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Published in: Cardiovascular Toxicology 3/2015

01-07-2015

Total Flavones of Choerospondias axillaris Attenuate Cardiac Dysfunction and Myocardial Interstitial Fibrosis by Modulating NF-κB Signaling Pathway

Authors: Bei Sun, Qiumei Xia, Zhiyong Gao

Published in: Cardiovascular Toxicology | Issue 3/2015

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Abstract

This study aimed to investigate the effect of total flavonoids of Choerospondias axillaris (TFC) on myocardial infarction (MI)-induced cardiac dysfunction, interstitial fibrosis and inflammatory reaction and further to clarify the potential signaling pathway involved. Rats were subjected to MI via coronary artery occlusion. The model establishment was confirmed by the occurrence of ST-segment elevation in electrocardiogram. Then, TFC was administrated at doses of 75, 150 and 300 mg/kg for 28 consecutive days (gavage). Body weight and heart weight were recorded. Hemodynamics, infarct size and myocardial fibrosis were examined. Blood samples were collected to determine tumor necrosis factor-α (TNF-α) and interleukin 6, 10 (IL-6, IL-10) levels. The expressions of matrix metalloproteinases-2, 9 (MMP-2, 9), phosphor-IKBα (p-IKBα) and transforming growth factor-β1 (TGF-β1) were assayed by Western blot. The results indicated that TFC significantly improved cardiac dysfunction, the heart coefficient and myocardial fibrosis in MI rat. TFC also decreased the levels of TNF-α and IL-6, but increased IL-10 content. Moreover, treatment with TFC protected the heart from chronic MI injury by decreasing the expressions of MMP-2, 9, TGF-β1 and p-IKBα. The results suggested that TFC attenuated cardiac dysfunction and myocardial interstitial fibrosis by modulating nuclear factor-kappa B (NF-κB) signaling pathway.
Literature
1.
go back to reference Li, C., Browder, W., & Kao, R. L. (1999). Early activation of transcription factor NF-kappaB during ischemia in perfused rat heart. American Journal of Physiology-Heart and Circulatory Physiology, 276, H543–H552. Li, C., Browder, W., & Kao, R. L. (1999). Early activation of transcription factor NF-kappaB during ischemia in perfused rat heart. American Journal of Physiology-Heart and Circulatory Physiology, 276, H543–H552.
2.
go back to reference Onai, Y., Suzuki, J., Maejima, Y., Haraguchi, G., Muto, S., Itai, A., & Isobe, M. (2007). Inhibition of NF-{kappa}B improves left ventricular remodeling and cardiac dysfunction after myocardial infarction. American Journal of Physiology-Heart and Circulatory Physiology, 292, H530–H538.PubMedCrossRef Onai, Y., Suzuki, J., Maejima, Y., Haraguchi, G., Muto, S., Itai, A., & Isobe, M. (2007). Inhibition of NF-{kappa}B improves left ventricular remodeling and cardiac dysfunction after myocardial infarction. American Journal of Physiology-Heart and Circulatory Physiology, 292, H530–H538.PubMedCrossRef
3.
go back to reference Timmers, L., van Keulen, J. K., Hoefer, I. E., Meijs, M. F., van Middelaar, B., den Ouden, K., et al. (2009). Targeted deletion of nuclear factor kappa B p50 enhances cardiac remodeling and dysfunction following myocardial infarction. Circulation Research, 104, 699–706.PubMedCrossRef Timmers, L., van Keulen, J. K., Hoefer, I. E., Meijs, M. F., van Middelaar, B., den Ouden, K., et al. (2009). Targeted deletion of nuclear factor kappa B p50 enhances cardiac remodeling and dysfunction following myocardial infarction. Circulation Research, 104, 699–706.PubMedCrossRef
4.
go back to reference Trescher, K., Bernecker, O., Fellner, B., Gyöngyösi, M., Krieger, S., Demartin, R., et al. (2004). Adenovirus-mediated overexpression of inhibitor kappa B-alpha attenuates postinfarct remodeling in the rat heart. European Journal of Cardio-thoracic Surgery, 26, 960–967.PubMedCrossRef Trescher, K., Bernecker, O., Fellner, B., Gyöngyösi, M., Krieger, S., Demartin, R., et al. (2004). Adenovirus-mediated overexpression of inhibitor kappa B-alpha attenuates postinfarct remodeling in the rat heart. European Journal of Cardio-thoracic Surgery, 26, 960–967.PubMedCrossRef
5.
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.
6.
go back to reference Li, D. L. (2009). The protecting effects and mechanisms of TFC on the myocardium during the acute myocardial infarction. Jilin, China: Jilin University Press. Li, D. L. (2009). The protecting effects and mechanisms of TFC on the myocardium during the acute myocardial infarction. Jilin, China: Jilin University Press.
7.
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
8.
go back to reference Yang, Y. M., Qin, J. M., Xu, J. H., Zhou, E. F., Feng, G. Q., & Bai, Y. F. (2004). Effect of total flavones of choerospondias axillaries fructus on L-type Ca2+ current, transient outward K+ and intracellular free Ca2+ of ventricular myocytes in rats. Chinese Pharmacology Bulletin, 20, 784–788. Yang, Y. M., Qin, J. M., Xu, J. H., Zhou, E. F., Feng, G. Q., & Bai, Y. F. (2004). Effect of total flavones of choerospondias axillaries fructus on L-type Ca2+ current, transient outward K+ and intracellular free Ca2+ of ventricular myocytes in rats. Chinese Pharmacology Bulletin, 20, 784–788.
9.
go back to reference Zhang, X., Bao, B., Wang, Z., Na, R., Sun, F., & Li, B. (2001). Protective effect of total flavonoids of fructus choerospondiatis on adriamycin-induced rat cardiac peroxidation. Zhong Yao Cai, 24, 185–187.PubMed Zhang, X., Bao, B., Wang, Z., Na, R., Sun, F., & Li, B. (2001). Protective effect of total flavonoids of fructus choerospondiatis on adriamycin-induced rat cardiac peroxidation. Zhong Yao Cai, 24, 185–187.PubMed
10.
go back to reference Li, C., He, J., Gao, Y., Xing, Y., Hou, J., & Tian, J. (2014). Preventive effect of total flavones of Choerospondias axillaries on ischemia/reperfusion-induced myocardial infarction-related MAPK signaling pathway. Cardiovascular Toxicology, 14, 145–152.PubMedCrossRef Li, C., He, J., Gao, Y., Xing, Y., Hou, J., & Tian, J. (2014). Preventive effect of total flavones of Choerospondias axillaries on ischemia/reperfusion-induced myocardial infarction-related MAPK signaling pathway. Cardiovascular Toxicology, 14, 145–152.PubMedCrossRef
11.
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
12.
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.
13.
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 and 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 and Chemical Toxicology, 50, 1432–1438.PubMedCrossRef
14.
go back to reference Agelaki, M. G., Pantos, C., Korantzopoulos, P., Tsalikakis, D. G., Baltogiannis, G. G., Fotopoulos, A., & Kolettis, T. M. (2007). Comparative antiarrhythmic efficacy of amiodarone and dronedarone during acute myocardial infarction in rats. European Journal of Pharmacology, 564, 150–157.PubMedCrossRef Agelaki, M. G., Pantos, C., Korantzopoulos, P., Tsalikakis, D. G., Baltogiannis, G. G., Fotopoulos, A., & Kolettis, T. M. (2007). Comparative antiarrhythmic efficacy of amiodarone and dronedarone during acute myocardial infarction in rats. European Journal of Pharmacology, 564, 150–157.PubMedCrossRef
15.
go back to reference Shibata, R., Izumiya, Y., Sato, K., Papanicolaou, K., Kihara, S., Colucci, W. S., et al. (2007). Adiponectin protects against the development of systolic dysfunction following myocardial infarction. Journal of Molecular and Cellular Cardiology, 42, 1065–1074.PubMedCentralPubMedCrossRef Shibata, R., Izumiya, Y., Sato, K., Papanicolaou, K., Kihara, S., Colucci, W. S., et al. (2007). Adiponectin protects against the development of systolic dysfunction following myocardial infarction. Journal of Molecular and Cellular Cardiology, 42, 1065–1074.PubMedCentralPubMedCrossRef
16.
go back to reference Wada, K., Fujimori, A., Matsukawa, U., Arai, Y., Sudoh, K., Yatsu, T., et al. (2005). Intravenous administration of conivaptan hydrochloride improves cardiac hemodynamics in rats with myocardial infarction-induced congestive heart failure. European Journal of Pharmacology, 507, 145–151.PubMedCrossRef Wada, K., Fujimori, A., Matsukawa, U., Arai, Y., Sudoh, K., Yatsu, T., et al. (2005). Intravenous administration of conivaptan hydrochloride improves cardiac hemodynamics in rats with myocardial infarction-induced congestive heart failure. European Journal of Pharmacology, 507, 145–151.PubMedCrossRef
17.
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.
18.
go back to reference Jankowska, E. A., Ponikowski, P., Piepoli, M. F., Banasiak, W., Anker, S. D., & Poole-Wilson, P. A. (2006). Autonomic imbalance and immune activation in chronic heart failure pathophysiological links. Cardiovascular Research, 70, 434–445.PubMedCrossRef Jankowska, E. A., Ponikowski, P., Piepoli, M. F., Banasiak, W., Anker, S. D., & Poole-Wilson, P. A. (2006). Autonomic imbalance and immune activation in chronic heart failure pathophysiological links. Cardiovascular Research, 70, 434–445.PubMedCrossRef
19.
go back to reference Gong, K. Z., Song, G., Spiers, J. P., Kelso, E. J., & Zhang, Z. G. (2007). Activation of immune and inflammatory systems in chronic heart failure: Novel therapeutic approaches. International Journal of Clinical Practice, 61, 611–621.PubMedCrossRef Gong, K. Z., Song, G., Spiers, J. P., Kelso, E. J., & Zhang, Z. G. (2007). Activation of immune and inflammatory systems in chronic heart failure: Novel therapeutic approaches. International Journal of Clinical Practice, 61, 611–621.PubMedCrossRef
20.
go back to reference Blum, A., & Miller, H. (2001). Pathophysiological role of cytokines in congestive heart failure. Annual Review of Medicine, 52, 15–27.PubMedCrossRef Blum, A., & Miller, H. (2001). Pathophysiological role of cytokines in congestive heart failure. Annual Review of Medicine, 52, 15–27.PubMedCrossRef
21.
go back to reference Valgimigli, M., Ceconi, C., Malagutti, P., Merli, E., Soukhomovskaia, O., Francolini, G., et al. (2005). Tumor necrosis factor-α receptor 1 is a major predictor of mortality and new-onset heart failure in patients with acute myocardial infarction: The cytokine-activation and long-term prognosis in myocardial infarction (C-ALPHA) study. Circulation, 111, 863–870.PubMedCrossRef Valgimigli, M., Ceconi, C., Malagutti, P., Merli, E., Soukhomovskaia, O., Francolini, G., et al. (2005). Tumor necrosis factor-α receptor 1 is a major predictor of mortality and new-onset heart failure in patients with acute myocardial infarction: The cytokine-activation and long-term prognosis in myocardial infarction (C-ALPHA) study. Circulation, 111, 863–870.PubMedCrossRef
22.
go back to reference Bolger, A. P., Sharma, R., von Haehling, S., Doehner, W., Oliver, B., Rauchhaus, M., et al. (2002). Effect of interleukin-10 on the production of tumor necrosis factoralpha by peripheral blood mononuclear cells from patients with chronic heart failure. American Journal of Cardiology, 90, 384–389.PubMedCrossRef Bolger, A. P., Sharma, R., von Haehling, S., Doehner, W., Oliver, B., Rauchhaus, M., et al. (2002). Effect of interleukin-10 on the production of tumor necrosis factoralpha by peripheral blood mononuclear cells from patients with chronic heart failure. American Journal of Cardiology, 90, 384–389.PubMedCrossRef
23.
go back to reference Chancey, A. L., Brower, G. L., Peterson, J. T., & Janicki, J. S. (2002). Effects of matrix metalloproteinase inhibition on ventricular remodeling due to volume overload. Circulation, 105, 1983–1988.PubMedCrossRef Chancey, A. L., Brower, G. L., Peterson, J. T., & Janicki, J. S. (2002). Effects of matrix metalloproteinase inhibition on ventricular remodeling due to volume overload. Circulation, 105, 1983–1988.PubMedCrossRef
24.
go back to reference Yasuda, S., Miyazaki, S., Kinoshita, H., Nagaya, N., Kanda, M., Goto, Y., & Nonogi, H. (2007). Enhanced cardiac production of matrix metalloproteinase-2 and -9 and its attenuation associated with pravastatin treatment in patients with acute myocardial infarction. Clinical Science (London), 112, 43–49.CrossRef Yasuda, S., Miyazaki, S., Kinoshita, H., Nagaya, N., Kanda, M., Goto, Y., & Nonogi, H. (2007). Enhanced cardiac production of matrix metalloproteinase-2 and -9 and its attenuation associated with pravastatin treatment in patients with acute myocardial infarction. Clinical Science (London), 112, 43–49.CrossRef
25.
go back to reference Gu, Y., Wang, X., Wang, X., Yuan, M., Wu, G., Hu, J., et al. (2012). Artemisinin attenuates post-infarct myocardial remodeling by down-regulating the NF-κB pathway. Tohoku Journal of Experimental Medicine, 227, 161–170.PubMedCrossRef Gu, Y., Wang, X., Wang, X., Yuan, M., Wu, G., Hu, J., et al. (2012). Artemisinin attenuates post-infarct myocardial remodeling by down-regulating the NF-κB pathway. Tohoku Journal of Experimental Medicine, 227, 161–170.PubMedCrossRef
Metadata
Title
Total Flavones of Choerospondias axillaris Attenuate Cardiac Dysfunction and Myocardial Interstitial Fibrosis by Modulating NF-κB Signaling Pathway
Authors
Bei Sun
Qiumei Xia
Zhiyong Gao
Publication date
01-07-2015
Publisher
Springer US
Published in
Cardiovascular Toxicology / Issue 3/2015
Print ISSN: 1530-7905
Electronic ISSN: 1559-0259
DOI
https://doi.org/10.1007/s12012-014-9298-3

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