Protective Effect of Combined Metoprolol and Atractylenolide I in Rats with Acute Myocardial Infarction via Modulation of the SIRT3/β-CATENIN/PPAR-γ Signaling Pathway Article

Authors

  • Weijian Zhou Liaocheng People’s Hospital, Liaocheng, Shandong, China
  • Jing Liu Yantai Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong, China
  • Zhongli Sun Liaocheng People’s Hospital, Liaocheng, Shandong, China
  • Yongpeng Dong Binzhou Hospital of Traditional Chinese Medicine, Binzhou, Shandong, China
  • Meiming Zhu Weiji Town Health Center, Binzhou, Shandong, China
  • Li Li Zibo Central Hospital, Zibo, Shandong, China https://orcid.org/0000-0002-5468-6875

DOI:

https://doi.org/10.1590/s2175-97902023e21639

Keywords:

Acute myocardial infarction, Metoprolol, Atractylenolide I, SIRT3/β-Catenin/PPAR-γ pathway

Abstract

Herein, we examined the protective effect of metoprolol combined with atractylenolide I (Atr I) in acute myocardial infarction (AMI) by regulating the SIRT3 (silent information regulator 3)/β-catenin/peroxisome proliferator-activated receptor gamma (PPAR-γ) signaling pathway. Briefly, 50 rats were randomly divided into the sham operation, model, metoprolol, Atr I, and combination metoprolol with Atr I groups (combined treatment group). The AMI model was established by ligating the left anterior descending coronary artery. After treatment, infarct size, histopathological changes, and cell apoptosis were examined using 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin staining, and the TUNEL assay. The left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), and left ventricular mass index (LVMI) were detected by echocardiography. Endothelin-1 (ET-1), nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) levels were detected using enzyme-linked immunosorbent assays. Furthermore, we measured lactate dehydrogenase (LDH), creatine kinase (CK) isoenzyme (CK-MB), and CK levels. Western blotting was performed to determine the expression of SIRT3, β-catenin, and PPAR-γ. Herein, the combined treatment group exhibited increased levels of LVEF, LVFS, and NO, whereas LVMI, ET-1, TNF-α, IL-6, LDH, CK-MB, and CK levels were decreased. Importantly, the underlying mechanism may afford protection against AMI by increasing the expression levels of SIRT3, β-catenin, and PPAR-γ.

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Author Biography

  • Zhongli Sun, Liaocheng People’s Hospital, Liaocheng, Shandong, China



References

Abel AAI, Clark AL. Long-term pharmacological management of reduced ejection fraction following acute myocardial infarction: Current status and future prospects. Int J Gen Med 2021;14:7797-805.

Albrecht-Schgoer K, Schgoer W, Holfeld J, Theurl M, Wiedemann D, Steger C, et al. The angiogenic factor secretoneurin induces coronary angiogenesis in a model of myocardial infarction by stimulation of vascular endothelial growth factor signaling in endothelial cells. Circulation 2012;126(21):2491-501.

Bosco E, Hsueh L, McConeghy KW, Gravenstein S, Saade E. Major adverse cardiovascular event definitions used in observational analysis of administrative databases: a systematic review. BMC Med Res Methodol 2021;21(1):241.

Chen W, Spitzl A, Mathes D, Nikolaev VO, Werner F, Weirather J, et al. Endothelial actions of ANP enhance myocardial inflammatory infiltration in the early phase after acute infarction. Circ Res 2016;119(2):237-48.

Chen Y, Tang XF, Gao RL, Yang YJ, Xu B, Yuan JQ. Association of β-Blocker therapy at discharge with clinical outcomes after acute coronary syndrome in patients without heart failure. Cardiovasc Ther 2020;2020:4351469.

Clemente-Moragón A, Gómez M, Villena-Gutiérrez R, Lalama DV, García-Prieto J, Martínez F, et al. Metoprolol exerts a non-class effect against ischaemia-reperfusion injury by abrogating exacerbated inflammation. Eur Heart J 2020;41(46):4425-40.

Deng M, Chen H, Long J, Song J, Xie L, Li X. Atractylenolides (I, II, and III): a review of their pharmacology and pharmacokinetics. Arch Pharm Res 2021;44(7):633-54.

DiNicolantonio JJ, Fares H, Niazi AK, Chatterjee S, D’Ascenzo F, Cerrato E, et al. β-Blockers in hypertension, diabetes, heart failure and acute myocardial infarction: a review of the literature. Open Heart 2015;2(1):e000230.

Fei L, Zhang J, Niu H, Yuan C, Ma X. Effects of Rosuvastatin and MiR-126 on myocardial injury induced by acute myocardial infarction in rats: Role of vascular endothelial growth factor A (VEGF-A). Med Sci Monit 2016;22:2324-34.

Gao L, Lu D, Xia G, Zhang H. The relationship between arterial stiffness index and coronary heart disease and its severity. BMC Cardiovasc Disord 2021;21(1):527.

Gheini A, Pooria A, Pourya A. Evaluating mortality rate and associated parameters in patients with acute coronary syndrome. Cardiovasc Hematol Disord Drug Targets 2020;20(3):221-6.

Hou J, Chen Y, Ma D, Wang C, Jin H, An Y, et al. [Effect of chronic emotional stress induced by empty bottle stimulation on inflammatory factors in rats with acute myocardial infarction: analysis of the CXCL12/CXCR4 axis]. Nan Fang Yi Ke Da Xue Xue Bao 2020;40(5):624-31.

Ishikura K, Nakagawa Y, Nakagawa Y, Tsuchiya A, Noda T, Takayama H, et al. The evaluation of helicopter emergency medical services with a physician for acute myocardial infarction in japan: a registry-based study of prognosis and time reduction. Air Med J 2021;40(6):399-403.

Ji G, Chen R, Zheng J. Atractylenolide I inhibits lipopolysaccharide-induced inflammatory responses via mitogen-activated protein kinase pathways in RAW264.7 cells. Immunopharmacol Immunotoxicol 2014;36(6):420-5.

Lee S, Jeon YM, Jo M, Kim HJ. Overexpression of SIRT3 suppresses oxidative stress-induced neurotoxicity and mitochondrial dysfunction in dopaminergic neuronal cells. Exp Neurobiol 2021;30(5):341-55.

Li X, Yan B. Research on the effect of cytokine concentration on the immune level and survival conditions of elderly patients with sepsis. Exp Ther Med 2018;16(2):842-6.

Li Z, Zhu S, Liu Q, Wei J, Jin Y, Wang X, et al. Polystyrene microplastics cause cardiac fibrosis by activating Wnt/β-catenin signaling pathway and promoting cardiomyocyte apoptosis in rats. Environ Pollut 2020;265(Pt A):115025.

Lin B, Feng D, Xu J. Cardioprotective effects of microRNA-18a on acute myocardial infarction by promoting cardiomyocyte autophagy and suppressing cellular senescence via brain derived neurotrophic factor. Cell Biosci 2019;9:38.

Lin B, Zheng W, Jiang X. Crosstalk between Circulatory Microenvironment and vascular endothelial cells in acute myocardial infarction. J Inflamm Res 2021;14:5597-610.

Liu J, Sun G, He Y, Song F, Chen S, Guo Z, et al. Early β-blockers administration might be associated with a reduced risk of contrast-induced acute kidney injury in patients with acute myocardial infarction. J Thorac Dis 2019;11(4):1589-96.

Liu ZF, Hu WW, Li R, Gao Y, Yan LL, Su N. Expression of lncRNA-ANRIL in patients with coronary heart disease before and after treatment and its short-term prognosis predictive value. Eur Rev Med Pharmacol Sci 2020;24(1):376-84.

Lv D, Luo M, Cheng Z, Wang R, Yang X, Guo Y, et al. Tubeimoside i ameliorates myocardial ischemia-reperfusion injury through sirt3-dependent regulation of oxidative stress and apoptosis. Oxid Med Cell Longev 2021;2021:5577019.

Ma J, Li ZY, Liang XP, Guo CX, Lu PP, Ma LH. Xinfuli granule improves post-myocardial infarction ventricular remodeling and myocardial fibrosis in rats by regulating TGF-β/Smads signaling pathway. J Geriatr Cardiol 2017;14(5):301-7.

Maghbooli Z, Emamgholipour S, Aliakbar S, Amini M, Gorgani-Firuzjaee S, Hossein-Nezhad A. Differential expressions of SIRT1, SIRT3, and SIRT4 in peripheral blood mononuclear cells from patients with type 2 diabetic retinopathy. Arch Physiol Biochem 2020;126(4):363-8.

Meng Z, Zhao Y, Zheng X, He Y. The relationship between AKI in patients with STEMI and Short-Term mortality: A propensity score matching analysis. Angiology 2021;72(8):733-9.

Metwalli O, Hashem E, Ajabnoor MA, Sr., Alama N, Banjar ZM. Study of some inflammatory mediators in the serum of patients with atherosclerosis and acute myocardial infarction. Cureus 2021;13(10):e18450.

Mohamed Kamel GA. Vinpocetine attenuates fluoxetine-induced liver damage in rats; Role of Nrf2 and PPAR-γ. Hum Exp Toxicol 2021;40(12 suppl):S509-18.

More S, Choi DK. Neuroprotective role of Atractylenolide-I in an In Vitro and In Vivo Model of Parkinson’s Disease. Nutrients 2017;9(5):451.

Norhayati MN, Shaiful Bahari I, Zaharah S, Nik Hazlina NH, Mohammad Aimanazrul Z, Irfan M. Metoprolol for prophylaxis of postoperative atrial fibrillation in cardiac surgery patients: systematic review and meta-analysis. BMJ Open 2020;10(10):e038364.

Paciello F, Pisani A, Rolesi R, Escarrat V, Galli J, Paludetti G, et al. Noise-Induced cochlear damage involves PPAR Down-Regulation through the Interplay between oxidative stress and inflammation. Antioxidants (Basel) 2021;10(8):1188.

Paget MB, Murray HE, Bailey CJ, Flatt PR, Downing R. Rotational co-culture of clonal β-cells with endothelial cells: effect of PPAR-γ agonism in vitro on insulin and VEGF secretion. Diabetes Obes Metab 2011;13(7):662-8.

Pesaro AE, de Matos Soeiro A, Serrano CV, Giraldez RR, Ladeira RT, Nicolau JC. Effect of beta-blockers on the risk of atrial fibrillation in patients with acute myocardial infarction. Clinics (Sao Paulo) 2010;65(3):265-70.

Piven OO, Winata CL. The canonical way to make a heart: β-catenin and plakoglobin in heart development and remodeling. Exp Biol Med (Maywood) 2017;242(18):1735-45.

Posma JJ, Grover SP, Hisada Y, Owens AP, 3rd, Antoniak S, Spronk HM, et al. Roles of coagulation proteases and PARs (Protease-Activated Receptors) in mouse models of inflammatory diseases. Arterioscler Thromb Vasc Biol 2019;39(1):13-24.

Qi X, Sun X, Li X, Kong D, Zhao L. Significance changes in the levels of myocardial enzyme in the child patients with Mycoplasma Pneumoniae Pneumonia. Cell Mol Biol (Noisy-le-grand) 2020;66(6):41-5.

Rong SL, Wang XL, Wang YC, Wu H, Zhou XD, Wang ZK, et al. Anti-inflammatory activities of hepatocyte growth factor in post-ischemic heart failure. Acta Pharmacol Sin 2018;39(10):1613-21.

Sheu JJ, Hsiao HY, Chung SY, Chua S, Chen KH, Sung PH, et al. Endothelial progenitor cells, rosuvastatin and valsartan have a comparable effect on repair of balloon-denudated carotid artery injury. Am J Transl Res 2019;11(3):1282-98.

Somasuntharam I, Yehl K, Carroll SL, Maxwell JT, Martinez MD, Che PL, et al. Knockdown of TNF-α by DNAzyme gold nanoparticles as an anti-inflammatory therapy for myocardial infarction. Biomaterials 2016;83:12-22.

Song LL, Zhang Y, Zhang XR, Song YN, Dai HZ. Theacrine attenuates myocardial fibrosis after myocardial infarction via the SIRT3/β-catenin/PPARγ pathway in estrogen-deficient mice. Eur Rev Med Pharmacol Sci 2019;23(12):5477-86.

Sun C, Li X, Wang D, Wang L. Therapeutic and diagnostic value of Caspase-12 and study of growth differentiation factor-15 in patients with acute myocar-dial infarction. Iran J Public Health 2020;49(12):2339-47.

Sun C, Zhang X, Yu F, Liu C, Hu F, Liu L, et al. Atractylenolide I alleviates ischemia/reperfusion injury by preserving mitochondrial function and inhibiting caspase-3 activity. J Int Med Res 2021;49(2):300060521993315.

Sun L, Jia H, Li J, Yu M, Yang Y, Tian D, et al. Cecal Gut Microbiota and Metabolites Might Contribute to the Severity of Acute Myocardial Ischemia by Impacting the Intestinal Permeability, Oxidative Stress, and Energy Metabolism. Front Microbiol 2019;10:1745.

Sun Z, Pang S, Cui Y, Yan B. Genetic and Functional Variants Analysis of the GATA6 Gene Promoter in Acute Myocardial Infarction. Front Genet 2019;10:1100.

Tai S, Tang JJ, Tang L, Ni YQ, Guo Y, Hu XQ, et al. Management and Outcome of Ventricular Septal Rupture Complicating Acute Myocardial Infarction: What Is New in the Era of Percutaneous Intervention? Cardiology 2018;141(4):226-32.

Veltman D, Wu M, Pokreisz P, Claus P, Gillijns H, Caluwé E, et al. Clec4e-Receptor Signaling in Myocardial Repair After Ischemia-Reperfusion Injury. JACC Basic Transl Sci 2021;6(8):631-46.

Wang DM, Jin JJ, Tian LM, Zhang Z. MiR-195 promotes myocardial fibrosis in MI rats via targeting TGF-β1/Smad. J Biol Regul Homeost Agents 2020;34(4):1325-32.

Wang Y, Qi X, Wang C, Zhao D, Wang H, Zhang J. Effects of propofol on myocardial ischemia-reperfusion injury in rats with type-2 diabetes mellitus. Biomed Rep 2017;6(1):69-74.

Wei L, Sun X, Qi X, Zhang Y, Li Y, Xu Y. Dihydromyricetin ameliorates cardiac ischemia/reperfusion injury through sirt3 activation. Biomed Res Int 2019;2019:6803943.

Wu R, Gao W, Dong Z, Su Y, Ji Y, Liao J, et al. Plasma heat shock protein 70 is associated with the onset of acute myocardial infarction and total occlusion in target vessels. Front Cardiovasc Med 2021;8:688702.

Xu Y, Gu Q, Liu N, Yan Y, Yang X, Hao Y, et al. PPARγ alleviates right ventricular failure secondary to pulmonary arterial hypertension in rats. Int Heart J 2017;58(6):948-56.

Yang H, Liu S, Du H, Hong Z, Lv Y, Nie C, et al. Hydrogen attenuates myocardial injury in rats by regulating oxidative stress and NLRP3 inflammasome mediated pyroptosis. Int J Med Sci 2021;18(14):3318-25.

Yin H, Liu Z, Li F, Ni M, Wang B, Qiao Y, et al. Ginsenoside-Rg1 enhances angiogenesis and ameliorates ventricular remodeling in a rat model of myocardial infarction. J Mol Med (Berl) 2011;89(4):363-75.

Yu R, Yu BX, Chen JF, Lv XY, Yan ZJ, Cheng Y, et al. Anti-tumor effects of Atractylenolide I on bladder cancer cells. J Exp Clin Cancer Res 2016;35:40.

Zaatari G, Fintel DJ, Subacius H, Germano JJ, Shani J, Goldberger JJ. Comparison of metoprolol versus carvedilol after acute myocardial infarction. Am J Cardiol 2021;147:1-7.

Zhao J, Yu H, Yan P, Zhou X, Wang Y, Yao Y. Circulating MicroRNA-499 as a diagnostic biomarker for acute myocardial infarction: A Meta-analysis. Dis Markers 2019;2019:6121696.

Zhao M, Fan C, Ernst PJ, Tang Y, Zhu H, Mattapally S, et al. Y-27632 preconditioning enhances transplantation of human-induced pluripotent stem cell-derived cardiomyocytes in myocardial infarction mice. Cardiovasc Res 2019;115(2):343-56.

Zhao X, Gao S, Kajigaya S, Liu Q, Wu Z, Feng X, et al. Comprehensive analysis of single-cell RNA sequencing data from healthy human marrow hematopoietic cells. BMC Res Notes 2020;13(1):514.

Zhou Y, Wang X, Lan S, Zhang L, Niu G, Zhang G. Application of evidence-based nursing in patients with acute myocardial infarction complicated with heart failure. Am J Transl Res 2021;13(5):5641-6.

Zhou Y, Chen P, Liu Q, Wang Y, Zhang L, Wu R, et al. Hepatoma-derived growth factor secreted from mesenchymal stem cells reduces myocardial Ischemia-reperfusion injury. Stem Cells Int 2017;2017:1096980.

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Published

2023-05-19

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How to Cite

Protective Effect of Combined Metoprolol and Atractylenolide I in Rats with Acute Myocardial Infarction via Modulation of the SIRT3/β-CATENIN/PPAR-γ Signaling Pathway Article. (2023). Brazilian Journal of Pharmaceutical Sciences, 59, e21639. https://doi.org/10.1590/s2175-97902023e21639