The Chinese Herbal Medicine Li Qi Huo Xue Di Wan Ameliorates Ischemia or Hypoxia‐Induced Cardiac Injury and Remodeling in the Heart Through a Mechanism Involving Reduction of Necroptosis

IF 4.4 3区 医学 Q2 ENVIRONMENTAL SCIENCES Environmental Toxicology Pub Date : 2024-11-12 DOI:10.1002/tox.24435
Yi‐Yue Zhang, Can Tang, Ya‐Qi Dou, Xiu‐Ju Luo, Jian Pu, Jun Peng
{"title":"The Chinese Herbal Medicine Li Qi Huo Xue Di Wan Ameliorates Ischemia or Hypoxia‐Induced Cardiac Injury and Remodeling in the Heart Through a Mechanism Involving Reduction of Necroptosis","authors":"Yi‐Yue Zhang, Can Tang, Ya‐Qi Dou, Xiu‐Ju Luo, Jian Pu, Jun Peng","doi":"10.1002/tox.24435","DOIUrl":null,"url":null,"abstract":"Li Qi Huo Xue Di Wan (LQHXDW), a Chinese herbal medicine, is commonly used to treat symptoms such as palpitations, chest tightness, chest pain, and shortness of breath. However, its potential to reduce ischemia or hypoxia‐induced cardiac injury and remodeling, along with the precise mechanisms involved, remains unclear. This study aims to investigate the effects of LQHXDW on cardiac injury and remodeling induced by ischemia or hypoxia, both in vivo and in vitro, and to elucidate the underlying mechanisms. The mouse heart was subjected to ischemia for 14 days, showing evident myocardial injury and notable cardiac remodeling, accompanied by a reduction in cardiac function; these phenomena were reversed in the presence of LQHXDW. In the cultured cardiomyocyte exposed to hypoxia, incubation with LQHXDW increased the cell viability and reduced lactate dehydrogenase release. Mechanistically, LQHXDW exerted inhibitory effect on the phosphorylation levels of RIPK1, RIPK3, and MLKL as well as oxidative stress in the mice hearts suffered ischemia and the cultured cardiomyocytes exposed to hypoxia. Using the methods of ultra‐high performance liquid chromatography‐quadrupole time‐of‐flight‐mass spectrometry, network pharmacology, and cellular thermal shift assay, phenethyl caffeate and isoliquiritigenin were identified as the potential active compounds in LQHXDW that counteract necroptosis. Based on these observations, we conclude that LQHXDW protects the heart against ischemia or hypoxia‐induced cardiac injury and remodeling through suppression of the RIPK1/RIPK3/MLKL pathway‐dependent necroptosis and oxidative stress.","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":null,"pages":null},"PeriodicalIF":4.4000,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Environmental Toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/tox.24435","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENVIRONMENTAL SCIENCES","Score":null,"Total":0}
引用次数: 0

Abstract

Li Qi Huo Xue Di Wan (LQHXDW), a Chinese herbal medicine, is commonly used to treat symptoms such as palpitations, chest tightness, chest pain, and shortness of breath. However, its potential to reduce ischemia or hypoxia‐induced cardiac injury and remodeling, along with the precise mechanisms involved, remains unclear. This study aims to investigate the effects of LQHXDW on cardiac injury and remodeling induced by ischemia or hypoxia, both in vivo and in vitro, and to elucidate the underlying mechanisms. The mouse heart was subjected to ischemia for 14 days, showing evident myocardial injury and notable cardiac remodeling, accompanied by a reduction in cardiac function; these phenomena were reversed in the presence of LQHXDW. In the cultured cardiomyocyte exposed to hypoxia, incubation with LQHXDW increased the cell viability and reduced lactate dehydrogenase release. Mechanistically, LQHXDW exerted inhibitory effect on the phosphorylation levels of RIPK1, RIPK3, and MLKL as well as oxidative stress in the mice hearts suffered ischemia and the cultured cardiomyocytes exposed to hypoxia. Using the methods of ultra‐high performance liquid chromatography‐quadrupole time‐of‐flight‐mass spectrometry, network pharmacology, and cellular thermal shift assay, phenethyl caffeate and isoliquiritigenin were identified as the potential active compounds in LQHXDW that counteract necroptosis. Based on these observations, we conclude that LQHXDW protects the heart against ischemia or hypoxia‐induced cardiac injury and remodeling through suppression of the RIPK1/RIPK3/MLKL pathway‐dependent necroptosis and oxidative stress.
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
中药六味地黄丸通过减少坏死机制改善缺血缺氧诱导的心脏损伤和重塑
六味地黄丸(LQHXDW)是一种中药,常用于治疗心悸、胸闷、胸痛和气短等症状。然而,它在减轻缺血或缺氧引起的心脏损伤和重塑方面的潜力及其确切机制仍不清楚。本研究旨在探讨 LQHXDW 在体内和体外对缺血或缺氧诱导的心脏损伤和重构的影响,并阐明其潜在机制。小鼠心脏缺血 14 天后出现明显的心肌损伤和心脏重塑,并伴有心功能减退;LQHXDW 的存在可逆转这些现象。在缺氧条件下培养的心肌细胞中,与 LQHXDW 一起孵育可提高细胞活力并减少乳酸脱氢酶的释放。从机理上讲,LQHXDW对缺血小鼠心脏和缺氧培养心肌细胞中RIPK1、RIPK3和MLKL的磷酸化水平以及氧化应激均有抑制作用。通过超高效液相色谱-四极杆飞行时间质谱法、网络药理学和细胞热转移分析等方法,我们发现咖啡酸苯乙酯和异桔梗素是 LQHXDW 中潜在的能对抗坏死的活性化合物。基于这些观察结果,我们得出结论:LQHXDW 通过抑制依赖于 RIPK1/RIPK3/MLKL 通路的坏死和氧化应激,保护心脏免受缺血或缺氧引起的心脏损伤和重塑。
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
Environmental Toxicology
Environmental Toxicology 环境科学-毒理学
CiteScore
7.10
自引率
8.90%
发文量
261
审稿时长
4.5 months
期刊介绍: The journal publishes in the areas of toxicity and toxicology of environmental pollutants in air, dust, sediment, soil and water, and natural toxins in the environment.Of particular interest are: Toxic or biologically disruptive impacts of anthropogenic chemicals such as pharmaceuticals, industrial organics, agricultural chemicals, and by-products such as chlorinated compounds from water disinfection and waste incineration; Natural toxins and their impacts; Biotransformation and metabolism of toxigenic compounds, food chains for toxin accumulation or biodegradation; Assays of toxicity, endocrine disruption, mutagenicity, carcinogenicity, ecosystem impact and health hazard; Environmental and public health risk assessment, environmental guidelines, environmental policy for toxicants.
期刊最新文献
The Chinese Herbal Medicine Li Qi Huo Xue Di Wan Ameliorates Ischemia or Hypoxia‐Induced Cardiac Injury and Remodeling in the Heart Through a Mechanism Involving Reduction of Necroptosis MCM4 Promotes the Progression of Malignant Melanoma by Activating the PI3K/AKT Pathway. SERPING1 Reduces Cell Migration via ERK-MMP2-MMP-9 Cascade in Sorafenib- Resistant Hepatocellular Carcinoma. Correction to "Inflammatory Response and Endothelial Dysfunction in the Hearts of Mice Co-Exposed to SO2, NO2, and PM2.5". Increased Susceptibility of Cardiac Tissue to PM2.5-Induced Toxicity in Uremic Cardiomyopathic Rats Is Linked to Elevated Levels of Mitochondrial Dysfunction.
×
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