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Published in: Cardiovascular Drugs and Therapy 4/2007

01-08-2007

Transforming Growth Factor and Nuclear Factor Kappa B Mediated Prophylactic Cardioprotection by Total Flavonoids of Fructus Chorspondiatis in Myocardial Ischemia

Authors: Jienan Ao, Huijuan Feng, Fang Xia

Published in: Cardiovascular Drugs and Therapy | Issue 4/2007

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Abstract

Background

Chorspomias axillaries Batt et Hill, a well-known Chinese herb, has been used in clinical treatment of angina pectoris for hundreds of years, but its effective components and intrinsic cardioprotective mechanism are still beyond us.

Objectives and methods

In this study, we extracted Total Flavonoids of Fructus Chorspondiatis (TFFC), a potential effective component from Chorspomias axillaries Batt et Hill to investigate its effect on myocardial ischemia induced by isoproteronol in rat and elucidated its probable mechanism.

Results

The results showed that prophylactically ``intragastrical administration of TFFC at the dose of 200 mg/kg body weight effectively suppressed the variation of J points in electrocardiogram (0.211 ± 0.059 mV versus 0.277 ± 0.046 mV, p < 0.05) and inhibited the upregulated serum level of creatine kinase (754 ± 114 U/l versus 1,112 ± 239 U/l, p < 0.05), creatine kinase -MB (700 ± 95 U/l versus 1,012 ± 252 U/l, p < 0.05) and lactate dehydrogenase (1,174 ± 200 U/l versus 2,025 ± 975 U/l, p < 0.05) in myocardial ischemia, revealing its cardioprotective effect. It increased a potent tissue protective polypeptide, transforming growth factor β1 (TGF-β1) level as well as its receptors TβRI and TβRII(p < 0.05) and significantly inhibited the expression of a redox-sensitive transcription factor, nuclear factor kappa B (NF-κB).

Conclusions

These data demonstrated that TFFC at the dose of 200 mg/kg body weight exerts prophylactically cardioprotective effect during ischemia injury. Part of its cardioprotective mechanism may relate to induction of TGF-β1 to competitively inhibit NF-κB signaling pathway. Prophylactically exogenous administration with the component may serve as a novel therapeutic strategy for ischemic cardiovascular diseases.
Literature
1.
go back to reference Akhtar M, Ordovas K, Martin A, Higins CB, Michaels AD. Effect of chronic sustained-release dipyridamole on myocardial blood flow and left ventricular function in patients with ischemic cardiomyopathy. Congest Heart 2007;13:130–35.CrossRef Akhtar M, Ordovas K, Martin A, Higins CB, Michaels AD. Effect of chronic sustained-release dipyridamole on myocardial blood flow and left ventricular function in patients with ischemic cardiomyopathy. Congest Heart 2007;13:130–35.CrossRef
2.
go back to reference Yeh MM, Larson AM, Campbell JS, Fausto N, Rulyak SJ, Swanson PE. The expression of transforming growth factor-alpha in cirrhosis, dysplastic nodules, and hepatocellular carcinoma: an immunohistochemical study of 70 cases. Am J Surg Pathol 2007;31:681–9.PubMedCrossRef Yeh MM, Larson AM, Campbell JS, Fausto N, Rulyak SJ, Swanson PE. The expression of transforming growth factor-alpha in cirrhosis, dysplastic nodules, and hepatocellular carcinoma: an immunohistochemical study of 70 cases. Am J Surg Pathol 2007;31:681–9.PubMedCrossRef
3.
go back to reference Gooch JL, Gorin Y, Zhang BX, Abboud HE. Involvement of calcineurin in transforming growth factor-beta-mediated regulation of extracellular matrix accumulation. J Biol Chem 2004;279:15561–70.PubMedCrossRef Gooch JL, Gorin Y, Zhang BX, Abboud HE. Involvement of calcineurin in transforming growth factor-beta-mediated regulation of extracellular matrix accumulation. J Biol Chem 2004;279:15561–70.PubMedCrossRef
4.
go back to reference Nakagawa T, Yamaguchi M. Overexpression of regucalcin suppresses cell response for tumor necrosis factor-alpha or transforming growth factor-beta 1 in cloned normal rat kidney proximal tubular epithelial NRK52E cells. J Cell Biochem 2007;100:1178–90.PubMedCrossRef Nakagawa T, Yamaguchi M. Overexpression of regucalcin suppresses cell response for tumor necrosis factor-alpha or transforming growth factor-beta 1 in cloned normal rat kidney proximal tubular epithelial NRK52E cells. J Cell Biochem 2007;100:1178–90.PubMedCrossRef
5.
go back to reference Prunier C, Howe PH. Disabled-2 (Dab2) is required for transforming growth factor beta-induced epithelial to mesenchymal transition (EMT). J Biol Chem 2005;280:17540–8.PubMedCrossRef Prunier C, Howe PH. Disabled-2 (Dab2) is required for transforming growth factor beta-induced epithelial to mesenchymal transition (EMT). J Biol Chem 2005;280:17540–8.PubMedCrossRef
6.
go back to reference De Filippis D, Russo A, De Stefano D, Maiuri MC, Esposito G, Cinelli MP, et al. Local administration of WIN 55,212-2 reduces chronic granuloma-associated angiogenesis in rat by inhibiting NF-kappaB activation. J Mol Med 2007;85:635–45.PubMedCrossRef De Filippis D, Russo A, De Stefano D, Maiuri MC, Esposito G, Cinelli MP, et al. Local administration of WIN 55,212-2 reduces chronic granuloma-associated angiogenesis in rat by inhibiting NF-kappaB activation. J Mol Med 2007;85:635–45.PubMedCrossRef
7.
go back to reference Liu X, Shen J, Jin Y, Duan M, Xu J. Recombinant human erythropoietin (rhEPO) preconditioning on nuclear factor-kappa B (NF-kB) activation & proinflammatory cytokines induced by myocardial ischaemia-reperfusion. Indian J Med Res 2006;124:343–54.PubMed Liu X, Shen J, Jin Y, Duan M, Xu J. Recombinant human erythropoietin (rhEPO) preconditioning on nuclear factor-kappa B (NF-kB) activation & proinflammatory cytokines induced by myocardial ischaemia-reperfusion. Indian J Med Res 2006;124:343–54.PubMed
8.
go back to reference Valen G, Yan ZQ, Hansson GK. Nuclear factor kappa-B and the heart. J Am Coll Cardiol 2001;38:307–14.PubMedCrossRef Valen G, Yan ZQ, Hansson GK. Nuclear factor kappa-B and the heart. J Am Coll Cardiol 2001;38:307–14.PubMedCrossRef
9.
go back to reference Ahn KS, Sethi G, Aggarwal BB. Simvastatin potentiates TNF-alpha-induced apoptosis through the down-regulation of NF-kappa B-dependent antiapoptotic gene products: Role of I kappa B alpha kinase and TGF-beta-activated kinase-1. Journal of Immunology 2007;178:2507–16, FEB 15. Ahn KS, Sethi G, Aggarwal BB. Simvastatin potentiates TNF-alpha-induced apoptosis through the down-regulation of NF-kappa B-dependent antiapoptotic gene products: Role of I kappa B alpha kinase and TGF-beta-activated kinase-1. Journal of Immunology 2007;178:2507–16, FEB 15.
10.
go back to reference Tedgui A, Mallat Z. Anti-inflammatory mechanisms in the vascular wall. Cir Res 2001;88:877. Tedgui A, Mallat Z. Anti-inflammatory mechanisms in the vascular wall. Cir Res 2001;88:877.
11.
go back to reference Yang YM, Qin JM, Xu JH, Zhou EF, Feng GQ, Bai YF, et al. Effect of total flavones of cheorospondias axillaries fructus on L-type Ca2+ current, transient outward K+ and intracellular free Ca2+ of ventricular myocytes in rats. Chin Pharmaco Bull 2004;20:784–8. Yang YM, Qin JM, Xu JH, Zhou EF, Feng GQ, Bai YF, et al. Effect of total flavones of cheorospondias axillaries fructus on L-type Ca2+ current, transient outward K+ and intracellular free Ca2+ of ventricular myocytes in rats. Chin Pharmaco Bull 2004;20:784–8.
12.
go back to reference Zhang X, Bao B, Wang Z, Na R, Sun F, Li B. Protective effect of total flavonoids of Fructus Choerospondiatis on adriamycin-induced rat cardiac peroxidation. Zhong Yao Cai 2001;24:185–7.PubMed Zhang X, Bao B, Wang Z, Na R, Sun F, Li B. Protective effect of total flavonoids of Fructus Choerospondiatis on adriamycin-induced rat cardiac peroxidation. Zhong Yao Cai 2001;24:185–7.PubMed
13.
go back to reference Veeravalli KK, Akula A, Kota MK. Nitric oxide- and prostaglandin-mediated cardioprotection by bradykinin in myocardial ischemia and reperfusion injury. Pol J Pharmacol 2003;55:1021–9.PubMed Veeravalli KK, Akula A, Kota MK. Nitric oxide- and prostaglandin-mediated cardioprotection by bradykinin in myocardial ischemia and reperfusion injury. Pol J Pharmacol 2003;55:1021–9.PubMed
14.
go back to reference Cui T, Schopfer FJ, Zhang JF, Chen K, Ichikawa T, Baker PR, et al. Nitrated Fatty Acids: Endogenous Anti-Inflammatory Signaling Mediators. J Biol Chem 2006;281:35686–98.PubMedCrossRef Cui T, Schopfer FJ, Zhang JF, Chen K, Ichikawa T, Baker PR, et al. Nitrated Fatty Acids: Endogenous Anti-Inflammatory Signaling Mediators. J Biol Chem 2006;281:35686–98.PubMedCrossRef
15.
go back to reference Mortazavi-Haghighat R, Taghipour-Khiabani K, David S, Kerrigan CL, Philip A. Rapid and dynamic regulation of TGF-β receptors on blood vessels and fibroblasts during ischemia-reperfusion injury. Am J Physiol Cell Physiol 2002;282:1161–9. Mortazavi-Haghighat R, Taghipour-Khiabani K, David S, Kerrigan CL, Philip A. Rapid and dynamic regulation of TGF-β receptors on blood vessels and fibroblasts during ischemia-reperfusion injury. Am J Physiol Cell Physiol 2002;282:1161–9.
16.
go back to reference Yang YM, Xu CY, Xu JH, Zhou CF, Feng GQ, Wang YM. Effect of total flavones from fructus of choerospondias Axillaris on the lever of cAMP and adenylate cyclase in the isolated rat heart. Chin J national med 2001;7:34–5. Yang YM, Xu CY, Xu JH, Zhou CF, Feng GQ, Wang YM. Effect of total flavones from fructus of choerospondias Axillaris on the lever of cAMP and adenylate cyclase in the isolated rat heart. Chin J national med 2001;7:34–5.
17.
go back to reference Chen HJ, Li D, Saldeen T, Mehta JL. TGF-β1 attenuates myocardial ischemia-reperfusion injury via inhibition of upregulation of MMP-1. Am J Physiol Heart Circ Physiol 2003;284:1612–7. Chen HJ, Li D, Saldeen T, Mehta JL. TGF-β1 attenuates myocardial ischemia-reperfusion injury via inhibition of upregulation of MMP-1. Am J Physiol Heart Circ Physiol 2003;284:1612–7.
18.
go back to reference Lefer AM, Tsao P, Aoki N, Palladino MA, Jr. Mediation of cardioprotection by transforming growth factor-β. Science 1990;249:61–4.PubMedCrossRef Lefer AM, Tsao P, Aoki N, Palladino MA, Jr. Mediation of cardioprotection by transforming growth factor-β. Science 1990;249:61–4.PubMedCrossRef
19.
go back to reference Mehta JL, Yang BC, Strates BS, Mehta P. Role of TGF-beta1 in platelet-mediated cardioprotection during ischemia-reperfusion in isolated rat hearts. Growth Factors 1999;16:179–90.PubMedCrossRef Mehta JL, Yang BC, Strates BS, Mehta P. Role of TGF-beta1 in platelet-mediated cardioprotection during ischemia-reperfusion in isolated rat hearts. Growth Factors 1999;16:179–90.PubMedCrossRef
20.
go back to reference Moses HL, Yang EY, Pietenpol JA. TGF-beta stimulation and inhibition of cell proliferation: new mechanistic insights. Cell 1990;63:245–7.PubMedCrossRef Moses HL, Yang EY, Pietenpol JA. TGF-beta stimulation and inhibition of cell proliferation: new mechanistic insights. Cell 1990;63:245–7.PubMedCrossRef
21.
go back to reference Wei XH, Zang Y, Wu CY, Xu JT, Xin WJ, Liu XG. Peri-sciatic administration of recombinant rat TNF-alpha induces mechanical allodynia via upregulation of TNF-alpha in dorsal root ganglia and in spinal dorsal horn: The role of NF-kappa B pathway. Exp Neurol 2007;205:471–84.PubMedCrossRef Wei XH, Zang Y, Wu CY, Xu JT, Xin WJ, Liu XG. Peri-sciatic administration of recombinant rat TNF-alpha induces mechanical allodynia via upregulation of TNF-alpha in dorsal root ganglia and in spinal dorsal horn: The role of NF-kappa B pathway. Exp Neurol 2007;205:471–84.PubMedCrossRef
22.
go back to reference Nakagawa T, Yamaguchi M. Overexpression of regucalcin suppresses cell response for tumor necrosis factor-alpha or transforming growth factor-beta 1 in cloned normal rat kidney proximal tubular epithelial NRK52E cells. Journal of Cellular Biochemistry 2007;100:1178–90.PubMedCrossRef Nakagawa T, Yamaguchi M. Overexpression of regucalcin suppresses cell response for tumor necrosis factor-alpha or transforming growth factor-beta 1 in cloned normal rat kidney proximal tubular epithelial NRK52E cells. Journal of Cellular Biochemistry 2007;100:1178–90.PubMedCrossRef
23.
go back to reference Sakuma M, Hatsushika K, Koyama K, Katoh R, Ando T, Watanabe Y, et al. TGF-beta type I receptor kinase inhibitor down-regulates rheumatoid synoviocytes and prevents the arthritis induced by type II collagen antibody. Int Immunol 2007;19:117–26.PubMedCrossRef Sakuma M, Hatsushika K, Koyama K, Katoh R, Ando T, Watanabe Y, et al. TGF-beta type I receptor kinase inhibitor down-regulates rheumatoid synoviocytes and prevents the arthritis induced by type II collagen antibody. Int Immunol 2007;19:117–26.PubMedCrossRef
24.
go back to reference Wang J, Guo LL, Wang YY. Study on combination components and effectiveness of Chinese traditional herbal formulas. Zhongguo Zhong Yao Za Zhi 2006;31:5–9, Jan.PubMed Wang J, Guo LL, Wang YY. Study on combination components and effectiveness of Chinese traditional herbal formulas. Zhongguo Zhong Yao Za Zhi 2006;31:5–9, Jan.PubMed
25.
26.
go back to reference Kwan TH, Tong MK, Leung KT, Lai CK, Poon WT, Chan YW, et al. Acute renal failure associated with prolonged intake of slimming pills containing anthraquinones. Hong Kong Medical Journal 2006;12:394–7.PubMed Kwan TH, Tong MK, Leung KT, Lai CK, Poon WT, Chan YW, et al. Acute renal failure associated with prolonged intake of slimming pills containing anthraquinones. Hong Kong Medical Journal 2006;12:394–7.PubMed
27.
go back to reference Zhang XY, Wu HF. NMR-based metabonomic study on the subacute toxicity of aristolochic acid in rats. Food Chem Toxicol 2006;44:1006–14.PubMedCrossRef Zhang XY, Wu HF. NMR-based metabonomic study on the subacute toxicity of aristolochic acid in rats. Food Chem Toxicol 2006;44:1006–14.PubMedCrossRef
Metadata
Title
Transforming Growth Factor and Nuclear Factor Kappa B Mediated Prophylactic Cardioprotection by Total Flavonoids of Fructus Chorspondiatis in Myocardial Ischemia
Authors
Jienan Ao
Huijuan Feng
Fang Xia
Publication date
01-08-2007
Publisher
Springer US
Published in
Cardiovascular Drugs and Therapy / Issue 4/2007
Print ISSN: 0920-3206
Electronic ISSN: 1573-7241
DOI
https://doi.org/10.1007/s10557-007-6042-2

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