Ginsenoside Rk3 alleviates retinal pigment epithelial cell senescence by enhancing autophagy via mTOR inhibition
10.16016/j.2097-0927.202507053
- VernacularTitle:人参皂苷Rk3通过抑制mTOR增强细胞自噬减轻视网膜色素上皮细胞衰老
- Author:
Feixiang HE
1
;
Xuemei LIU
;
Qian TANG
;
Ting LIU
Author Information
1. 陆军特色医学中心(第三军医大学大坪医院)眼科 重庆;中国人民解放军联勤保障部队第九〇四医院眼科 江苏无锡
- Keywords:
neovascular age-related macular degeneration;
ginsenoside Rk3;
retinal pigment epithelial cells;
cellular senescence;
autophagy
- From:
Journal of Army Medical University
2025;47(19):2340-2350
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role and mechanism of ginsenoside Rk3 in alleviating the senescence of retinal pigment epithelial(RPE)cells and in treating neovascular age-related macular degeneration(nAMD).Methods An ARPE-19 cell senescence model induced by hydrogen peroxide and an nAMD mouse model were subjected to validate the pharmacological activity of ginsenoside Rk3 in reducing RPE cell senescence and shrinking choroidal neovascularization(CNV)area.Transcriptome sequencing was performed to analyze the changes in differential gene expression profiles.Western blotting was used to detect the expression levels of mTOR,S6K1,p-S6K1,4EBP1,p-4EBP1,p62,and LC3A/B.Molecular docking and dynamics simulations were conducted to analyze the binding affinity of ginsenoside Rk3 with mTOR protein.Results ① Cell experiments showed that ginsenoside Rk3 significantly alleviated the senescence in ARPE-19 cells(P<0.05).② Animal experiments confirmed that ginsenoside Rk3 significantly reduced the retinal CNV area in nAMD mice(P<0.01),and its efficacy was comparable to the first-line clinical drug aflibercept(P>0.05).③ Transcriptome sequencing suggested that ginsenoside Rk3 led to enrichment of the PI3K-Akt signaling pathway.Western blotting showed that ginsenoside Rk3 inhibited the overactivation of mTORC1 signaling(P<0.05)and simultaneously enhanced cellular autophagy(P<0.05).④ Molecular docking and dynamics simulations further validated that ginsenoside Rk3 probably targets mTOR to alleviate RPE cell senescence.Conclusion Ginsenoside Rk3 alleviates RPE cell senescence and reduces retinal CNV area in nAMD mice by enhancing autophagy through inhibition of mTOR.
