Salvianolate injection ameliorates cardiomyopathy by regulating autophagic flux through miR-30a/becn1 axis in zebrafish.
10.1097/CM9.0000000000003322
- Author:
Jianxuan LI
1
;
Yang ZHANG
2
;
Zhi ZUO
3
;
Zhenzhong ZHANG
4
;
Ying WANG
2
;
Shufu CHANG
2
;
Jia HUANG
2
;
Yuxiang DAI
2
;
Junbo GE
1
Author Information
1. Department of Internal Medicine, Zhongshan Hospital, Fudan University, Shanghai 200030, China.
2. Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai 200030, China.
3. Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.
4. Shanghai Institute of Cardiovascular Diseases, Shanghai 200030, China.
- Publication Type:Journal Article
- Keywords:
Autophagy;
Azithromycin;
Cardiomyopathy;
Cardiotoxicity;
Doxorubicin;
Salvianolate;
becn1
- MeSH:
Animals;
Zebrafish;
MicroRNAs/genetics*;
Autophagy/drug effects*;
Myocytes, Cardiac/metabolism*;
Cardiomyopathies/metabolism*;
Beclin-1/genetics*;
Apoptosis/drug effects*;
Plant Extracts/therapeutic use*;
Doxorubicin
- From:
Chinese Medical Journal
2025;138(20):2604-2614
- CountryChina
- Language:English
-
Abstract:
BACKGROUND:Salvianolate is a compound mainly composed of salvia magnesium acetate, which is extracted from the Chinese herb Salvia miltiorrhiza . In recent years, salvianolate injection has been widely used in the treatment of cardiovascular diseases, but the mechanism of how it can alleviate cardiotoxicity remains unclear.
METHODS:The cardiac injury model was constructed by treatment with doxorubicin (Dox) or azithromycin (Azi) in zebrafish larvae. Heart phenotype, heart rate, and cardiomyocyte apoptosis were observed in the study. RNA-sequencing (RNA-seq) analysis was used to explore the underlying mechanism of salvianolate treatment. Moreover, cardiomyocyte autophagy was assessed by in situ imaging. In addition, the miR-30a/becn1 axis regulation by salvianolate was further investigated.
RESULTS:Salvianolate treatment reduced the proportion of pericardial edema, recovered heart rate, and inhibited cardiomyocyte apoptosis in Dox/Azi-administered zebrafish larvae. Mechanistically, salvianolate regulated the lysosomal pathway and promoted autophagic flux in zebrafish cardiomyocytes. The expression level of becn1 was increased in Dox-induced myocardial tissue injury after salvianolate administration; overexpression of becn1 in cardiomyocytes alleviated the Dox/Azi-induced cardiac injury and promoted autophagic flux in cardiomyocytes, while becn1 knockdown blocked the effects of salvianolate. In addition, miR-30a, negatively regulated by salvianolate, partially inhibited the cardiac amelioration of salvianolate by targeting becn1 directly.
CONCLUSION:This study has proved that salvianolate reduces cardiomyopathy by regulating autophagic flux through the miR-30a/becn1 axis in zebrafish and is a potential drug for adjunctive Dox/Azi therapy.
