Ginsenoside Rb1 alleviates uterine aging via AMPK-mediated mTOR inactivation
8 affiliations
- 1State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China
- 2Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, China
- 3Beijing Key Laboratory of Collaborative Innovation in Frontier Technologies for Population Quality, Beijing, China
- 4National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing, China
- 5National Clinical Key Specialty Construction Program, P.R. China (2023), Beijing, China
- 6Department of Medicine, Boston University School of Medicine, Boston, MA USA
- 7Clinical Stem Cell Research Center, Peking University Third Hospital, Beijing, China
- 8Beijing Advanced Center of Cellular Homeostasis and Aging-Related Diseases, Institute of Advanced Clinical Medicine, Peking University, Beijing, China
Abstract
Uterine aging impairs fertility and reproductive health, but the underlying pathogenic mechanisms and effective treatment strategies remain elusive. Defective endometrial decidualization and implantation failure are hallmarks of uterine aging, which can be driven by cellular senescence, especially in endometrial stromal cells (EnSCs). Rb1 has been reported to relieve cellular senescence by suppressing oxidative and inflammatory pathways. However, whether Rb1 functions in alleviating uterine aging remains uncertain. Here, we demonstrate that Rb1 can attenuate oxidative stress, senescence, and apoptosis in the EnSCs of the aging human endometrium and murine uterus. Further proteomic analysis reveals that Rb1 safeguards against endometrial aging by regulating mammalian target of rapamycin (mTOR)-related pathways. Rb1 treatment results in the activation of AMP-activated protein kinase (AMPK) and AMPK-mediated suppression of the mTOR-nuclear factor-kappa B (NF-κB) signaling loop, thereby ameliorating aging-related phenotypes. Collectively, our findings illustrate that Rb1 alleviates uterine aging by attenuating endometrial stromal cell senescence and suppressing AMPK–mTOR–NF-κB-driven inflammatory signaling. Rather than selectively eliminating senescent cells, Rb1 primarily targets senescence-associated dysfunction and restores endometrial homeostasis, highlighting its potential as a senescence-modulating therapeutic strategy for uterine aging.
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BibTeX
@article{zhou2026ginsenoside,
title = {{Ginsenoside Rb1 alleviates uterine aging via AMPK-mediated mTOR inactivation}},
author = {Ping Zhou and Yue Wang and Ming Cheng and Feng Deng and Fenting Liu and Xiunan Chen and Ke Ning and Dan Mo and Zhonghong Zeng and Ziying Huang and Yunshu Dong and Yinxue Wang and Chao Zhang and Jie Qiao and Yang Yu and Heng Pan and Rong Li},
journal = {Signal Transduction and Targeted Therapy},
year = {2026},
month = oct,
doi = {10.1038/s41392-026-02970-4},
url = {https://doi.org/10.1038/s41392-026-02970-4},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Ginsenoside Rb1 alleviates uterine aging via AMPK-mediated mTOR inactivation
AU - Ping Zhou
AU - Yue Wang
AU - Ming Cheng
AU - Feng Deng
AU - Fenting Liu
AU - Xiunan Chen
AU - Ke Ning
AU - Dan Mo
AU - Zhonghong Zeng
AU - Ziying Huang
AU - Yunshu Dong
AU - Yinxue Wang
AU - Chao Zhang
AU - Jie Qiao
AU - Yang Yu
AU - Heng Pan
AU - Rong Li
PY - 2026
DA - 2026/10/28
JO - Signal Transduction and Targeted Therapy
DO - 10.1038/s41392-026-02970-4
UR - https://doi.org/10.1038/s41392-026-02970-4
AB - Uterine aging impairs fertility and reproductive health, but the underlying pathogenic mechanisms and effective treatment strategies remain elusive. Defective endometrial decidualization and implantation failure are hallmarks of uterine aging, which can be driven by cellular senescence, especially in endometrial stromal cells (EnSCs). Rb1 has been reported to relieve cellular senescence by suppressing oxidative and inflammatory pathways. However, whether Rb1 functions in alleviating uterine aging remains uncertain. Here, we demonstrate that Rb1 can attenuate oxidative stress, senescence, and apoptosis in the EnSCs of the aging human endometrium and murine uterus. Further proteomic analysis reveals that Rb1 safeguards against endometrial aging by regulating mammalian target of rapamycin (mTOR)-related pathways. Rb1 treatment results in the activation of AMP-activated protein kinase (AMPK) and AMPK-mediated suppression of the mTOR-nuclear factor-kappa B (NF-κB) signaling loop, thereby ameliorating aging-related phenotypes. Collectively, our findings illustrate that Rb1 alleviates uterine aging by attenuating endometrial stromal cell senescence and suppressing AMPK–mTOR–NF-κB-driven inflammatory signaling. Rather than selectively eliminating senescent cells, Rb1 primarily targets senescence-associated dysfunction and restores endometrial homeostasis, highlighting its potential as a senescence-modulating therapeutic strategy for uterine aging.
SN - 2095-9907
SN - 2059-3635
ER -