Ginsenoside Rg2 attenuates TGF-β1/Smad-mediated fibrotic remodeling in aged male mice with sarcopenia
5 affiliations
- 1Guangzhou University of Chinese Medicine, Guangzhou, 510006, China; The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
- 2Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
- 3Guangzhou Medical University, Guangzhou, 511436, China; The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, China
- 4The Affiliated TCM Hospital of Guangzhou Medical University, Guangzhou, 510130, China
- 5Guangzhou Medical University, Guangzhou, 511436, China; The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, China; Corresponding author. The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, China.
Abstract
Background: Sarcopenia is an age-related degenerative disease often accompanied by chronic low-grade inflammation and fibrotic remodeling, yet its specific underlying mechanisms remain unclear. This study aimed to explore the potential mechanism by which ginsenoside Rg2 ameliorates aging-related sarcopenia, with particular attention to TGF-β1/Smad-mediated fibrosis. Methods: Using single-cell sequencing, transcriptomic analysis, and Mendelian randomization (MR), we identified a causal relationship between transforming growth factor-β1 (TGF-β1)-mediated fibrosis and the progression of sarcopenia. We employed siRNA-mediated gene knockdown, real-time quantitative polymerase chain reaction (RT-qPCR), grip strength testing, western blotting, histological staining, molecular docking, molecular dynamics simulation, surface plasmon resonance (SPR), cellular thermal shift assay (CETSA), and drug affinity responsive target stability (DARTS) assays to evaluate the effects and potential mechanisms of Rg2 in aged male mice and C2C12 cell models. Results: Single-cell sequencing and MR analyses revealed that aging was associated with depletion of muscle satellite cells and skeletal muscle cells, together with increased neutrophils and fibroblasts. TGF-β1-related signaling showed a genetically supported association with sarcopenia-related traits and was closely associated with fibrotic remodeling in aged skeletal muscle. Rg2 treatment significantly mitigated age-associated weight gain while improving muscle mass, strength, and exercise endurance. Mechanistically, Rg2 interacted with TGF-β1 and attenuated downstream Smad2/3 phosphorylation in vitro and in vivo, thereby modulating inflammatory and fibrosis-related markers and partially reversing muscle tissue and cellular senescence. Conclusion: Our findings suggest that ginsenoside Rg2 alleviates TGF-β1/Smad-mediated fibrotic remodeling and improves the aging-related inflammatory-fibrotic microenvironment during skeletal muscle aging.
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BibTeX
@article{liu2026ginsenoside,
title = {{Ginsenoside Rg2 attenuates TGF-β1/Smad-mediated fibrotic remodeling in aged male mice with sarcopenia}},
author = {Yu Liu and Yuxin Zou and Honglin Chen and Qi Shang and Kun Chen and Feng Lin and Peng Zhang and You Zhang and Weicheng Qin and Huiwen Liu and Weiyu Qiu and Siyun Chen and Yuzhuo Zhang and Xingda Chen and Yan Gong and Yixuan Jiang and Jiahui He and Wenhua Zhao and Gengyang Shen and Xiaobing Jiang and Hui Ren},
journal = {Journal of Ginseng Research},
year = {2026},
month = jul,
doi = {10.1016/j.jgr.2026.101115},
url = {https://doi.org/10.1016/j.jgr.2026.101115},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Ginsenoside Rg2 attenuates TGF-β1/Smad-mediated fibrotic remodeling in aged male mice with sarcopenia
AU - Yu Liu
AU - Yuxin Zou
AU - Honglin Chen
AU - Qi Shang
AU - Kun Chen
AU - Feng Lin
AU - Peng Zhang
AU - You Zhang
AU - Weicheng Qin
AU - Huiwen Liu
AU - Weiyu Qiu
AU - Siyun Chen
AU - Yuzhuo Zhang
AU - Xingda Chen
AU - Yan Gong
AU - Yixuan Jiang
AU - Jiahui He
AU - Wenhua Zhao
AU - Gengyang Shen
AU - Xiaobing Jiang
AU - Hui Ren
PY - 2026
DA - 2026/07/14
JO - Journal of Ginseng Research
DO - 10.1016/j.jgr.2026.101115
UR - https://doi.org/10.1016/j.jgr.2026.101115
AB - Background: Sarcopenia is an age-related degenerative disease often accompanied by chronic low-grade inflammation and fibrotic remodeling, yet its specific underlying mechanisms remain unclear. This study aimed to explore the potential mechanism by which ginsenoside Rg2 ameliorates aging-related sarcopenia, with particular attention to TGF-β1/Smad-mediated fibrosis. Methods: Using single-cell sequencing, transcriptomic analysis, and Mendelian randomization (MR), we identified a causal relationship between transforming growth factor-β1 (TGF-β1)-mediated fibrosis and the progression of sarcopenia. We employed siRNA-mediated gene knockdown, real-time quantitative polymerase chain reaction (RT-qPCR), grip strength testing, western blotting, histological staining, molecular docking, molecular dynamics simulation, surface plasmon resonance (SPR), cellular thermal shift assay (CETSA), and drug affinity responsive target stability (DARTS) assays to evaluate the effects and potential mechanisms of Rg2 in aged male mice and C2C12 cell models. Results: Single-cell sequencing and MR analyses revealed that aging was associated with depletion of muscle satellite cells and skeletal muscle cells, together with increased neutrophils and fibroblasts. TGF-β1-related signaling showed a genetically supported association with sarcopenia-related traits and was closely associated with fibrotic remodeling in aged skeletal muscle. Rg2 treatment significantly mitigated age-associated weight gain while improving muscle mass, strength, and exercise endurance. Mechanistically, Rg2 interacted with TGF-β1 and attenuated downstream Smad2/3 phosphorylation in vitro and in vivo, thereby modulating inflammatory and fibrosis-related markers and partially reversing muscle tissue and cellular senescence. Conclusion: Our findings suggest that ginsenoside Rg2 alleviates TGF-β1/Smad-mediated fibrotic remodeling and improves the aging-related inflammatory-fibrotic microenvironment during skeletal muscle aging.
SN - 1226-8453
SN - 2093-4947
ER -