PUBLICATION
Multi-Target Botanical Complex Attenuates Cellular Senescence via Bidirectional P21/P53/SIRT1 Regulation: Dual Model Validation
- Authors
- Wu, J., Dongzhu, N., Zhao, C., Liang, J., Wang, N., Suonan, D., Sun, S.
- ID
- ZDB-PUB-251211-11
- Date
- 2025
- Source
- International Journal of Molecular Sciences 26: (Journal)
- Registered Authors
- Keywords
- P21/P53/SIRT1 axis, apoptosis, bidirectional regulation, botanical complex, cardiomyocytes, cellular senescence, multi-target, senotherapeutics, zebrafish model
- MeSH Terms
-
- Animals
- Antioxidants/pharmacology
- Apoptosis/drug effects
- Cell Line
- Cell Survival/drug effects
- Cellular Senescence*/drug effects
- Cyclin-Dependent Kinase Inhibitor p21*/genetics
- Cyclin-Dependent Kinase Inhibitor p21*/metabolism
- Galactose
- Hydrogen Peroxide
- Myocytes, Cardiac/drug effects
- Myocytes, Cardiac/metabolism
- Oxidative Stress/drug effects
- Plant Extracts*/pharmacology
- Rats
- Signal Transduction/drug effects
- Sirtuin 1*/genetics
- Sirtuin 1*/metabolism
- Tumor Suppressor Protein p53*/genetics
- Tumor Suppressor Protein p53*/metabolism
- Zebrafish
- PubMed
- 41373554 Full text @ Int. J. Mol. Sci.
Citation
Wu, J., Dongzhu, N., Zhao, C., Liang, J., Wang, N., Suonan, D., Sun, S. (2025) Multi-Target Botanical Complex Attenuates Cellular Senescence via Bidirectional P21/P53/SIRT1 Regulation: Dual Model Validation. International Journal of Molecular Sciences. 26:.
Abstract
Cellular senescence is a pivotal driver of aging and age-related diseases. This study aims to systematically investigate the anti-senescence effects and molecular mechanisms of a multi-component botanical complex (SBT) using both a D-galactose-induced senescence model in H9c2 cardiomyocytes and an H2O2-induced accelerated aging model in zebrafish. The SBT complex comprises Solms-laubachia eurycarpa, Bergenia purpurascens, Laccifer lacca, and Glycyrrhiza uralensis. Results demonstrated that SBT treatment significantly enhanced cell viability (increased from 52% to 85%) and reduced senescence-associated β-galactosidase (SA-β-gal) activity (from 41.2% to 20%). At the molecular level, SBT exerted bidirectional regulation of the P21/P53/SIRT1 axis, coordinately downregulating the pro-senescence proteins P53 and P21 while upregulating the longevity-associated deacetylase SIRT1. It also modulated the balance of apoptosis-related genes by suppressing Bax and enhancing Bcl-2 expression. In the zebrafish model, SBT significantly strengthened the antioxidant defense system, as indicated by increased activities of superoxide dismutase (SOD) and catalase (CAT), elevated glutathione (GSH) levels, and reduced malondialdehyde (MDA) content. These findings confirm that SBT exerts potent anti-senescence effects through bidirectional regulation of the P21/P53/SIRT1 signaling axis, enhanced antioxidant capacity, and inhibition of apoptosis, thereby providing a mechanistic foundation for the development of natural product-based interventions against aging and related diseases.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping