CrossRef Wang, H., Gao, X. D., Zhou, G. C., Cai, L., & Yao, W. B. (2008). In vitro and in vivo antioxidant activity of aqueous extract from Choerospondias axillaris fruit. Food Chemistry, 106, 888–895.CrossRef
11.
go back to reference Li, B., Tian, G., Lin, N. J., Jin, B., & Cui, S. L. (1998). Effects of total flavones of choerospondias axillaris (TFC) on thymocyte apoptosis and ADA activation of mice. Chinese Journal of Microbiology and Immunology, 5, 386–391. Li, B., Tian, G., Lin, N. J., Jin, B., & Cui, S. L. (1998). Effects of total flavones of choerospondias axillaris (TFC) on thymocyte apoptosis and ADA activation of mice. Chinese Journal of Microbiology and Immunology, 5, 386–391.
12.
go back to reference Ao, J., Feng, H., & Xia, F. (2007). Transforming growth factor and nuclear factor Kappa B mediated prophylactic cardioprotection by total flavonoids of fructus Chorspondiatis in myocardial ischemia. Cardiovascular Drugs and Therapy, 21, 235–241.PubMedCrossRef Ao, J., Feng, H., & Xia, F. (2007). Transforming growth factor and nuclear factor Kappa B mediated prophylactic cardioprotection by total flavonoids of fructus Chorspondiatis in myocardial ischemia. Cardiovascular Drugs and Therapy, 21, 235–241.PubMedCrossRef
13.
go back to reference Fan, H. Y., Sai, Y., Aodeng, G., & Song, T. (2005). Research on extracting process of flavonoids from Choerospondias axillaxi. Acta Scientiarum Naturalium Universitatis NeiMongol, 36, 81–83. Fan, H. Y., Sai, Y., Aodeng, G., & Song, T. (2005). Research on extracting process of flavonoids from Choerospondias axillaxi. Acta Scientiarum Naturalium Universitatis NeiMongol, 36, 81–83.
14.
go back to reference Zhu, J., Qiu, Y., Wang, Q., Zhu, Y., Hu, S., Zheng, L., et al. (2008). Low dose cyclophosphamide rescues myocardial function from ischemia-reperfusion in rats. European Journal of Cardio-Thoracic Surgery, 34, 661–666.PubMedCrossRef Zhu, J., Qiu, Y., Wang, Q., Zhu, Y., Hu, S., Zheng, L., et al. (2008). Low dose cyclophosphamide rescues myocardial function from ischemia-reperfusion in rats. European Journal of Cardio-Thoracic Surgery, 34, 661–666.PubMedCrossRef
15.
go back to reference Xu, X., Pacheco, B. D., Leng, L., Bucala, R., & Ren, J. (2013). Macrophage migration inhibitory factor plays a permissive role in the maintenance of cardiac contractile function under starvation through regulation of autophagy. Cardiovascular Research, 99, 412–421.PubMedCrossRef Xu, X., Pacheco, B. D., Leng, L., Bucala, R., & Ren, J. (2013). Macrophage migration inhibitory factor plays a permissive role in the maintenance of cardiac contractile function under starvation through regulation of autophagy. Cardiovascular Research, 99, 412–421.PubMedCrossRef
16.
go back to reference Betge, S., Lutz, K., Roskos, M., & Figulla, H. R. (2007). Oral treatment with probucol in a pharmacological dose has no beneficial effects on mortality in chronic ischemic heart failure after large myocardial infarction in rats. European Journal of Pharmacology, 558, 119–127.PubMedCrossRef Betge, S., Lutz, K., Roskos, M., & Figulla, H. R. (2007). Oral treatment with probucol in a pharmacological dose has no beneficial effects on mortality in chronic ischemic heart failure after large myocardial infarction in rats. European Journal of Pharmacology, 558, 119–127.PubMedCrossRef
17.
go back to reference Li, C., Gao, Y., Tian, J., Xing, Y., Zhu, H., & Shen, J. (2012). Long-term oral Asperosaponin VI attenuates cardiac dysfunction, myocardial fibrosis in a rat model of chronic myocardial infarction. Food Chemical Toxicology, 50, 1432–1438.PubMedCrossRef Li, C., Gao, Y., Tian, J., Xing, Y., Zhu, H., & Shen, J. (2012). Long-term oral Asperosaponin VI attenuates cardiac dysfunction, myocardial fibrosis in a rat model of chronic myocardial infarction. Food Chemical Toxicology, 50, 1432–1438.PubMedCrossRef
18.
go back to reference Panda, V. S., Suresh, R., & Naik, S. R. (2008). Cardioprotective activity of Ginkgo biloba phytosomes in isoproterenol-induced myocardial necrosis in rats: A biochemical and histoarchitectural evaluation. Experimental and Toxicologic Pathology, 60, 397–404.PubMedCrossRef Panda, V. S., Suresh, R., & Naik, S. R. (2008). Cardioprotective activity of Ginkgo biloba phytosomes in isoproterenol-induced myocardial necrosis in rats: A biochemical and histoarchitectural evaluation. Experimental and Toxicologic Pathology, 60, 397–404.PubMedCrossRef
19.
go back to reference Qin, F., Liu, Y. X., Zhao, H. W., Huang, X., Ren, P., & Zhu, Z. Y. (2009). Chinese medicinal formula Guan-Xin-Er-Hao protects the heart against oxidative stress induced by acute ischemic myocardial injury in rats. Phytomedicine, 16, 215–221.PubMedCrossRef Qin, F., Liu, Y. X., Zhao, H. W., Huang, X., Ren, P., & Zhu, Z. Y. (2009). Chinese medicinal formula Guan-Xin-Er-Hao protects the heart against oxidative stress induced by acute ischemic myocardial injury in rats. Phytomedicine, 16, 215–221.PubMedCrossRef
20.
go back to reference Misao, J., Hayakawa, Y., Ohno, M., Kato, S., Fujiwara, T., & Fujiwara, H. (1996). Expression of bcl-2 protein, an inhibitor of apoptosis, and Bax, an accelerator of apoptosis, in ventricular myocytes of human hearts with myocardial infarction. Circulation, 94, 1506–1512.PubMedCrossRef Misao, J., Hayakawa, Y., Ohno, M., Kato, S., Fujiwara, T., & Fujiwara, H. (1996). Expression of bcl-2 protein, an inhibitor of apoptosis, and Bax, an accelerator of apoptosis, in ventricular myocytes of human hearts with myocardial infarction. Circulation, 94, 1506–1512.PubMedCrossRef
21.
go back to reference Liu, S., Pereira, N. A., Teo, J. J., Miller, P., Shah, P., & Song, Z. (2007). Mitochondrially targeted Bcl-2 and Bcl-X(L) chimeras elicit different apoptotic responses. Molecules and Cells, 24, 378–387.PubMed Liu, S., Pereira, N. A., Teo, J. J., Miller, P., Shah, P., & Song, Z. (2007). Mitochondrially targeted Bcl-2 and Bcl-X(L) chimeras elicit different apoptotic responses. Molecules and Cells, 24, 378–387.PubMed
22.
go back to reference Shacka, J. J., & Roth, K. A. (2005). Regulation of neuronal cell death and neurodegeneration by members of the Bcl-2 family: therapeutic implications. Current Drug Targets-CNS Neurological Disorder, 4, 25–39.CrossRef Shacka, J. J., & Roth, K. A. (2005). Regulation of neuronal cell death and neurodegeneration by members of the Bcl-2 family: therapeutic implications. Current Drug Targets-CNS Neurological Disorder, 4, 25–39.CrossRef
23.
go back to reference Hong-Li, S., Lei, L., Lei, S., Dan, Z., De-Li, D., Guo-Fen, Q., et al. (2008). Cardioprotective effects and underlying mechanisms of oxymatrine against Ischemic myocardial injuries of rats. Phytotherapy Research, 22, 985–989.PubMedCrossRef Hong-Li, S., Lei, L., Lei, S., Dan, Z., De-Li, D., Guo-Fen, Q., et al. (2008). Cardioprotective effects and underlying mechanisms of oxymatrine against Ischemic myocardial injuries of rats. Phytotherapy Research, 22, 985–989.PubMedCrossRef
24.
go back to reference Guo, J., Li, H. Z., Wang, L. C., Zhang, W. H., Li, G. W., Xing, W. J., et al. (2012). Increased expression of calcium-sensing receptors in atherosclerosis confers hypersensitivity to acute myocardial infarction in rats. Molecular and Cellular Biochemistry, 366, 345–354.PubMedCrossRef Guo, J., Li, H. Z., Wang, L. C., Zhang, W. H., Li, G. W., Xing, W. J., et al. (2012). Increased expression of calcium-sensing receptors in atherosclerosis confers hypersensitivity to acute myocardial infarction in rats. Molecular and Cellular Biochemistry, 366, 345–354.PubMedCrossRef
25.
go back to reference Guo, J., Zhang, K., Ji, Y., Jiang, X., & Zuo, S. (2008). Effects of ethyl pyruvate on myocardial apoptosis and expression of Bcl-2 and Bax proteins after ischemia-reperfusion in rats. Journal of Huazhong University (Science Technolog Medicine Science), 28, 281–283.CrossRef Guo, J., Zhang, K., Ji, Y., Jiang, X., & Zuo, S. (2008). Effects of ethyl pyruvate on myocardial apoptosis and expression of Bcl-2 and Bax proteins after ischemia-reperfusion in rats. Journal of Huazhong University (Science Technolog Medicine Science), 28, 281–283.CrossRef
26.
go back to reference Nishikawa, S., Tatsumi, T., Shiraishi, J., Matsunaga, S., Takeda, M., Mano, A., et al. (2006). Nicorandil regulates Bcl-2 family proteins and protects cardiac myocytes against hypoxia induced apoptosis. Journal of Molecular and Cellular Cardiology, 40, 510–519.PubMedCrossRef Nishikawa, S., Tatsumi, T., Shiraishi, J., Matsunaga, S., Takeda, M., Mano, A., et al. (2006). Nicorandil regulates Bcl-2 family proteins and protects cardiac myocytes against hypoxia induced apoptosis. Journal of Molecular and Cellular Cardiology, 40, 510–519.PubMedCrossRef
27.
go back to reference Nicholson, D. W., Ali, A., Thornberry, N. A., Vaillancourt, J. P., Ding, C. K., Gallant, M., et al. (1995). Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature, 376, 37–43.PubMedCrossRef Nicholson, D. W., Ali, A., Thornberry, N. A., Vaillancourt, J. P., Ding, C. K., Gallant, M., et al. (1995). Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature, 376, 37–43.PubMedCrossRef
28.
go back to reference Liu, J., Mao, W., Ding, B., & Liang, C. S. (2008). ERKs/p53 signal transduction pathway is involved in doxorubicin-induced apoptosis in H9c2 cells and cardiomyocytes. American Journal of Physiology, 5, H1956–H1965. Liu, J., Mao, W., Ding, B., & Liang, C. S. (2008). ERKs/p53 signal transduction pathway is involved in doxorubicin-induced apoptosis in H9c2 cells and cardiomyocytes. American Journal of Physiology, 5, H1956–H1965.
29.
go back to reference Hsieh, C. C., & Papaconstantinou, J. (2006). Thioredoxin-ASK1 complex levels regulate ROS-mediated p38 MAPK pathway activity in livers of aged and long-lived snell dwarf mice. FASEB Journal, 2, 259–268.CrossRef Hsieh, C. C., & Papaconstantinou, J. (2006). Thioredoxin-ASK1 complex levels regulate ROS-mediated p38 MAPK pathway activity in livers of aged and long-lived snell dwarf mice. FASEB Journal, 2, 259–268.CrossRef
30.
go back to reference Engelbrecht, A. M., Engelbrecht, P., Genade, S., Niesler, C., Page, C., Smuts, M., et al. (2005). Long-chain polyunsaturated fatty acids protect the heart against ischemia/reperfusion-induced injury via a MAPK dependent pathway. Journal of Molecular and Cellular Cardiology, 39, 940–954.PubMedCrossRef Engelbrecht, A. M., Engelbrecht, P., Genade, S., Niesler, C., Page, C., Smuts, M., et al. (2005). Long-chain polyunsaturated fatty acids protect the heart against ischemia/reperfusion-induced injury via a MAPK dependent pathway. Journal of Molecular and Cellular Cardiology, 39, 940–954.PubMedCrossRef
31.
go back to reference Li, D. Y., Tao, L., Liu, H., Christopher, T. A., Lopez, B. L., & Ma, X. L. (2006). Role of ERK1/2 in the anti-apoptotic and cardioprotective effects of nitric oxide after myocardial ischemia and reperfusion. Apoptosis, 11, 923–930.PubMedCrossRef Li, D. Y., Tao, L., Liu, H., Christopher, T. A., Lopez, B. L., & Ma, X. L. (2006). Role of ERK1/2 in the anti-apoptotic and cardioprotective effects of nitric oxide after myocardial ischemia and reperfusion. Apoptosis, 11, 923–930.PubMedCrossRef
32.
go back to reference Shimada, K., Nakamura, M., Ishida, E., Kishi, M., & Konishi, N. (2003). Roles of p38- and c-jun NH2-terminal kinase-mediated pathways in 2-methoxyestradiol-induced p53 induction and apoptosis. Carcinogenesis, 6, 1067–1075.CrossRef Shimada, K., Nakamura, M., Ishida, E., Kishi, M., & Konishi, N. (2003). Roles of p38- and c-jun NH2-terminal kinase-mediated pathways in 2-methoxyestradiol-induced p53 induction and apoptosis. Carcinogenesis, 6, 1067–1075.CrossRef
Metadata
Title
Preventive Effect of Total Flavones of Choerospondias axillaries on Ischemia/Reperfusion-Induced Myocardial Infarction-Related MAPK Signaling Pathway
Authors
Chunmei Li
Jie He
Yonglin Gao
Yanli Xing
Jian Hou
Jingwei Tian
Publication date
01-06-2014
Publisher
Springer US
Published in
Cardiovascular Toxicology / Issue 2/2014
Print ISSN: 1530-7905
Electronic ISSN: 1559-0259
DOI
https://doi.org/10.1007/s12012-013-9238-7

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