{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:11:32Z","timestamp":1790662292421,"version":"4.1.0"},"reference-count":57,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T00:00:00Z","timestamp":1741651200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Rejuvenation Research"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:p>\n                    The aim of this study is to elucidate the pharmacological mechanism underlying the effects of Ginseng Radix et Rhizoma (ginseng) in heart failure (HF), providing a theoretical foundation for its clinical application. The potential mechanism of ginseng in the context of HF was investigated using systems pharmacology that combined network pharmacology, Gene Expression Omnibus (GEO) analysis, molecular docking, and experimental verification. Network pharmacology was employed to identify drug-disease targets. Core gene targets were subsequently subjected to enrichment analysis by integrating network pharmacology with GEO. Molecular docking was utilized to predict the binding affinities between identified targets and ginseng compounds. Furthermore, the therapeutic efficacy of ginseng was validated in an isoproterenol (ISO)-induced rat model of HF. The modulation of key signaling pathways by ginseng was confirmed through Western blot analysis. A total of 154 potential targets of ginseng in the treatment of HF were identified through network pharmacology analysis. The analysis of GSE71613 revealed that the PI3K-Akt pathway, reactive oxygen species, oxidative phosphorylation, MAPK signaling, and Ras signaling pathways are predominantly associated with patients with HF. By integrating the findings from network pharmacology and GEO analysis, ginsenoside Rg1 and ginsenoside Rb3 were identified as the potential components in ginseng, while\n                    <jats:italic toggle=\"yes\">FN1<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">PRKAA2<\/jats:italic>\n                    were recognized as key targets involved in the PI3K-AKT and AMPK pathways, respectively. Molecular docking analysis revealed a strong affinity between the potential components and the identified core targets.\n                    <jats:italic toggle=\"yes\">In vivo<\/jats:italic>\n                    experiments indicated that the extract of ginseng (EPG) significantly ameliorated ISO-induced cardiac dysfunction by improving cardiac parameters such as cardiac left ventricular internal systolic diameter, left ventricular end-diastolic volume, left ventricular end systolic volume, and left ventricular ejection fraction, while also reducing malondialdehyde production. In addition, EPG was found to enhance superoxide dismutase activity and ATP levels, while concurrently reducing the levels of interleukin (IL)-1\u03b2, IL-6, and TNF-\u03b1. The extract also reduced myocardial oxygen consumption, inflammatory cell infiltration, and the number of damaged myocardial fibers. Moreover, EPG was observed to upregulate the expression of p-PI3K, p-AKT, p-AMPK, and Bcl-2, while downregulating the expression of p-NF\u03baB, TGF-\u03b2, and Bax. The therapeutic effects of ginseng on HF are primarily mediated through the PI3K-Akt and AMPK pathways. Ginsenoside Rg1 and ginsenoside Rb3 have been identified as potential therapeutic agents for HF.\n                  <\/jats:p>","DOI":"10.1089\/rej.2024.0051","type":"journal-article","created":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T18:50:50Z","timestamp":1730919050000},"page":"54-66","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":10,"title":["Systems Pharmacology to Explore the Potential Mechanism of Ginseng Against Heart Failure"],"prefix":"10.1177","volume":"28","author":[{"given":"Kai","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi\u2019an, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi\u2019an, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Mu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi\u2019an, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meina","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi\u2019an, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi\u2019an, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingru","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi\u2019an, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi\u2019an, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi\u2019an, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,3,11]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.123.011095"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.69.1.107"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b20-00783"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.106725"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202216928"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2021.111395"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03573-5"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/CRD.0000000000000303"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.112463"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.121.318241"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1097\/HM9.0000000000000085"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgr.2017.10.004"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgr.2020.02.004"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/8427519"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1097\/HM9.0000000000000096"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.603142"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgr.2015.12.009"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgr.2023.04.006"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.3390\/foods12234316"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/os.13971"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgr.2022.08.001"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms242316736"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgr.2016.12.012"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2012.01.002"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2021.105843"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102610"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.31083\/j.rcm2407212"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-021-00830-1"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgr.2021.11.009"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgr.2023.06.007"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1327033"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.109487"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbdv.202200730"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2023.175676"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2024.118506"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfn026"},{"issue":"3","key":"e_1_3_4_38_2","first-page":"281","article-title":"Experimental cardiac hypertrophy induced by isoproterenol in the rat","volume":"46","author":"Szabo J","year":"1975","unstructured":"Szabo J, , Csaky L, , Szegi J. Experimental cardiac hypertrophy induced by isoproterenol in the rat. Acta Physiol Acad Sci Hung, 1975; 46(3):281\u2013285.","journal-title":"Acta Physiol Acad Sci Hung"},{"issue":"1","key":"e_1_3_4_39_2","article-title":"Sundarban honey confers protection against isoproterenol\u2010induced myocardial infarction in Wistar rats","volume":"2016","author":"Afroz R","year":"2016","unstructured":"Afroz R, , Tanvir E, , Karim N, et al. Sundarban honey confers protection against isoproterenol\u2010induced myocardial infarction in Wistar rats. Biomed Res Int, 2016; 2016(1):6437641.","journal-title":"Biomed Res Int"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chmed.2022.02.006"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/5786053"},{"issue":"1","key":"e_1_3_4_42_2","article-title":"Exploring the pharmacological mechanism of duhuo jisheng decoction in treating osteoporosis based on network pharmacology","volume":"2021","author":"Xiong Z","year":"2021","unstructured":"Xiong Z, , Zheng C, , Chang Y, et al. Exploring the pharmacological mechanism of duhuo jisheng decoction in treating osteoporosis based on network pharmacology. Evid Based Complement Alternat Med, 2021; 2021(1):5510290.","journal-title":"Evid Based Complement Alternat Med"},{"issue":"1","key":"e_1_3_4_43_2","article-title":"Network pharmacology\u2010based analysis on the curative effect of kunxian capsules against rheumatoid arthritis","volume":"2021","author":"Yan H-X","year":"2021","unstructured":"Yan H-X, , Xu C-F, , Yang H, et al. Network pharmacology\u2010based analysis on the curative effect of kunxian capsules against rheumatoid arthritis. Evid Based Complement Alternat Med, 2021; 2021(1):6812374.","journal-title":"Evid Based Complement Alternat Med"},{"issue":"1","key":"e_1_3_4_44_2","first-page":"69","article-title":"Identification of microRNA and Analysis of Target Genes in Panax ginseng","volume":"15","author":"Wang Y","year":"2023","unstructured":"Wang Y, , Chen Y, , Peng M, et al. Identification of microRNA and Analysis of Target Genes in Panax ginseng. Chin Herb Med, 2023; 15(1):69\u201375.","journal-title":"Chin Herb Med"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2018.05.006"},{"issue":"1","key":"e_1_3_4_46_2","article-title":"Efficacy and safety of shengmai injection for chronic heart failure: A systematic review of randomized controlled trials","volume":"2020","author":"Wang Y","year":"2020","unstructured":"Wang Y, , Zhou X, , Chen X, et al. Efficacy and safety of shengmai injection for chronic heart failure: A systematic review of randomized controlled trials. Evid Based Complement Alternat Med, 2020; 2020(1):9571627.","journal-title":"Evid Based Complement Alternat Med"},{"key":"e_1_3_4_47_2","article-title":"Calycosin as a novel PI3K activator reduces inflammation and fibrosis in heart failure through AKT\u2013IKK\/STAT3 axis","volume":"13","author":"Wang X","year":"2022","unstructured":"Wang X, , Li W, , Zhang Y, et al. Calycosin as a novel PI3K activator reduces inflammation and fibrosis in heart failure through AKT\u2013IKK\/STAT3 axis. Front Pharmacol, 2022; 13:828061.","journal-title":"Front Pharmacol"},{"key":"e_1_3_4_48_2","article-title":"Linggui Zhugan Decoction activates the SIRT1-AMPK-PGC1\u03b1 signaling pathway to improve mitochondrial and oxidative damage in rats with chronic heart failure caused by myocardial infarction","volume":"14","author":"Yu S","year":"2023","unstructured":"Yu S, , Qian H, , Tian D, et al. Linggui Zhugan Decoction activates the SIRT1-AMPK-PGC1\u03b1 signaling pathway to improve mitochondrial and oxidative damage in rats with chronic heart failure caused by myocardial infarction. Front Pharmacol, 2023; 14:1074837.","journal-title":"Front Pharmacol"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.651150"},{"issue":"1","key":"e_1_3_4_50_2","article-title":"Exploring the therapeutic mechanism of Tingli Dazao Xiefei decoction on heart failure based on network pharmacology and experimental study","volume":"2021","author":"Zhao D-D","year":"2021","unstructured":"Zhao D-D, , Zhang X-Q, , Yang T, et al. Exploring the therapeutic mechanism of Tingli Dazao Xiefei decoction on heart failure based on network pharmacology and experimental study. Evid Based Complement Alternat Med, 2021; 2021(1):6645878.","journal-title":"Evid Based Complement Alternat Med"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S393995"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2017.95"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.09.013"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06161"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13753"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2018.03.004"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000036576"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-61926-2"}],"container-title":["Rejuvenation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/rej.2024.0051","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/rej.2024.0051","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/rej.2024.0051","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T01:36:22Z","timestamp":1777685782000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/rej.2024.0051"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,11]]},"references-count":57,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1089\/rej.2024.0051"],"URL":"https:\/\/doi.org\/10.1089\/rej.2024.0051","relation":{},"ISSN":["1549-1684","1557-8577"],"issn-type":[{"value":"1549-1684","type":"print"},{"value":"1557-8577","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,11]]}}}