Salvianolic acid B promotes mitochondrial homeostasis and improves cardiac function in mice with ischemia-reperfusion injury by inhibiting Sirt1 protein degradation.
10.12122/j.issn.1673-4254.2025.10.02
- Author:
Simeng LI
1
;
Jianning CHEN
2
;
Siman SHEN
2
;
Wanglong LIU
2
;
Lili YU
1
;
Liangqing ZHANG
1
Author Information
1. Faculty of Chinese Medicine, Medical Sciences Division, Macau University of Science and Technology, Macau 999078, China.
2. Second Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China.
- Publication Type:Journal Article
- Keywords:
Sirt1;
heart;
mitochondrial homeostasis;
myocardial ischemia-reperfusion injury;
salvianolic acid B
- MeSH:
Animals;
Sirtuin 1/metabolism*;
Myocardial Reperfusion Injury/physiopathology*;
Mice, Inbred C57BL;
Mice;
Myocytes, Cardiac/drug effects*;
Benzofurans/pharmacology*;
Homeostasis/drug effects*;
Male;
Mitochondria/drug effects*;
Depsides
- From:
Journal of Southern Medical University
2025;45(10):2062-2070
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To investigate the molecular mechanism by which salvianolic acid B (Sal-B) modulates mitochondrial functional homeostasis and alleviates myocardial ischemia-reperfusion (I/R) injury in mice.
METHODS:Mouse cardiomyocyte HL-1 cells were pretreated with 5 μmol/L Sal-B with or without sh-Sirt1 transfection before exposure to hypoxia-reoxygenation (HR), and the changes in ATP production, mitochondrial superoxide activity, substrate oxidation level were evaluated. In the animal experiment, 36 C57BL/6J mice were randomized into 3 groups (n=12) for sham operation or ligation of the left anterior coronary artery to induce myocardial I/R injury with or without intravenous injection of Sal-B+I/R (50 mg/kg). In the rescue experiment, 60 adult C57BL/6J mice were randomized into 5 groups (n=12): sham-operated group, myocardial I/R group, Sal-B+I/R group, I/R+Sal-B+Sirt1fl/fl group, and I/R+Sal-B+cKO-Sirt1 group. Myocardial injury was evaluated with HE staining, and cardiac function was assessed by measurement of the ejection fraction and fractional shortening using echocardiography.
RESULTS:In HL-1 cells with HR injury, Sal-B pretreatment significantly increased cellular ATP production, reduced mitochondrial superoxide anion levels, and enhanced oxygen consumption level. In the mouse models of myocardial I/R injury, Sal-B pretreatment markedly ameliorated I/R-induced structural disarray of the cardiac myocytes and improved cardiac ejection. Cycloheximide chase with Western blotting and ubiquitination assays after Sirt1-IP showed that Sal-B significantly inhibited Sirt1 degradation in HL-1 cells. Sirt1 knock-down reversed Sal-B-induced increases in ATP production, reduction in superoxide, and elevation of OCR in HL-1 cells. Cardiomyocyte-specific Sirt1 knockout obviously reversed Sal-B-mediated improvement in cardiac ejection function and myocardial structure damage in mice with myocardial I/R injury.
CONCLUSIONS:Sal-B promotes mitochondrial functional homeostasis in cardiomyocytes with HR injury and improves cardiac function in mice after myocardial I/R by inhibiting Sirt1 protein degradation.
