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Hydroethanolic extract of Cirsium setidens ameliorates doxorubicin-induced cardiotoxicity by AMPK-PGC-1α-SOD-mediated mitochondrial protection

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dc.contributor.author박상욱-
dc.contributor.author전새봄-
dc.contributor.author이승현-
dc.date.accessioned2024-06-14T03:12:54Z-
dc.date.available2024-06-14T03:12:54Z-
dc.date.issued2024-07-
dc.identifier.issn0944-7113-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/199805-
dc.description.abstractBackground: Doxorubicin (DOX) is an effective anticancer agent. However, the clinical outcomes of DOX-based therapies are severely hampered by their significant cardiotoxicity. Purpose: We investigated the beneficial effects of an ethanol extract of Cirsium setidens (CSE) on DOX-induced cardiomyotoxicity (DICT). Methods: UPLC-TQ/MS analysis was used to identify CSE metabolite profiles. H9c2 rat cardiomyocytes and MDA-MB-231 human breast cancer cells were used to evaluate the effects of CSE on DICT-induced cell death. To elucidate the mechanism underlying it, AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma co-activator l-alpha (PGC1-α), nuclear respiratory factor 1 (NRF1), NRF2, superoxide dismutase (SOD1), and SOD2 expression was detected using western blot analysis. The oxygen consumption rate (OCR), cellular ROS, and mitochondrial membrane potential were measured. Finally, we confirmed the cardioprotective effect of CSE against DICT in both C57BL/6 mice and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC–CMs) by observing various parameters, such as electrophysiological changes, cardiac fibrosis, and cardiac cell death. Results: Chlorogenic acid and nicotiflorin were the major compounds in CSE. Our data demonstrated that CSE blocked DOX-induced cell death of H9c2 cells without hindrance of its apoptotic effects on MDA-MB-231 cells. DOX-induced defects of OCR and mitochondrial membrane potential were recovered in a CSE through upregulation of the AMPK-PGC1-α-NRF1 signaling pathway. CSE accelerated NRF1 translocation to the nucleus, increased SOD activity, and consequently blocked apoptosis in H9c2 cells. In mice treated with 400 mg/kg CSE for 4 weeks, electrocardiogram data, creatine kinase and lactate dehydrogenase levels in the serum, and cardiac fibrosis, were improved. Moreover, various electrophysiological features indicative of cardiac function were significantly enhanced following the CSE treatment of hiPSC–CMs. Conclusion: Our findings demonstrate CSE that ameliorates DICT by protecting mitochondrial dysfunction via the AMP- PGC1α-NRF1 axis, underscoring the therapeutic potential of CSE and its underlying molecular pathways, setting the stage for future investigations into its clinical applications. © 2024-
dc.description.statementOfResponsibilityopen-
dc.formatapplication/pdf-
dc.languageEnglish-
dc.publisherUrban & Fischer Verlag-
dc.relation.isPartOfPHYTOMEDICINE-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.subject.MESHAMP-Activated Protein Kinases* / metabolism-
dc.subject.MESHAnimals-
dc.subject.MESHApoptosis / drug effects-
dc.subject.MESHCardiotoxicity* / drug therapy-
dc.subject.MESHCell Line, Tumor-
dc.subject.MESHCirsium* / chemistry-
dc.subject.MESHDoxorubicin*-
dc.subject.MESHHumans-
dc.subject.MESHMale-
dc.subject.MESHMembrane Potential, Mitochondrial / drug effects-
dc.subject.MESHMice-
dc.subject.MESHMice, Inbred C57BL*-
dc.subject.MESHMyocytes, Cardiac* / drug effects-
dc.subject.MESHPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha* / metabolism-
dc.subject.MESHPlant Extracts* / pharmacology-
dc.subject.MESHRats-
dc.subject.MESHReactive Oxygen Species / metabolism-
dc.subject.MESHSuperoxide Dismutase* / metabolism-
dc.titleHydroethanolic extract of Cirsium setidens ameliorates doxorubicin-induced cardiotoxicity by AMPK-PGC-1α-SOD-mediated mitochondrial protection-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Biochemistry and Molecular Biology (생화학-분자생물학교실)-
dc.contributor.googleauthorJi-Hye Song-
dc.contributor.googleauthorMin-Sun Kim-
dc.contributor.googleauthorSeung-Hyun Lee-
dc.contributor.googleauthorJin-Taek Hwang-
dc.contributor.googleauthorSoo-Hyun Park-
dc.contributor.googleauthorSahng Wook Park-
dc.contributor.googleauthorSae-Bom Jeon-
dc.contributor.googleauthorRu-Ri Lee-
dc.contributor.googleauthorJangho Lee-
dc.contributor.googleauthorHyo-Kyoung Choi-
dc.identifier.doi10.1016/j.phymed.2024.155633-
dc.contributor.localIdA01487-
dc.contributor.localIdA06268-
dc.relation.journalcodeJ02530-
dc.identifier.eissn1618-095X-
dc.identifier.pmid38640859-
dc.subject.keywordCardiac functions-
dc.subject.keywordCirsium setidens-
dc.subject.keywordDoxorubicin-induced cardiotoxicity-
dc.subject.keywordHuman induced pluripotent stem cell-
dc.subject.keywordOxidative stress-
dc.contributor.alternativeNamePark, Sahng Wook-
dc.contributor.affiliatedAuthor박상욱-
dc.contributor.affiliatedAuthor전새봄-
dc.citation.volume129-
dc.citation.startPage155633-
dc.identifier.bibliographicCitationPHYTOMEDICINE, Vol.129 : 155633, 2024-07-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers

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