{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:51:31Z","timestamp":1791287491296,"version":"4.1.0"},"reference-count":47,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T00:00:00Z","timestamp":1743292800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2023YFC3504000"],"award-info":[{"award-number":["2023YFC3504000"]}]},{"name":"National Key Research and Development Program of China","award":["81703840"],"award-info":[{"award-number":["81703840"]}]},{"name":"National Key Research and Development Program of China","award":["81773860"],"award-info":[{"award-number":["81773860"]}]},{"name":"National Key Research and Development Program of China","award":["81473360"],"award-info":[{"award-number":["81473360"]}]},{"name":"National Natural Science Foundation of China","award":["2023YFC3504000"],"award-info":[{"award-number":["2023YFC3504000"]}]},{"name":"National Natural Science Foundation of China","award":["81703840"],"award-info":[{"award-number":["81703840"]}]},{"name":"National Natural Science Foundation of China","award":["81773860"],"award-info":[{"award-number":["81773860"]}]},{"name":"National Natural Science Foundation of China","award":["81473360"],"award-info":[{"award-number":["81473360"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Heart failure (HF), the terminal stage of cardiovascular disease with high morbidity and mortality, remains poorly managed by current therapies. Ventricular remodeling in HF is fundamentally characterized by myocardial fibrosis. While ginsenoside Rb1 has demonstrated anti-fibrotic effects in HF, the underlying mechanism remains unclear. Twist1, an upstream regulator of energy metabolism factors PGC-1\u03b1 and PPAR\u03b1, may attenuate fibrosis by preserving systemic energy homeostasis, suggesting its pivotal role in HF pathogenesis. This study explores ginsenoside Rb1\u2032s anti-HF mechanisms through the regulation of ginsenoside Rb1 on these metabolic regulators. Methods: Sprague Dawley rats were subjected to a ligation of the left anterior descending coronary artery to induce an HF model, followed by ginsenoside Rb1 treatment for 6 weeks. Therapeutic effects were evaluated through cardiac function assessment, myocardial histopathological staining (HE, Masson, immunofluorescence, immunohistochemistry), mitochondrial morphology observation (transmission electron microscopy), energy metabolism analysis (electron transport chain efficiency, mitochondrial membrane potential, ATP content), and protein expression profiling (Twist1, PGC-1\u03b1, PPAR\u03b1, GLUT4, PPAR\u03b3). Additionally, H9c2 cells induced with endothelin-1 to model HF were employed as an in vitro model to further investigate ginsenoside Rb1\u2032s regulatory effects on the Twist1\/PGC-1\u03b1\/PPAR\u03b1 signaling pathway. Results: Ginsenoside Rb1 can restore cardiac function in HF rats, improve mitochondrial function, alleviate energy metabolism disorders, and inhibit ventricular remodeling. By modulating the Twist1\/PGC-1\u03b1\/PPAR\u03b1 signaling pathway, ginsenoside Rb1 suppressed the abnormal overexpression of Twist1 and maintained normal expression of downstream PGC-1\u03b1 and PPAR\u03b1. In vitro experiments further demonstrated that ginsenoside Rb1 significantly inhibited Twist1 expression in H9c2 cardiomyocytes with HF while promoting PGC-1\u03b1 and PPAR\u03b1 expression, thereby restoring myocardial energy metabolism and mitigating ventricular remodeling in HF. Conclusions: Ginsenoside Rb1 can inhibit the upregulation of Twist1 and activate the expression of its downstream PGC-1\u03b1 and PPAR\u03b1 expression, by modulating the Twist1\/PGC-1\u03b1\/PPAR\u03b1 signaling pathway, alleviating ventricular remodeling in HF patients and improving myocardial energy metabolism dysfunction. Twist1 may be a key target for the treatment of HF. This study not only elucidates the mechanism by which ginsenoside Rb1 alleviates HF, but also provides new insights into the clinical treatment of HF.<\/jats:p>","DOI":"10.3390\/ph18040500","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T05:21:04Z","timestamp":1743398464000},"page":"500","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Ginsenoside Rb1 Ameliorates Heart Failure Ventricular Remodeling by Regulating the Twist1\/PGC-1\u03b1\/PPAR\u03b1 Signaling Pathway"],"prefix":"10.3390","volume":"18","author":[{"given":"Ziwei","family":"Zhou","sequence":"first","affiliation":[{"name":"School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhimin","family":"Song","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomeng","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meijing","family":"Li","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China"},{"name":"Beijing Key Laboratory of Traditional Chinese Medicine Collateral Disease Theory Research, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muxin","family":"Gong","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China"},{"name":"Beijing Key Laboratory of Traditional Chinese Medicine Collateral Disease Theory Research, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3272","DOI":"10.1093\/cvr\/cvac013","article-title":"Global burden of heart failure: A comprehensive and updated review of epidemiology","volume":"118","author":"Savarese","year":"2023","journal-title":"Cardiovasc. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1007\/s10741-024-10423-9","article-title":"Stress echocardiography in heart failure patients: Additive value and caveats","volume":"29","author":"Pastore","year":"2024","journal-title":"Heart Fail. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"106035","DOI":"10.1016\/j.phrs.2021.106035","article-title":"Current and future therapeutic perspective in chronic heart failure","volume":"175","author":"Mascolo","year":"2022","journal-title":"Pharmacol. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"104224","DOI":"10.1016\/j.lpm.2024.104224","article-title":"Heart failure: A major public health problem","volume":"53","author":"Daubert","year":"2024","journal-title":"Presse Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s40261-023-01253-y","article-title":"Vericiguat for the Treatment of Heart Failure with Reduced Ejection Fraction Following a Worsening Heart Failure Event: A Cost-Effectiveness Analysis from the Perspective of Chinese Healthcare Providers","volume":"43","author":"Yu","year":"2023","journal-title":"Clin. Drug Investig."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3716","DOI":"10.1172\/JCI120849","article-title":"Mitochondrial dysfunction in pathophysiology of heart failure","volume":"128","author":"Zhou","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"100822","DOI":"10.1016\/j.mam.2019.09.006","article-title":"Emerging role of mitophagy in cardiovascular physiology and pathology","volume":"71","author":"Morales","year":"2020","journal-title":"Mol. Aspects Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.yjmcc.2013.01.016","article-title":"Mitochondria-mediated cardioprotection by trimetazidine in rabbit heart failure","volume":"59","author":"Dedkova","year":"2013","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1111\/j.1472-8206.2009.00802.x","article-title":"Effects of trimetazidine, a partial inhibitor of fatty acid oxidation, on ventricular function and survival after myocardial infarction and reperfusion in the rat","volume":"24","author":"Mouquet","year":"2010","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.jgr.2022.07.002","article-title":"Ginseng polysaccharides: Potential antitumor agents","volume":"47","author":"Tao","year":"2023","journal-title":"J. Ginseng Res."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Du, L., Lu, H., Wang, Z., Liu, C., Xiao, Y., Guo, Z., and Li, Y. (2023). Therapeutic Potential of Ginsenoside Rb1-PLGA Nanoparticles for Heart Failure Treatment via the ROS\/PPAR\u03b1\/PGC1\u03b1 Pathway. Molecules, 28.","DOI":"10.3390\/molecules28248118"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.jconrel.2024.06.015","article-title":"Enhancing myocardial infarction treatment through bionic hydrogel-mediated spatial combination therapy via mtDNA-STING crosstalk modulation","volume":"371","author":"Zheng","year":"2024","journal-title":"J. Control. Release"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"155880","DOI":"10.1016\/j.phymed.2024.155880","article-title":"Ginsenoside Rb1 ameliorates heart failure through DUSP-1-TMBIM-6-mediated mitochondrial quality control and gut flora interactions","volume":"132","author":"Pu","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1142\/S0192415X20500676","article-title":"Ginsenoside Rb1 Ameliorates Age-Related Myocardial Dysfunction by Regulating the NF-\u03baB Signaling Pathway","volume":"48","author":"Ke","year":"2020","journal-title":"Am. J. Chin. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"175676","DOI":"10.1016\/j.ejphar.2023.175676","article-title":"Ginsenoside Rb1 promotes the activation of PPAR\u03b1 pathway via inhibiting FADD to ameliorate heart failure","volume":"947","author":"Li","year":"2023","journal-title":"Eur. J. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.ydbio.2008.02.037","article-title":"Twist1 function in endocardial cushion cell proliferation, migration, and differentiation during heart valve development","volume":"317","author":"Shelton","year":"2008","journal-title":"Dev. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"18013","DOI":"10.1021\/acs.jafc.4c03677","article-title":"Fucoxanthin Mitigates High-Fat-Induced Lipid Deposition and Insulin Resistance in Skeletal Muscle through Inhibiting PKM1 Activity","volume":"72","author":"Wu","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Mohan, U.P., Pichiah, P.B.T., and Arunachalam, S. (2023). Adriamycin downregulates the expression of KLF4 in cardiomyocytes in vitro and contributes to impaired cardiac energy metabolism in Adriamycin-induced cardiomyopathy. 3 Biotech., 13.","DOI":"10.1007\/s13205-023-03584-1"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3758","DOI":"10.7150\/thno.71722","article-title":"Twist1 downregulation of PGC-1\u03b1 decreases fatty acid oxidation in tubular epithelial cells, leading to kidney fibrosis","volume":"12","author":"Liu","year":"2022","journal-title":"Theranostics"},{"key":"ref_20","first-page":"e876","article-title":"2022 AHA\/ACC\/HFSA Guideline for the Management of Heart Failure: Executive Summary: A Report of the American College of Cardiology\/American Heart Association Joint Committee on Clinical Practice Guidelines","volume":"145","author":"Heidenreich","year":"2022","journal-title":"Circulation"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e15064","DOI":"10.1111\/dme.15064","article-title":"Diagnostic and prognostic biomarkers reflective of cardiac remodelling in diabetes mellitus: A scoping review","volume":"40","author":"Chhor","year":"2023","journal-title":"Diabet. Med."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Dong, T., Zhu, W., Yang, Z., Matos Pires, N.M., Lin, Q., Jing, W., Zhao, L., Wei, X., and Jiang, Z. (2024). Advances in heart failure monitoring: Biosensors targeting molecular markers in peripheral bio-fluids. Biosens. Bioelectron., 255.","DOI":"10.1016\/j.bios.2024.116090"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1002\/humu.24470","article-title":"Mutation update for the ACTN2 gene","volume":"43","author":"Olive","year":"2022","journal-title":"Hum. Mutat."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1039\/C6MB00813E","article-title":"Identification of active components in Yixinshu Capsule with protective effects against myocardial dysfunction on human induced pluripotent stem cell-derived cardiomyocytes by an integrative approach","volume":"13","author":"Zhang","year":"2017","journal-title":"Mol. Biosyst."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1038\/s12276-022-00800-5","article-title":"Cardiac-specific overexpression of Ndufs1 ameliorates cardiac dysfunction after myocardial infarction by alleviating mitochondrial dysfunction and apoptosis","volume":"54","author":"Qi","year":"2022","journal-title":"Exp. Mol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Yang, Z.-Q., Han, Y.-Y., Gao, F., Tian, J.-Y., Bai, R., Guo, Q.-H., and Liu, X.-C. (2023). Shengxian decoction protects against chronic heart failure in a rat model via energy regulation mechanisms. BMC Complement. Med. Ther., 23.","DOI":"10.1186\/s12906-023-04035-3"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.1042\/CS20171167","article-title":"Mechanisms contributing to cardiac remodelling","volume":"131","author":"Wu","year":"2017","journal-title":"Clin. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1161\/CIRCRESAHA.121.318241","article-title":"Cardiac Energy Metabolism in Heart Failure","volume":"128","author":"Lopaschuk","year":"2021","journal-title":"Circ. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"105263","DOI":"10.1016\/j.phrs.2020.105263","article-title":"Chemical constituents of Panax ginseng and Panax notoginseng explain why they differ in therapeutic efficacy","volume":"161","author":"Liu","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"118723","DOI":"10.1016\/j.jep.2024.118723","article-title":"A novel glycopeptide from mountain-cultivated ginseng residue protects type 2 diabetic symptoms-induced heart failure","volume":"336","author":"Li","year":"2025","journal-title":"J. Ethnopharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"118506","DOI":"10.1016\/j.jep.2024.118506","article-title":"Overview of Panax ginseng and its active ingredients protective mechanism on cardiovascular diseases","volume":"334","author":"Zhou","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"176609","DOI":"10.1016\/j.ejphar.2024.176609","article-title":"Ginsenoside Rb1 ameliorates lipotoxicity-induced myocardial injury in diabetes mellitus by regulating Mfn2","volume":"974","author":"Ji","year":"2024","journal-title":"Eur. J. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1038\/aps.2010.52","article-title":"Ginsenoside Rb1 protects cardiomyocytes against CoCl2-induced apoptosis in neonatal rats by inhibiting mitochondria permeability transition pore opening","volume":"31","author":"Kong","year":"2010","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5623","DOI":"10.7150\/thno.44836","article-title":"Branched chain amino acids exacerbate myocardial ischemia\/reperfusion vulnerability via enhancing GCN2\/ATF6\/PPAR-\u03b1 pathway-dependent fatty acid oxidation","volume":"10","author":"Li","year":"2020","journal-title":"Theranostics"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.cmet.2005.05.004","article-title":"Metabolic control through the PGC-1 family of transcription coactivators","volume":"1","author":"Lin","year":"2005","journal-title":"Cell Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1186\/s12964-023-01262-6","article-title":"Roles of Twist1 in lipid and glucose metabolism","volume":"21","author":"Huang","year":"2023","journal-title":"Cell Commun. Signal"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.cell.2009.01.051","article-title":"Twist-1 is a PPARdelta-inducible, negative-feedback regulator of PGC-1alpha in brown fat metabolism","volume":"137","author":"Pan","year":"2009","journal-title":"Cell"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Vonh\u00f6gen, I.G.C., El Azzouzi, H., Olieslagers, S., Vasilevich, A., de Boer, J., Tinahones, F.J., da Costa Martins, P.A., de Windt, L.J., and Murri, M. (2020). MiR-337-3p Promotes Adipocyte Browning by Inhibiting TWIST1. Cells, 9.","DOI":"10.3390\/cells9041056"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/s41419-018-1282-6","article-title":"Thymidine phosphorylase promotes malignant progression in hepatocellular carcinoma through pentose Warburg effect","volume":"10","author":"Zhang","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_40","first-page":"2303","article-title":"Effect and mechanism of miR-223 on fibrosis-related signaling pathway in rat cardiomyocytes","volume":"100","author":"Zhang","year":"2020","journal-title":"Chin. Med. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1161\/CIRCRESAHA.116.308870","article-title":"TWIST1 Integrates Endothelial Responses to Flow in Vascular Dysfunction and Atherosclerosis","volume":"119","author":"Mahmoud","year":"2016","journal-title":"Circ. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1111\/jcmm.13465","article-title":"Emerging role of Twist1 in fibrotic diseases","volume":"22","author":"Ning","year":"2018","journal-title":"J. Cell Mol. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.ydbio.2010.08.021","article-title":"Twist1 promotes heart valve cell proliferation and extracellular matrix gene expression during development in vivo and is expressed in human diseased aortic valves","volume":"347","author":"Chakraborty","year":"2010","journal-title":"Dev. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1002\/cbin.11944","article-title":"The paired-related homeobox protein 1 promotes cardiac fibrosis via the Twist1-Prrx1-tenascin-C loop","volume":"47","author":"Wang","year":"2023","journal-title":"Cell Biol. Int."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1096\/fj.201800673RR","article-title":"Signature-oriented investigation of the efficacy of multicomponent drugs against heart failure","volume":"33","author":"Wei","year":"2019","journal-title":"FASEB J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"154185","DOI":"10.1016\/j.phymed.2022.154185","article-title":"Yi-Xin-Shu capsule ameliorates cardiac hypertrophy by regulating RB\/HDAC1\/GATA4 signaling pathway based on proteomic and mass spectrometry image analysis","volume":"103","author":"Zhang","year":"2022","journal-title":"Phytomedicine"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1016\/j.cell.2023.12.032","article-title":"DNA-guided transcription factor cooperativity shapes face and limb mesenchyme","volume":"187","author":"Kim","year":"2024","journal-title":"Cell"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/4\/500\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:05:57Z","timestamp":1760029557000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/4\/500"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,30]]},"references-count":47,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["ph18040500"],"URL":"https:\/\/doi.org\/10.3390\/ph18040500","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,30]]}}}