Zishen Huoxue decoction (ZSHX) alleviates ischemic myocardial injury (MI) via Sirt5-β-tubulin mediated synergistic mechanism of "mitophagy-unfolded protein response" and mitophagy.
10.1016/S1875-5364(25)60838-7
- Author:
Xing CHANG
1
;
Siyuan ZHOU
1
;
Yu HUANG
1
;
Jinfeng LIU
1
;
Yanli WANG
1
;
Xuanke GUAN
1
;
Qiaomin WU
1
;
Zhiming LIU
2
,
3
;
Ruxiu LIU
3
,
4
Author Information
1. Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing,
2. Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053,. Electronic address: ZhimingLiuGAM@
3. com.
4. Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053,. Electronic address: liuruxiu1@
- Publication Type:Journal Article
- Keywords:
Mitochondrial oxidative stress;
Mitochondrial unfolded protein response;
Mitophagy;
Sirtuin 5;
Zishen Huoxue decoction;
β-Tubulin
- MeSH:
Mitophagy/drug effects*;
Tubulin/genetics*;
Animals;
Myocytes, Cardiac/metabolism*;
Drugs, Chinese Herbal/pharmacology*;
Sirtuins/genetics*;
Unfolded Protein Response/drug effects*;
Myocardial Ischemia/genetics*;
Rats;
Humans;
Rats, Sprague-Dawley;
Apoptosis/drug effects*;
Male
- From:
Chinese Journal of Natural Medicines (English Ed.)
2025;23(3):311-321
- CountryChina
- Language:English
-
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.
