Page 60 - 《中国药科大学学报》2025年第5期

学报
592 Journal of China Pharmaceutical University 2025, 56(5): 592 − 600

豆蔻明通过 mTOR-ROS 轴抑制肺成纤维细胞衰老的机制

刘 颖 1,2,3 ，李慧星 1,2,3 ，邵 琦 1,2,3 ，张耀帅 1,2,3 ，孙 磊 1,2,3*

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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）
3
摘 要 豆蔻明（cardamonin）是一种具有抗衰老潜力的天然黄酮类化合物，但其抗衰老的具体作用机制尚不明确。本研究
通过博来霉素（bleomycin）和过氧化氢（H 2 O 2 ）分别诱导细胞衰老模型，并用不同浓度的豆蔻明处理细胞，探讨豆蔻明的
抗衰老作用和机制。采用衰老相关 β-半乳糖苷酶（senescence-associated β-galactosidase, SA-β-gal）染色检测衰老表型；免疫
荧光检测 DNA 损伤水平；DCFH-DA 探针检测细胞内活性氧（reactive oxygen species, ROS）水平；Western blot 分析 p53、
p21、胶原蛋白、α-平滑肌肌动蛋白（α-SMA）、哺乳动物雷帕霉素靶蛋白（mechanistic target of rapamycin, mTOR）和 p-
mTOR 蛋白表达；利用 MHY1485 激活 mTOR 通路反向验证其对衰老表型的调控作用。实验结果显示豆蔻明能显著缓解博
来霉素和 H 2 O 2 诱导的细胞衰老表型，机制研究表明豆蔻明能降低 ROS 水平并抑制 mTOR 的磷酸化；MHY1485 激活
mTOR 通路可恢复细胞衰老和纤维化表型，反向验证其机制靶点。总的来说，豆蔻明通过 mTOR-ROS 轴缓解细胞衰老，为抗
衰老药物开发及特发性肺纤维化（idiopathic pulmonary fibrosis, IPF）治疗提供了潜在策略。
关键词 豆蔻明；衰老；细胞衰老；成纤维细胞；mTOR 信号通路
中图分类号 R965 文献标志码 A 文章编号 1000−5048(2025)05−0592−09
doi：10.11665/j.issn.1000−5048.2025032601

引用本文 刘颖，李慧星，邵琦，等. 豆蔻明通过 mTOR-ROS 轴抑制肺成纤维细胞衰老的机制 [J]. 中国药科大学学报，2025，56（5）：
592 − 600.

Cite this article as: LIU Ying, LI Huixing, SHAO Qi, et al. Mechanism of cardamonin in inhibiting pulmonary fibroblast senescence through
the mTOR-ROS axis[J]. J China Pharm Univ, 2025, 56(5): 592 − 600.

Mechanism of cardamonin in inhibiting pulmonary fibroblast senescence

through the mTOR-ROS axis
LIU Ying 1,2,3 , LI Huixing 1,2,3 , SHAO Qi 1,2,3 , ZHANG Yaoshuai 1,2,3 , SUN Lei 1,2,3*
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School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240; State Key Laboratory of Innovative Immunotherapy;
3
Shanghai 200240; Shanghai Frontier Research Base for Drug Target Discovery and Delivery, Shanghai 200240, China

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
H O and treated the cells with varying concentrations of cardamonin to investigate its anti-senescence effects
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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 H O -induced cellular senescence. Mechanistic studies revealed that
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cardamonin reduced ROS accumulation and suppressed mTOR phosphorylation. Notably, MHY1485-mediated

收稿日期 2025-03-26 * 通信作者 Tel：021-34207424 E-mail：sunlei_vicky@sjtu.edu.cn
基金项目 国家自然科学基金项目（No.82273934;No.82473928）