Mechanism of cardamonin in inhibiting pulmonary fibroblast senescence through the mTOR-ROS axis
10.11665/j.issn.1000-5048.2025032601
- VernacularTitle:豆蔻明通过mTOR-ROS轴抑制肺成纤维细胞衰老的机制
- Author:
Ying LIU
1
;
Huixing LI
;
Qi SHAO
;
Yaoshuai ZHANG
;
Lei SUN
Author Information
1. 上海交通大学药学院, 上海 200240;创新免疫治疗全国重点实验室, 上海 200240;上海市药物靶标发现及递送前沿科学研究基地, 上海 200240
- Publication Type:Journal Article 期刊文章
- Keywords:
cardamonin;
senescence;
cellular senescence;
fibroblasts;
mTOR signaling pathway
- From:
Journal of China Pharmaceutical University
2025;56(5):592-600
- CountryChina
- Language:Chinese
-
Abstract:
Cardamonin, a natural flavonoid compound, exhibits potential anti-aging properties, yet its precise mechanisms still remain unclear. In this study, we established cellular senescence models using bleomycin and H2O2 and treated the cells with varying concentrations of cardamonin to investigate its anti-senescence effects and underlying mechanisms. Senescence-associated β-galactosidase (SA-β-gal) staining was employed to assess senescent phenotypes, while immunofluorescence was used to detect DNA damage levels. Intracellular reactive oxygen species (ROS) levels were measured using the DCFH-DA probe, and Western blot was performed to analyze the expression of p53, p21, collagen, α-smooth muscle actin (α-SMA), mechanistic target of rapamycin (mTOR), and p-mTOR. To further validate the mechanistic target, MHY1485 was utilized to activate the mTOR pathway and evaluate its regulatory impact on senescence phenotypes. The results demonstrated that cardamonin significantly alleviated bleomycin- and H2O2-induced cellular senescence. Mechanistic studies revealed that cardamonin reduced ROS accumulation and suppressed mTOR phosphorylation. Notably, MHY1485-mediated activation of the mTOR pathway reversed senescence and fibrotic phenotypes, providing reciprocal validation of the target mechanism. In conclusion, cardamonin mitigates cellular senescence by targeting the mTOR-ROS axis, offering a promising therapeutic strategy for anti-aging interventions and the treatment of idiopathic pulmonary fibrosis (IPF).
