Calycosin-7-O-β-d-glucoside attenuates myocardial ischemia–reperfusion injury by activating JAK2/STAT3 signaling pathway via the regulation of IL-10 secretion in mice
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Calycosin-7-O-β-d-glucoside (CG) is the component of Astragali Radix, and the aim of the present study is to investigate whether CG protects myocardium from I/R-induced damage by the regulation of IL-10/JAK2/STAT3 signaling pathway. H9C2 cells were subjected to I/R treatment and pretreated with 1 μm CG in vitro. In addition, a mouse model of myocardial I/R injury was induced by left anterior descending (LAD) coronary artery ligation and administrated with 30 mg/kg CG by intravenous injection before I/R surgery. In vitro and in vivo results showed that CG up-regulated IL-10 level, activated the JAK2/STAT3 pathway, and protected myocardial cells from I/R-induced apoptosis. The hemodynamic measurement, TTC staining, TUNEL staining, and western blot results in vivo showed that the protective effects of CG on myocardial function and cell apoptosis were all reversed by the IL-10R α neutralizing antibody. CG-induced phosphorylation activation of JAK2/STAT3 signaling pathway was also suppressed by the blocking of IL-10. In summary, these findings suggest that CG might alleviate myocardial I/R injury by activating the JAK2/STAT3 signaling pathway via up-regulation of IL-10 secretion, which provides us insights into the mechanism underlying the protective effect of CG on myocardial I/R injury.
KeywordsCalycosin-7-O-β-d-glucoside Myocardial ischemia–reperfusion IL-10 JAK2/STAT3 signaling pathway
This study was supported by grants from the National Natural Science Foundation of China (Nos. 81701720 and 81571680).
Compliance with ethical standards
Conflict of interest
All authors declare that there are no conflicts of interest in this study.
This article does not contain any studies with human participants performed by any of the authors. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.
- 1.Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Magid D, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER, Moy CS, Mussolino ME, Nichol G, Paynter NP, Schreiner PJ, Sorlie PD, Stein J, Turan TN, Virani SS, Wong ND, Woo D, Turner MB (2013) Executive summary: heart disease and stroke statistics—2013 update: a report from the American Heart Association. Circulation 127(1):143–152. https://doi.org/10.1161/CIR.0b013e318282ab8f CrossRefPubMedGoogle Scholar
- 2.Cannon CP, Gibson CM, Lambrew CT, Shoultz DA, Levy D, French WJ, Gore JM, Weaver WD, Rogers WJ, Tiefenbrunn AJ (2000) Relationship of symptom-onset-to-balloon time and door-to-balloon time with mortality in patients undergoing angioplasty for acute myocardial infarction. JAMA 283(22):2941–2947CrossRefGoogle Scholar
- 5.Cao J, Xie H, Sun Y, Zhu J, Ying M, Qiao S, Shao Q, Wu H, Wang C (2015) Sevoflurane post-conditioning reduces rat myocardial ischemia reperfusion injury through an increase in NOS and a decrease in phopshorylated NHE1 levels. Am J Transl Res 36(6):1529–1537. https://doi.org/10.3892/ijmm.2015.2366 CrossRefGoogle Scholar
- 6.Liu XH, Zhao JB, Guo L, Yang YL, Hu F, Zhu RJ, Feng SL (2014) Simultaneous determination of calycosin-7-O-beta-d-glucoside, ononin, calycosin, formononetin, astragaloside IV, and astragaloside II in rat plasma after oral administration of Radix Astragali extraction for their pharmacokinetic studies by ultra-pressure liquid chromatography with tandem mass spectrometry. Am J Transl Res 70(1):677–686. https://doi.org/10.1007/s12013-014-9972-x CrossRefGoogle Scholar
- 10.Fu S, Gu Y, Jiang JQ, Chen X, Xu M, Shen J (2014) Calycosin-7-O-beta-d-glucoside regulates nitric oxide/caveolin-1/matrix metalloproteinases pathway and protects blood-brain barrier integrity in experimental cerebral ischemia–reperfusion injury. J Ethnopharmacol 155(1):692–701. https://doi.org/10.1016/j.jep.2014.06.015 CrossRefPubMedGoogle Scholar
- 11.Manukyan MC, Alvernaz CH, Poynter JA, Wang Y, Brewster BD, Weil BR, Abarbanell AM, Herrmann JL, Crowe BJ, Keck AC, Meldrum DR (2011) Interleukin-10 protects the ischemic heart from reperfusion injury via the STAT3 pathway. Surgery 150(2):231–239. https://doi.org/10.1016/j.surg.2011.05.017 CrossRefPubMedGoogle Scholar
- 12.Gupta M, Han JJ, Stenson M, Maurer M, Wellik L, Hu G, Ziesmer S, Dogan A, Witzig TE (2012) Elevated serum IL-10 levels in diffuse large B-cell lymphoma: a mechanism of aberrant JAK2 activation. Blood 119(12):2844–2853. https://doi.org/10.1182/blood-2011-10-388538 CrossRefPubMedPubMedCentralGoogle Scholar
- 15.Zhou J, Wulfkuhle J, Zhang H, Gu P, Yang Y, Deng J, Margolick JB, Liotta LA, Petricoin E 3rd, Zhang Y (2007) Activation of the PTEN/mTOR/STAT3 pathway in breast cancer stem-like cells is required for viability and maintenance. Proc Natl Acad Sci USA 104(41):16158–16163. https://doi.org/10.1073/pnas.0702596104 CrossRefGoogle Scholar
- 16.Gonzalez-Reyes A, Menaouar A, Yip D, Danalache B, Plante E, Noiseux N, Gutkowska J, Jankowski M (2015) Molecular mechanisms underlying oxytocin-induced cardiomyocyte protection from simulated ischemia–reperfusion. Mol Cell Endocrinol 412:170–181. https://doi.org/10.1016/j.mce.2015.04.028 CrossRefPubMedGoogle Scholar
- 19.Cai ZP, Parajuli N, Zheng X, Becker L (2012) Remote ischemic preconditioning confers late protection against myocardial ischemia–reperfusion injury in mice by upregulating interleukin-10. Basic Res Cardiol 107(4):277. https://doi.org/10.1007/s00395-012-0277-1 CrossRefPubMedPubMedCentralGoogle Scholar
- 27.Krishnamurthy P, Rajasingh J, Lambers E, Qin G, Losordo DW, Kishore R (2009) IL-10 inhibits inflammation and attenuates left ventricular remodeling after myocardial infarction via activation of STAT3 and suppression of HuR. Circ Res 104(2):e9–18. https://doi.org/10.1161/CIRCRESAHA.108.188243 CrossRefPubMedGoogle Scholar
- 28.Markowski P, Boehm O, Goelz L, Haesner AL, Ehrentraut H, Bauerfeld K, Tran N, Zacharowski K, Weisheit C, Langhoff P, Schwederski M, Hilbert T, Klaschik S, Hoeft A, Baumgarten G, Meyer R, Knuefermann P (2013) Pre-conditioning with synthetic CpG-oligonucleotides attenuates myocardial ischemia/reperfusion injury via IL-10 up-regulation. Basic Res Cardiol 108(5):376. https://doi.org/10.1007/s00395-013-0376-7 CrossRefPubMedPubMedCentralGoogle Scholar
- 30.Yang Y, Duan W, Jin Z, Yi W, Yan J, Zhang S, Wang N, Liang Z, Li Y, Chen W, Yi D, Yu S (2013) JAK2/STAT3 activation by melatonin attenuates the mitochondrial oxidative damage induced by myocardial ischemia/reperfusion injury. J Pineal Res 55(3):275–286. https://doi.org/10.1111/jpi.12070 CrossRefPubMedGoogle Scholar
- 34.Duan W, Yang Y, Yan J, Yu S, Liu J, Zhou J, Zhang J, Jin Z, Yi D (2012) The effects of curcumin post-treatment against myocardial ischemia and reperfusion by activation of the JAK2/STAT3 signaling pathway. Basic Res Cardiol 107(3):263. https://doi.org/10.1007/s00395-012-0263-7 CrossRefPubMedGoogle Scholar
- 37.Fan Y, Zhang R, Liu B, Zhang Z (2001) Studies on association between lipoprotein lipase gene polymorphisms of Pvu II site and hypertriglyceridemics in Chinese. Chin J Med Genet 18(4):296–298Google Scholar
- 41.Curato C, Slavic S, Dong J, Skorska A, Altarche-Xifro W, Miteva K, Kaschina E, Thiel A, Imboden H, Wang J, Steckelings U, Steinhoff G, Unger T, Li J (2010) Identification of noncytotoxic and IL-10-producing CD8+AT2R+ T cell population in response to ischemic heart injury. J Immunol 185(10):6286–6293. https://doi.org/10.4049/jimmunol.0903681 CrossRefPubMedGoogle Scholar
- 42.Zhang Y, Wei L, Sun D, Cao F, Gao H, Zhao L, Du J, Li Y, Wang H (2010) Tanshinone IIA pretreatment protects myocardium against ischaemia/reperfusion injury through the phosphatidylinositol 3-kinase/Akt-dependent pathway in diabetic rats. Diabetes Obes Metab 12(4):316–322. https://doi.org/10.1111/j.1463-1326.2009.01166.x CrossRefPubMedGoogle Scholar