Hydroxysafflor Yellow A Ameliorates the Replicative Senescence of Human Umbilical Cord Mesenchymal Stem Cells by Suppressing Oxidative Stress.
10.19746/j.cnki.issn.1009-2137.2025.05.039
- Author:
Si-Yun WANG
1
;
Qi ZHU
1
;
Chun-Xia TAN
1
;
Fang LU
1
;
Tao LU
1
Author Information
1. School of Life Science, Beijing University of Chinese Medicine, Beijing 102488, China.
- Publication Type:Journal Article
- Keywords:
hydroxysafflor yellow A;
human umbilical cord mesenchymal stem cell;
senescence;
oxidative stress
- MeSH:
Humans;
Mesenchymal Stem Cells/drug effects*;
Cellular Senescence/drug effects*;
Chalcone/pharmacology*;
Oxidative Stress/drug effects*;
Quinones/pharmacology*;
Umbilical Cord/cytology*;
Reactive Oxygen Species/metabolism*;
Cells, Cultured;
Cyclin-Dependent Kinase Inhibitor p16/metabolism*;
Tumor Suppressor Protein p53/metabolism*;
Membrane Potential, Mitochondrial;
Cell Proliferation
- From:
Journal of Experimental Hematology
2025;33(5):1507-1515
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the effects and mechanisms of hydroxysafflor yellow A (HSYA) on replicative senescence in human umbilical cord mesenchymal stem cells (hUC-MSCs).
METHODS:hUC-MSCs were cultured to construct a replicative senescence model through continuous amplification in vitro. Cells at passage 2 served as the control group, while cells at passage 10 were designated as the senescence group. The senescent cells were cultured in a culture medium containing HSYA. Cell viability was detected by the CCK-8 assay, and cell confluence was analyzed using the Incucyte S3 live-cell analysis system. The optimal concentration and time point were determined and utilized for subsequent experiments. Senescent cells were pretreated with 0.01 mg/ml HSYA, and the proportion of senescence-associated β-galactosidase (SA-β-gal) positive cells was detected to assess the senescence state. The relative telomere length was detected by qPCR. Reactive oxygen species (ROS) levels were measured using the fluorescent probe DCFH-DA. Mitochondrial membrane potential was assessed by JC-1 staining. The expression of p53, p16, p21, OCT4, and SOX2 genes was detected by qPCR. The expression of p16, p53, OCT4, and SOX2 proteins was analyzed by Western blot.
RESULTS:HSYA significantly decreased the SA-β-gal positive staining rate, inhibited telomere attrition, reduced the ROS accumulation, increased mitochondrial membrane potential in senescent cells. Additionally, HSYA downregulated the expression of p53 and p16, and upregulated the expression of OCT4. HSYA decreased p16 protein level and increased OCT4 and SOX2 protein levels.
CONCLUSION:HSYA may ameliorate replicative senescence in hUC-MSCs by modulating the p53 and p16 signaling pathways and suppressing oxidative stress.
