Echinacoside ameliorates doxorubicin‑induced cardiac injury by regulating GPX4 inhibition‑induced ferroptosis.

IF 2.4 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Experimental and therapeutic medicine Pub Date : 2023-11-23 DOI:10.3892/etm.2023.12317
Yan Ma, Xiaoli Yang, Nianxin Jiang, Cheng Lu, Jiehan Zhang, Shaowei Zhuang
{"title":"Echinacoside ameliorates doxorubicin‑induced cardiac injury by regulating GPX4 inhibition‑induced ferroptosis.","authors":"Yan Ma, Xiaoli Yang, Nianxin Jiang, Cheng Lu, Jiehan Zhang, Shaowei Zhuang","doi":"10.3892/etm.2023.12317","DOIUrl":null,"url":null,"abstract":"Echinacoside (ECH) is a compound derived from the natural herbs <i>Cistanche</i> and <i>Echinacea</i>, which has considerable protective effects on heart failure (HF). HF is characterized by myocardial damage and abnormal ferroptosis. Glutathione peroxidase 4 (GPX4) is an important regulator of ferroptosis, which plays a role in ferroptosis-related diseases. Despite this, the therapeutic mechanisms of ECH against HF remain unknown. Therefore, the aim of the present study was to investigate the cardioprotective effect and underlying mechanisms of ECH in the treatment of doxorubicin (DOX)-induced chronic HF (CHF). Cell proliferation was assessed using a CCK-8 assay. Furthermore, cardiac cell injury and oxidative stress were determined by measuring the lactate dehydrogenase (LDH), malondialdehyde (MDA), and glutathione (GSH) levels. The levels of Fe<sup>2+</sup> and lipid reactive oxygen species (ROS), and expression of the biomarkers of ferroptosis, including GPX4 and prostaglandin-endoperoxide synthase 2 (PTGS2), were measured to examine cardiomyocyte ferroptosis. Additionally, RNA interference was used to silence <i>Gpx4</i>. <i>In vitro</i> and <i>in vivo</i>, ECH considerably reduced the MDA and LDH levels and increased the GSH level, thereby attenuating DOX-induced cardiac injury and oxidative stress. Meanwhile, ECH treatment decreased the lipid ROS levels and PTGS2 expression while increasing GPX4 expression, thereby alleviating DOX-induced cardiomyocyte ferroptosis. Moreover, knockdown of <i>Gpx4</i> inhibited the protective effects of ECH on DOX-induced accumulation of lipid ROS in cardiomyocytes. These findings indicate that ECH can reduce DOX-induced cardiac injury by inhibiting ferroptosis via GPX4, highlighting its value as a potentially valuable therapeutic target in the management of CHF.","PeriodicalId":12285,"journal":{"name":"Experimental and therapeutic medicine","volume":"128 1","pages":""},"PeriodicalIF":2.4000,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Experimental and therapeutic medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3892/etm.2023.12317","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0

Abstract

Echinacoside (ECH) is a compound derived from the natural herbs Cistanche and Echinacea, which has considerable protective effects on heart failure (HF). HF is characterized by myocardial damage and abnormal ferroptosis. Glutathione peroxidase 4 (GPX4) is an important regulator of ferroptosis, which plays a role in ferroptosis-related diseases. Despite this, the therapeutic mechanisms of ECH against HF remain unknown. Therefore, the aim of the present study was to investigate the cardioprotective effect and underlying mechanisms of ECH in the treatment of doxorubicin (DOX)-induced chronic HF (CHF). Cell proliferation was assessed using a CCK-8 assay. Furthermore, cardiac cell injury and oxidative stress were determined by measuring the lactate dehydrogenase (LDH), malondialdehyde (MDA), and glutathione (GSH) levels. The levels of Fe2+ and lipid reactive oxygen species (ROS), and expression of the biomarkers of ferroptosis, including GPX4 and prostaglandin-endoperoxide synthase 2 (PTGS2), were measured to examine cardiomyocyte ferroptosis. Additionally, RNA interference was used to silence Gpx4. In vitro and in vivo, ECH considerably reduced the MDA and LDH levels and increased the GSH level, thereby attenuating DOX-induced cardiac injury and oxidative stress. Meanwhile, ECH treatment decreased the lipid ROS levels and PTGS2 expression while increasing GPX4 expression, thereby alleviating DOX-induced cardiomyocyte ferroptosis. Moreover, knockdown of Gpx4 inhibited the protective effects of ECH on DOX-induced accumulation of lipid ROS in cardiomyocytes. These findings indicate that ECH can reduce DOX-induced cardiac injury by inhibiting ferroptosis via GPX4, highlighting its value as a potentially valuable therapeutic target in the management of CHF.
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
紫锥栗苷通过调节 GPX4 抑制诱导的铁氧化作用来改善多柔比星诱导的心脏损伤
紫锥菊苷(ECH)是从天然草药肉苁蓉和紫锥菊中提取的一种化合物,对心力衰竭(HF)有相当大的保护作用。心力衰竭的特点是心肌损伤和铁蛋白沉积异常。谷胱甘肽过氧化物酶 4(GPX4)是铁变态反应的重要调节因子,在铁变态反应相关疾病中发挥着作用。尽管如此,ECH 对高血压的治疗机制仍然未知。因此,本研究旨在探讨 ECH 在治疗多柔比星(DOX)诱导的慢性心房颤动(CHF)中的心脏保护作用及其内在机制。细胞增殖采用 CCK-8 试验进行评估。此外,还通过测量乳酸脱氢酶(LDH)、丙二醛(MDA)和谷胱甘肽(GSH)的水平来确定心脏细胞损伤和氧化应激。通过测量铁2+和脂质活性氧(ROS)的水平以及铁变态反应生物标志物(包括GPX4和前列腺素内过氧化物合成酶2(PTGS2))的表达来研究心肌细胞的铁变态反应。此外,还使用 RNA 干扰来抑制 Gpx4。在体外和体内,ECH显著降低了MDA和LDH水平,提高了GSH水平,从而减轻了DOX诱导的心脏损伤和氧化应激。同时,ECH 还能降低脂质 ROS 水平和 PTGS2 的表达,同时增加 GPX4 的表达,从而缓解 DOX 诱导的心肌细胞铁变态反应。此外,Gpx4 的敲除抑制了 ECH 对 DOX 诱导的心肌细胞脂质 ROS 累积的保护作用。这些研究结果表明,ECH可通过GPX4抑制铁卟啉沉积,从而减轻DOX诱导的心脏损伤,突出了其作为治疗慢性心力衰竭的潜在治疗靶点的价值。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Experimental and therapeutic medicine
Experimental and therapeutic medicine MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
1.50
自引率
0.00%
发文量
570
审稿时长
1 months
期刊介绍:
期刊最新文献
Off‑label and unapproved pediatric drug utilization: A meta‑analysis. Multivariate analysis of blood parameters for predicting mortality in patients with hip fractures. New insights on the link between Epstein‑Barr virus infection and cognitive decline in neurodegenerative diseases (Review). Peptic ulcer induced by immune checkpoint inhibitors successfully treated with glucocorticoids: A report of three cases and a literature review. Different strategies for treating intracanal fractured instruments in a single tooth: A case report.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1