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Effects of Xinjierkang on Nrf2/HO-1 expression in viral myocarditis mice models
Corresponding Author(s) : Weidong Yao
Cellular and Molecular Biology,
Vol. 66 No. 5: Issue 5
Abstract
In this study, the changes of Nrf2/HO-1 and cytokines TNF-α, IL-6, IL-17 and IL-1β in cardiac muscle cells of Viral myocarditis (VMC) mice were detected in order to clarify the mechanism of action of Xinjierkang (XJEK). One hundred and fifty healthy male BALBC mice were randomly divided into the normal group, model group, low-, medium- and high-dose XJEK groups, with 30 in each group. Replication of the VMC model in mice inoculated with CVB3m. Serum inflammatory factors TNF-α, IL-6, IL-17 and IL-1β, Nrf2 and HO-1 protein levels in myocardial tissue were compared. The results showed that no apoptotic cells were found in the myocardium of normal mice. The percentage of cardiomyocyte apoptosis in the low, medium and high dose groups of XJEK was significantly lower than the model group (P <0.05). At 3, 7, 14, 21, and 28 days after inoculation, compared with the normal group, the TNF-α, IL-6, IL-17 and IL-1β levels in the model group significantly increased (p < 0.05). After the administration of XJEK, compared with the model group, the TNF-α, IL-6, IL-17, and IL-1β levels in the low-, middle-, and high-dose XJEK groups significantly decreased (p < 0.05). At 28 days after inoculation, compared with the normal group, the expressions of Nrf2 and HO-1 proteins in the myocardial tissue of the model group were significantly down-regulated (p < 0.05); and compared with the model group, the expressions of Nrf2 and HO-1 proteins in the low-, medium-, and high-dose XJEK groups were significantly up-regulated (p < 0.05) in a concentration-dependent manner. In conclusion, XJEK can prevent myocardial injury in VMC mice, and its mechanism of action may be related to improving myocardial cell apoptosis, inhibiting inflammatory response, and up-regulating the expression of Nrf2 and HO-1 proteins in myocardial tissue.
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- Honghui Yang, Yan Chen, Chuanyu Gao.Interleukin-13 reduces cardiac injury and prevents heart dysfunction in viral myocarditis via enhanced M2 macrophage polarization. Oncotarget 2017; 8(59): 99495–99503.
- An B, Liu X, Li G, Yuan H. Interleukin-37 Ameliorates Coxsackievirus B3-induced Viral Myocarditis by Modulating the Th17/Regulatory T cell Immune Response. J Cardiovasc Pharmacol. 2017; 69(5):305-313.
- Riabi S, Gaaloul I, Harrath R, Aouni M.Persistent infection of human intestinal Caco-2 cell line by Coxsackieviruses B. Pathol Biol (Paris) 2012; 60(6):347-51.
- Cao Y, Xu X, Zhang P.Advances in the Traditional Chinese Medicine-Based Management of Viral Myocarditis.Cell Biochem Biophys 2015; 73(1):237-43.
- Cui S, Chen XL, Jiang MX.Study on pathological rhythm of traditional Chinese medicine about circadian distribution of premature ventricular contractions in 240 patients with viral myocarditis.Zhong Xi Yi Jie He Xue Bao 2005; 3(5):355-8.
- Wang QM, Chen GL, Wang YJ, Wang HS, Gao MH, Gong YZ.An experimental study on inhibitory effect of xinjierkang granules on virus myocarditis.Zhongguo Zhong Yao Za Zhi 2000; 25(5):293-6.
- Hu J, Zhang YX, Wang L, Ding L, Huang GY, Cai GW, Gao S. Protective effects of Xinji'erkang on myocardial infarction induced cardiac injury in mice. BMC Complement Altern Med 2017; 17(1):338.
- Wang G, Li L, Yu Y, Tu Y, Tong J, Zhang C, Liu Y, Li Y, Han Z, Jiang C, Wang S, Zhou EM, He X, Cai X.Highly pathogenic porcine reproductive and respiratory syndrome virus infection and induction of apoptosis in bone marrow cells of infected piglets. J Gen Virol 2016; 97(6):1356-1361.
- Kim JY, Bae BN, Kang G, Kim HJ, Park K.Cytokine expression associated with Helicobacter pylori and Epstein-Barr virus infection in gastric carcinogenesis. APMIS 2017; 125(9): 808-815.
- Pirhonen J, Sareneva T, Kurimoto M, Julkunen I, Matikainen S.Virus infection activates IL-1 beta and IL-18 production in human macrophages by a caspase-1-dependent pathway. J Immunol 1999; 162(12):7322-9.
- Yoruk U, Yaykasli KO, Ozhan H, Aslantas Y, Karabacak A, Basar C, Kaya E, Bulur S, Memisogulları R. Association of omentin Val109Asp polymorphism with coronary artery disease, Anatol J Cardiol 2014; 14(6):511-514.
- Ai F, Zheng J, Zhang Y, Fan T. Inhibition of 12/15-LO ameliorates CVB3-induced myocarditis by activating Nrf2. Chem Biol Interact 2017; 272:65-71.
- Song F, Kong F, Zhang H, Zhou Y, Li M.Ulinastatin Protects against CVB3-Induced Acute Viral Myocarditis through Nrf2 Activation. Inflammation 2018; 41(3):803-810.
- Gongliang Guo, Liqun Sun, Lili Yang, Haiming Xu. IDO1 depletion induces an anti-inflammatory response in macrophages in mice with chronic viral myocarditis. Cell cycle (Georgetown, Tex.) 2019; 18(416): 1-16.
- Yongzhan Bao, Cui Jing, Wanyu Shi.Effects of Chinese Herbal Recipes on Immunity in Immunosuppressive Mice.Afr J Tradit Complement Altern Med 2012; 9(4): 548–552.
- Zhu J, Zhang Y, Fan F, Wu G, Xiao Z, Zhou H. Tumor necrosis factor-α-induced protein 8-like-2 is involved in the activation of macrophages by Astragalus polysaccharides in vitro. Mol Med Rep 2018; 17(5):7428-7434.
- Xie ZC, Qian ZK, Liu ZW.Effect of ginseng on antiperoxidate injury in myocardium and erythrocytes in streptozocin-induced diabetic rats.Zhongguo Zhong Xi Yi Jie He Za Zhi 1993; 13(5):289-290.
- Krylova NV, Besednova NN, Solov'eva TF, Loenko IuN, Faustov VS, Konstantinova NA, Smolina TP, Eliakov GB.Anti-inflammatory effect of polysaccharide obtained from ginseng cell cultures.Antibiot Khimioter 1990; 35(4):41-2.
- Zhou Y, Wu Y, Deng L, Chen L, Zhao D, Lv L, Chen X, Man J, Wang Y, Shan H, Lu Y. The alkaloid matrine of the root of Sophora flavescens prevents arrhythmogenic effect of ouabain. Phytomedicine 2014; 21(7): 931-5.
- Dai S, Chan MY, Lee SS, Ogle CW.The antiarrhythmic effects of Sophora flavescens Ait. in rats and mice.Am J Chin Med 1986; 14(3-4):119-23.
- Fang Ye, Xiaoyi Li, Lili Li, Jing Yuan, Jun Chen.t-BHQ Provides Protection against Lead Neurotoxicity via Nrf2/HO-1 Pathway. Oxid Med Cell Longev 2016: 2075915.
- Shen X, Hu B, Xu G, Chen F, Ma R, Zhang N, Liu J, Ma X, Zhu J, Wu Y, Shen R.Activation of Nrf2/HO-1 Pathway by Glycogen Synthase Kinase-3β Inhibition Attenuates Renal Ischemia/Reperfusion Injury in Diabetic Rats. Kidney Blood Press Res 2017; 42(2):369-378.
- Kumar M, Thakur R. Syzygium cumini Seed Extract Ameliorates Arsenic-Induced Blood Cell Genotoxicity and Hepatotoxicity in Wistar Albino Rats. Rep Biochem Mol Biol 2018;7(1):110"118.
- Cheraghi M, Ahmadvand H, Maleki A, Babaeenezhad E, Shakiba S, Hassanzadeh F. Oxidative Stress Status and Liver Markers in Coronary Heart Disease. Rep Biochem Mol Biol 2019; 8(1):49-55.
- Bordbar M, Darvishzadeh R, Pazhouhandeh M, Kahrizi D. An overview of genome editing methods based on endonucleases. Modern Genetics J 2020; 15(2): 75-92.
References
Honghui Yang, Yan Chen, Chuanyu Gao.Interleukin-13 reduces cardiac injury and prevents heart dysfunction in viral myocarditis via enhanced M2 macrophage polarization. Oncotarget 2017; 8(59): 99495–99503.
An B, Liu X, Li G, Yuan H. Interleukin-37 Ameliorates Coxsackievirus B3-induced Viral Myocarditis by Modulating the Th17/Regulatory T cell Immune Response. J Cardiovasc Pharmacol. 2017; 69(5):305-313.
Riabi S, Gaaloul I, Harrath R, Aouni M.Persistent infection of human intestinal Caco-2 cell line by Coxsackieviruses B. Pathol Biol (Paris) 2012; 60(6):347-51.
Cao Y, Xu X, Zhang P.Advances in the Traditional Chinese Medicine-Based Management of Viral Myocarditis.Cell Biochem Biophys 2015; 73(1):237-43.
Cui S, Chen XL, Jiang MX.Study on pathological rhythm of traditional Chinese medicine about circadian distribution of premature ventricular contractions in 240 patients with viral myocarditis.Zhong Xi Yi Jie He Xue Bao 2005; 3(5):355-8.
Wang QM, Chen GL, Wang YJ, Wang HS, Gao MH, Gong YZ.An experimental study on inhibitory effect of xinjierkang granules on virus myocarditis.Zhongguo Zhong Yao Za Zhi 2000; 25(5):293-6.
Hu J, Zhang YX, Wang L, Ding L, Huang GY, Cai GW, Gao S. Protective effects of Xinji'erkang on myocardial infarction induced cardiac injury in mice. BMC Complement Altern Med 2017; 17(1):338.
Wang G, Li L, Yu Y, Tu Y, Tong J, Zhang C, Liu Y, Li Y, Han Z, Jiang C, Wang S, Zhou EM, He X, Cai X.Highly pathogenic porcine reproductive and respiratory syndrome virus infection and induction of apoptosis in bone marrow cells of infected piglets. J Gen Virol 2016; 97(6):1356-1361.
Kim JY, Bae BN, Kang G, Kim HJ, Park K.Cytokine expression associated with Helicobacter pylori and Epstein-Barr virus infection in gastric carcinogenesis. APMIS 2017; 125(9): 808-815.
Pirhonen J, Sareneva T, Kurimoto M, Julkunen I, Matikainen S.Virus infection activates IL-1 beta and IL-18 production in human macrophages by a caspase-1-dependent pathway. J Immunol 1999; 162(12):7322-9.
Yoruk U, Yaykasli KO, Ozhan H, Aslantas Y, Karabacak A, Basar C, Kaya E, Bulur S, Memisogulları R. Association of omentin Val109Asp polymorphism with coronary artery disease, Anatol J Cardiol 2014; 14(6):511-514.
Ai F, Zheng J, Zhang Y, Fan T. Inhibition of 12/15-LO ameliorates CVB3-induced myocarditis by activating Nrf2. Chem Biol Interact 2017; 272:65-71.
Song F, Kong F, Zhang H, Zhou Y, Li M.Ulinastatin Protects against CVB3-Induced Acute Viral Myocarditis through Nrf2 Activation. Inflammation 2018; 41(3):803-810.
Gongliang Guo, Liqun Sun, Lili Yang, Haiming Xu. IDO1 depletion induces an anti-inflammatory response in macrophages in mice with chronic viral myocarditis. Cell cycle (Georgetown, Tex.) 2019; 18(416): 1-16.
Yongzhan Bao, Cui Jing, Wanyu Shi.Effects of Chinese Herbal Recipes on Immunity in Immunosuppressive Mice.Afr J Tradit Complement Altern Med 2012; 9(4): 548–552.
Zhu J, Zhang Y, Fan F, Wu G, Xiao Z, Zhou H. Tumor necrosis factor-α-induced protein 8-like-2 is involved in the activation of macrophages by Astragalus polysaccharides in vitro. Mol Med Rep 2018; 17(5):7428-7434.
Xie ZC, Qian ZK, Liu ZW.Effect of ginseng on antiperoxidate injury in myocardium and erythrocytes in streptozocin-induced diabetic rats.Zhongguo Zhong Xi Yi Jie He Za Zhi 1993; 13(5):289-290.
Krylova NV, Besednova NN, Solov'eva TF, Loenko IuN, Faustov VS, Konstantinova NA, Smolina TP, Eliakov GB.Anti-inflammatory effect of polysaccharide obtained from ginseng cell cultures.Antibiot Khimioter 1990; 35(4):41-2.
Zhou Y, Wu Y, Deng L, Chen L, Zhao D, Lv L, Chen X, Man J, Wang Y, Shan H, Lu Y. The alkaloid matrine of the root of Sophora flavescens prevents arrhythmogenic effect of ouabain. Phytomedicine 2014; 21(7): 931-5.
Dai S, Chan MY, Lee SS, Ogle CW.The antiarrhythmic effects of Sophora flavescens Ait. in rats and mice.Am J Chin Med 1986; 14(3-4):119-23.
Fang Ye, Xiaoyi Li, Lili Li, Jing Yuan, Jun Chen.t-BHQ Provides Protection against Lead Neurotoxicity via Nrf2/HO-1 Pathway. Oxid Med Cell Longev 2016: 2075915.
Shen X, Hu B, Xu G, Chen F, Ma R, Zhang N, Liu J, Ma X, Zhu J, Wu Y, Shen R.Activation of Nrf2/HO-1 Pathway by Glycogen Synthase Kinase-3β Inhibition Attenuates Renal Ischemia/Reperfusion Injury in Diabetic Rats. Kidney Blood Press Res 2017; 42(2):369-378.
Kumar M, Thakur R. Syzygium cumini Seed Extract Ameliorates Arsenic-Induced Blood Cell Genotoxicity and Hepatotoxicity in Wistar Albino Rats. Rep Biochem Mol Biol 2018;7(1):110"118.
Cheraghi M, Ahmadvand H, Maleki A, Babaeenezhad E, Shakiba S, Hassanzadeh F. Oxidative Stress Status and Liver Markers in Coronary Heart Disease. Rep Biochem Mol Biol 2019; 8(1):49-55.
Bordbar M, Darvishzadeh R, Pazhouhandeh M, Kahrizi D. An overview of genome editing methods based on endonucleases. Modern Genetics J 2020; 15(2): 75-92.