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Impaired chronotropic and vasodilator reserves limit exercise capacity in patients with heart failure and a preserved ejection fraction. <i>Circulation<\/i>, <b>114<\/b>, 2138\u20132147 (2006).","DOI":"10.1161\/CIRCULATIONAHA.106.632745"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3) Roh J, Hill JA, Singh A, Valero-Munoz M, Sam F. Heart failure with preserved ejection fraction: heterogeneous syndrome, diverse preclinical models. <i>Circ. Res.<\/i>, <b>130<\/b>, 1906\u20131925 (2022).","DOI":"10.1161\/CIRCRESAHA.122.320257"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4) Ponikowski P, Voors AA, Anker SD, <i>et al.<\/i> 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. <i>Eur. J. Heart Fail.<\/i>, <b>18<\/b>, 891\u2013975 (2016).","DOI":"10.1002\/ejhf.592"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5) Yagi A, Fujimoto K, Tanonaka K, Hirai K, Takeo S. Possible active components of tan-shen (<i>Salvia miltiorrhiza<\/i>) for protection of the myocardium against ischemia-induced derangements. <i>Planta Med.<\/i>, <b>55<\/b>, 51\u201354 (1989).","DOI":"10.1055\/s-2006-961824"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6) Li Z, Zou J, Cao D, Ma X. Pharmacological basis of tanshinone and new insights into tanshinone as a multitarget natural product for multifaceted diseases. <i>Biomed. Pharmacother.<\/i>, <b>130<\/b>, 110599 (2020).","DOI":"10.1016\/j.biopha.2020.110599"},{"key":"7","unstructured":"7) Kawahara Y, Tanonaka K, Arino T, Maki T, Ishihara N, Takagi N, Yagi A, Takeo S. Effects of tanshinone VI on insulin-like growth factor-1-induced hypertrophy of isolated cardiomyocytes from neonatal rats. <i>Exp. Clin. Cardiol.<\/i>, <b>9<\/b>, 165\u2013168 (2004)."},{"key":"8","doi-asserted-by":"crossref","unstructured":"8) Maki T, Kawahara Y, Tanonaka K, Yagi A, Takeo S. Effects of tanshinone VI on the hypertrophy of cardiac myocytes and fibrosis of cardiac fibroblasts of neonatal rats. <i>Planta Med.<\/i>, <b>68<\/b>, 1103\u20131107 (2002).","DOI":"10.1055\/s-2002-36337"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9) Arino T, Tanonaka K, Kawahara Y, Maki T, Takagi N, Yagi A, Takeo S. Effects of tanshinone VI on phosphorylation of ERK and Akt in isolated cardiomyocytes and cardiac fibroblasts. <i>Eur. J. Pharmacol.<\/i>, <b>580<\/b>, 298\u2013305 (2008).","DOI":"10.1016\/j.ejphar.2007.11.017"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10) Marunouchi T, Matsumura K, Fuji E, Iwamoto A, Tanonaka K. Simvastatin attenuates cardiac fibrosis under pathophysiological conditions of heart failure with preserved left ventricular ejection fraction by inhibiting TGF-\u03b2 signaling. <i>Pharmacology<\/i>, <b>109<\/b>, 43\u201351 (2024).","DOI":"10.1159\/000534933"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11) Marunouchi T, Kyono M, Kikuchi N, Tanonaka K. Gemfibrozil mitigates caspase-11-driven myocardial pyroptosis in ischemia\/reperfusion injury in mice. <i>J. Mol. Cell. Cardiol. Plus<\/i>, <b>12<\/b>, 100292 (2025).","DOI":"10.1016\/j.jmccpl.2025.100292"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12) Marunouchi T, Nishiumi C, Iinuma S, Yano E, Tanonaka K. Effects of Hsp90 inhibitor on the RIP1-RIP3-MLKL pathway during the development of heart failure in mice. <i>Eur. J. Pharmacol.<\/i>, <b>898<\/b>, 173987 (2021).","DOI":"10.1016\/j.ejphar.2021.173987"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13) Marunouchi T, Onda S, Kurasawa M, Tanonaka K. Angiotensin II is involved in MLKL activation during the development of heart failure following myocardial infarction in rats. <i>Biol. Pharm. Bull.<\/i>, <b>47<\/b>, 809\u2013817 (2024).","DOI":"10.1248\/bpb.b23-00741"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14) Marunouchi T, Ito T, Onda S, Kyo L, Takahashi K, Uchida M, Yano E, Tanonaka K. Effects of 17-AAG on the RIP1\/RIP3\/MLKL pathway during the development of heart failure following myocardial infarction in rats. <i>J. Pharmacol. Sci.<\/i>, <b>147<\/b>, 192\u2013199 (2021).","DOI":"10.1016\/j.jphs.2021.06.009"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15) Marunouchi T, Fujita K, Takahashi K, Namiki S, Kyo L, Uchida M, Yano E, Tanonaka K. Simvastatin attenuates the c-Raf\/Erk and calcineurin-NFATc2 pathways <i>via<\/i> inhibition of Hsp90 activity during the development of heart failure. <i>J. Pharmacol. Sci.<\/i>, <b>151<\/b>, 17\u201327 (2023).","DOI":"10.1016\/j.jphs.2022.11.002"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16) Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. <i>J. Comput. Chem.<\/i>, <b>31<\/b>, 455\u2013461 (2010).","DOI":"10.1002\/jcc.21334"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17) Eberhardt J, Santos-Martins D, Tillack AF, Forli S. AutoDock Vina 1.2.0: new docking methods, expanded force field, and python bindings. <i>J. Chem. Inf. Model.<\/i>, <b>61<\/b>, 3891\u20133898 (2021).","DOI":"10.1021\/acs.jcim.1c00203"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18) Schiattarella GG, Altamirano F, Tong D, French KM, Villalobos E, Kim SY, Luo X, Jiang N, May HI, Wang ZV, Hill TM, Mammen PPA, Huang J, Lee DI, Hahn VS, Sharma K, Kass DA, Lavandero S, Gillette TG, Hill JA. Nitrosative stress drives heart failure with preserved ejection fraction. <i>Nature<\/i>, <b>568<\/b>, 351\u2013356 (2019).","DOI":"10.1038\/s41586-019-1100-z"},{"key":"19","doi-asserted-by":"crossref","unstructured":"19) Yan SH, Zhao NW, Geng ZR, Shen JY, Liu FM, Yan D, Zhou J, Nie C, Huang CC, Fang ZY. Modulations of Keap1-Nrf2 signaling axis by TIIA ameliorated the oxidative stress-induced myocardial apoptosis. <i>Free Radic. Biol. Med.<\/i>, <b>115<\/b>, 191\u2013201 (2018).","DOI":"10.1016\/j.freeradbiomed.2017.12.001"},{"key":"20","doi-asserted-by":"crossref","unstructured":"20) Yang X, Zheng X, Xiao X, Li L. Effects and mechanisms of Salvia miltiorrhiza Bunge extract on myocardial cell apoptosis in rat heart failure model. <i>Acta Cir. Bras.<\/i>, <b>39<\/b>, e396524 (2024).","DOI":"10.1590\/acb396524"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21) Zhang X, Wang Q, Wang X, Chen X, Shao M, Zhang Q, Guo D, Wu Y, Li C, Wang W, Wang Y. Tanshinone IIA protects against heart failure post-myocardial infarction <i>via<\/i> AMPKs\/mTOR-dependent autophagy pathway. <i>Biomed. Pharmacother.<\/i>, <b>112<\/b>, 108599 (2019).","DOI":"10.1016\/j.biopha.2019.108599"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22) Wu S, Lu D, Gajendran B, Hu Q, Zhang J, Wang S, Han M, Xu Y, Shen X. Tanshinone IIA ameliorates experimental diabetic cardiomyopathy by inhibiting endoplasmic reticulum stress in cardiomyocytes <i>via<\/i> SIRT1. <i>Phytother. Res.<\/i>, <b>37<\/b>, 3543\u20133558 (2023).","DOI":"10.1002\/ptr.7831"},{"key":"23","doi-asserted-by":"crossref","unstructured":"23) Yagi A, Takeo S. Anti-inflammatory constituents, aloesin and aloemannan in Aloe species and effects of tanshinon VI in <i>Salvia miltiorrhiza<\/i> on heart. <i>Yakugaku Zasshi<\/i>, <b>123<\/b>, 517\u2013532 (2003).","DOI":"10.1248\/yakushi.123.517"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24) Zhang Z, Yang Z, Wang S, Wang X, Mao J. Targeting MAPK-ERK\/JNK pathway: a potential intervention mechanism of myocardial fibrosis in heart failure. <i>Biomed. Pharmacother.<\/i>, <b>173<\/b>, 116413 (2024).","DOI":"10.1016\/j.biopha.2024.116413"},{"key":"25","doi-asserted-by":"crossref","unstructured":"25) Bueno OF, Molkentin JD. Involvement of extracellular signal-regulated kinases 1\/2 in cardiac hypertrophy and cell death. <i>Circ. 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