Zishen Huoxue decoction (ZSHX) alleviates ischemic myocardial injury (MI) via Sirt5-β-tubulin mediated synergistic mechanism of “mitophagy-unfolded protein response” and mitophagy

IF 4 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE
Xing Chang , Siyuan Zhou , Yu Huang , Jinfeng Liu, Yanli Wang, Xuanke Guan, Qiaomin Wu, Zhiming Liu, Ruxiu Liu
{"title":"Zishen Huoxue decoction (ZSHX) alleviates ischemic myocardial injury (MI) via Sirt5-β-tubulin mediated synergistic mechanism of “mitophagy-unfolded protein response” and mitophagy","authors":"Xing Chang ,&nbsp;Siyuan Zhou ,&nbsp;Yu Huang ,&nbsp;Jinfeng Liu,&nbsp;Yanli Wang,&nbsp;Xuanke Guan,&nbsp;Qiaomin Wu,&nbsp;Zhiming Liu,&nbsp;Ruxiu Liu","doi":"10.1016/S1875-5364(25)60838-7","DOIUrl":null,"url":null,"abstract":"<div><div>Zishen Huoxue decoction (ZSHX) enhances cardiomyocyte viability following hypoxic stress; however, its upstream therapeutic targets remain unclear. Network pharmacology and RNA sequencing analyses revealed that ZSHX target genes were closely associated with mitophagy and apoptosis in the mitochondrial pathway. <em>In vitro</em>, ZSHX inhibited pathological mitochondrial fission following hypoxic stress, regulated FUN14 domain-containing protein 1 (FUNDC1)-related mitophagy, and increased the levels of mitophagy lysosomes and microtubule-associated protein 1 light chain 3 beta II (LC3II)/translocase of outer mitochondrial membrane 20 (TOM20) expression while inhibiting the over-activated mitochondrial unfolded protein response. Additionally, ZSHX regulated the stability of beta-tubulin through Sirtuin 5 (SIRT5) and could modulate FUNDC1-related synergistic mechanisms of mitophagy and unfolded protein response in the mitochondria (UPR<sup>mt</sup>) <em>via</em> the SIRT5 and -<em>β</em>-tubulin axis. This targeting pathway may be crucial for cardiomyocytes to resist hypoxia. Collectively, these findings suggest that ZSHX can protect against cardiomyocyte injury <em>via</em> the SIRT5-<em>β</em>-tubulin axis, which may be associated with the synergistic protective mechanism of SIRT5-<em>β</em>-tubulin axis-related mitophagy and UPR<sup>mt</sup> on cardiomyocytes.</div></div>","PeriodicalId":10002,"journal":{"name":"Chinese Journal of Natural Medicines","volume":"23 3","pages":"Pages 311-321"},"PeriodicalIF":4.0000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chinese Journal of Natural Medicines","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1875536425608387","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"INTEGRATIVE & COMPLEMENTARY MEDICINE","Score":null,"Total":0}
引用次数: 0

Abstract

Zishen Huoxue decoction (ZSHX) enhances cardiomyocyte viability following hypoxic stress; however, its upstream therapeutic targets remain unclear. Network pharmacology and RNA sequencing analyses revealed that ZSHX target genes were closely associated with mitophagy and apoptosis in the mitochondrial pathway. In vitro, ZSHX inhibited pathological mitochondrial fission following hypoxic stress, regulated FUN14 domain-containing protein 1 (FUNDC1)-related mitophagy, and increased the levels of mitophagy lysosomes and microtubule-associated protein 1 light chain 3 beta II (LC3II)/translocase of outer mitochondrial membrane 20 (TOM20) expression while inhibiting the over-activated mitochondrial unfolded protein response. Additionally, ZSHX regulated the stability of beta-tubulin through Sirtuin 5 (SIRT5) and could modulate FUNDC1-related synergistic mechanisms of mitophagy and unfolded protein response in the mitochondria (UPRmt) via the SIRT5 and -β-tubulin axis. This targeting pathway may be crucial for cardiomyocytes to resist hypoxia. Collectively, these findings suggest that ZSHX can protect against cardiomyocyte injury via the SIRT5-β-tubulin axis, which may be associated with the synergistic protective mechanism of SIRT5-β-tubulin axis-related mitophagy and UPRmt on cardiomyocytes.
求助全文
约1分钟内获得全文 求助全文
来源期刊
Chinese Journal of Natural Medicines
Chinese Journal of Natural Medicines INTEGRATIVE & COMPLEMENTARY MEDICINE-PHARMACOLOGY & PHARMACY
CiteScore
7.50
自引率
4.30%
发文量
2235
期刊介绍: The Chinese Journal of Natural Medicines (CJNM), founded and sponsored in May 2003 by China Pharmaceutical University and the Chinese Pharmaceutical Association, is devoted to communication among pharmaceutical and medical scientists interested in the advancement of Traditional Chinese Medicines (TCM). CJNM publishes articles relating to a broad spectrum of bioactive natural products, leading compounds and medicines derived from Traditional Chinese Medicines (TCM). Topics covered by the journal are: Resources of Traditional Chinese Medicines; Interaction and complexity of prescription; Natural Products Chemistry (including structure modification, semi-and total synthesis, bio-transformation); Pharmacology of natural products and prescription (including pharmacokinetics and toxicology); Pharmaceutics and Analytical Methods of natural products.
×
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
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
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 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信