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Water Extract of Capsella bursa-pastoris Mitigates Doxorubicin-Induced Cardiotoxicity by Upregulating Antioxidant Enzymes

Authors
 Yuhui Jeong  ;  Sun-Ho Lee  ;  Jangho Lee  ;  Min-Sun Kim  ;  Yu-Geon Lee  ;  Jin-Taek Hwang  ;  Sang-Yoon Choi  ;  Ho-Geun Yoon  ;  Tae-Gyu Lim  ;  Seung-Hyun Lee  ;  Hyo-Kyoung Choi 
Citation
 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol.24(21) : 15912, 2023-11 
Journal Title
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN
 1661-6596 
Issue Date
2023-11
MeSH
Animals ; Antioxidants / metabolism ; Apoptosis ; Breast Neoplasms* / metabolism ; Capsella* / metabolism ; Cardiotoxicity / drug therapy ; Cardiotoxicity / etiology ; Cardiotoxicity / metabolism ; Doxorubicin / metabolism ; Doxorubicin / toxicity ; Female ; Flavonoids / pharmacology ; Humans ; Mice ; Mice, Inbred C57BL ; Myocytes, Cardiac / metabolism ; Oxidative Stress ; Rats ; Reactive Oxygen Species / metabolism ; Superoxide Dismutase / metabolism
Keywords
Capsella bursa-pastoris ; doxorubicin-induced cardiotoxicity ; human-induced pluripotent stem-cell-derived cardiomyocytes ; mitochondrial dysfunction ; superoxide dismutase
Abstract
Doxorubicin (DOX), an effective chemotherapeutic drug, causes cardiotoxicity in a cumulative and dose-dependent manner. The aim of this study is to investigate the effects of hot-water extract of Capsella bursa-pastoris (CBW) on DOX-induced cardiotoxicity (DICT). We utilized H9c2 rat cardiomyocytes and MDA-MB-231 human breast cancer cells to evaluate the effects of CBW on DOX-induced cell death. Superoxide dismutase (SOD) levels, reactive oxygen species (ROS) production, and oxygen consumption rate were measured in H9c2 cells. C57BL/6 mice were treated with DOX and CBW to assess their impact on various cardiac parameters. Human-induced pluripotent stem-cell-derived cardiomyocytes were also used to investigate DOX-induced electrophysiological changes and the potential ameliorative effects of CBW. UPLC-TQ/MS analysis identified seven flavonoids in CBW, with luteolin-7-O-glucoside and isoorientin as the major compounds. CBW inhibited DOX-induced death of H9c2 rat cardiomyocytes but did not affect DOX-induced death of MDA-MB-231 human breast cancer cells. CBW increased SOD levels in a dose-dependent manner, reducing ROS production and increasing the oxygen consumption rate in H9c2 cells. The heart rate, RR interval, QT, and ST prolongation remarkably recovered in C57BL/6 mice treated with the combination of DOX and CBW compared to those in mice treated with DOX alone. Administration of CBW with DOX effectively alleviated collagen accumulation, cell death in mouse heart tissues, and reduced the levels of creatinine kinase (CK) and lactate dehydrogenase (LDH) in serum. Furthermore, DOX-induced pathological electrophysiological features in human-induced pluripotent stem-cell-derived cardiomyocytes were ameliorated by CBW. CBW may prevent DICT by stabilizing SOD and scavenging ROS. The presence of flavonoids, particularly luteolin-7-O-glucoside and isoorientin, in CBW may contribute to its protective effects. These results suggest the potential of CBW as a traditional therapeutic option to mitigate DOX-induced cardiotoxicity.
Files in This Item:
T202306281.pdf Download
DOI
10.3390/ijms242115912
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Yoon, Ho Geun(윤호근) ORCID logo https://orcid.org/0000-0003-2718-3372
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/196767
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