Astragaloside Ⅳ alleviates D-galactose-induced cardiomyocytes senescence and apoptosis by inhibiting the STING pathway
10.11714/jsysu.med.YX20250094
- VernacularTitle:黄芪甲苷通过抑制STING通路减轻D-半乳糖诱导的心肌细胞衰老和凋亡
- Author:
Wenyu GUO
1
;
Jiajia GAO
1
;
Weili DUAN
1
;
Huanjun RUAN
1
;
Yulang HUANG
2
;
Kemei WANG
1
;
Xiao KE
1
Author Information
1. Department of Cardiology， Fuwai Hospital， Chinese Academy of Medical Sciences， Shenzhen 518057， China
2. Department of Cardiology， Shenzhen Qianhai Shekou Free Trade Zone Hospital， Shenzhen 518067， China
- Publication Type:Journal Article
- Keywords:
Astragaloside Ⅳ;
D-galactose;
STING pathway;
cardiomyocytes;
senescence
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2026;47(1):133-142
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the protective effect of Astragaloside Ⅳ （AS-Ⅳ） on D-galactose （D-gal）-induced cardiomyocytes senescence and its potential mechanisms. MethodsUsing H9C2 cardiomyocytes as a model， D-gal was used to induce cardiomyocyte senescence. Cell viability was assessed using the CCK-8 assay， senescenceextent was evaluated via β-galactosidase （SA-β-Gal） staining， reactive oxygen species （ROS） levels were measured to assess intracellular oxidative stress， apoptosis extent was determined using the TUNEL assay， and qRT-PCR and Western blot analyses were conducted to examine the expression levels of senescence-related genes and proteins （p21、p53） and key genes （STING， CXCL10， and MX-1） and proteins （STING， cGAS， p-IRF3/IRF3） of the stimulator of interferon genes （STING） pathway. ResultsThe 50 g/L D-gal significantly reduced myocardial cell viability， increased SA-β-Gal positivity， apoptosis rate， and intracellular reactive oxygen species levels， and upregulated the expression of p16， p21， and STING， cGAS， p-IRF3/IRF3 pathway proteins （P< 0.05）； After intervention with 200 μmol/L of AS-Ⅳ， cell viability was significantly enhanced， the SA-β-Gal-positive rate decreased， intracellular reactive oxygen species levels decreased， oxidative stress damage was alleviated， myocardial cell apoptosis was inhibited， and the mRNA and protein levels of aging-related p21 and p53 were downregulated （P＜0.05）. Further detection of STING pathway-related molecules showed that 200 μmol/L of AS-IV inhibited D-galactose-induced STING mRNA and protein expression and reduced p-IRF3/IRF3 protein expression levels， as demonstrated by qRT-PCR and Western blot results. However， the SA-β-Gal positivity rate， intracellular reactive oxygen species （ROS） levels， DNA damage results， and Western blot findings suggested that the STING agonist （STING agonist-7） could reverse the ameliorative effects of AS-Ⅳ on D-galactose-induced cardiomyocytes senescence. ConclusionAS-Ⅳ may mitigate D-gal-induced cardiomyocytes senescence by inhibiting STING pathway activation， providinga new strategy for the prevention and treatment of cardiovascular senescence-related diseases.
