Ginsenoside Rk3 alleviates retinal pigment epithelial cell senescence by enhancing autophagy <italic style="font-style: italic">via</italic> mTOR inhibition

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Ginsenoside Rk3 alleviates retinal pigment epithelial cell senescence by enhancing autophagy via mTOR inhibition

Basic Medicine | 更新时间：2025-10-13

- Ginsenoside Rk3 alleviates retinal pigment epithelial cell senescence by enhancing autophagy via mTOR inhibition
- Journal of Army Medical University Vol. 47, Issue 19, Pages: 2340-2350(2025)
- 作者机构：
  
  1.陆军特色医学中心（第三军医大学大坪医院）眼科重庆
  2.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
  3.重庆理工大学药学与生物工程学院重庆
- 作者简介：
- 基金信息：
  
  the General Project of Natural Science Foundation of Chongqing(CSTB2024NSCQ-KJFZZDX0038)
- DOI：10.16016/j.2097-0927.202507053
  CLC： R285.5;R322.91;R329.25
- Received：17 July 2025，
  
  Revised：2025-09-10，
  
  Accepted：10 September 2025，
  
  Published：15 October 2025
- 稿件说明：
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赫飞翔，刘雪梅，唐倩，等.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［J］.陆军军医大学学报，2025，47（19）：2340-2350.DOI：10.16016/j.2097-0927.202507053.

HE F X，LIU X M，TANG Q，et al.Ginsenoside Rk3 alleviates retinal pigment epithelial cell senescence by enhancing autophagy via mTOR inhibition［J］.J Army Med Univ，2025，47（19）：2340-2350.DOI：10.16016/j.2097-0927.202507053.
赫飞翔，刘雪梅，唐倩，等.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［J］.陆军军医大学学报，2025，47（19）：2340-2350.DOI：10.16016/j.2097-0927.202507053. DOI：

HE F X，LIU X M，TANG Q，et al.Ginsenoside Rk3 alleviates retinal pigment epithelial cell senescence by enhancing autophagy via mTOR inhibition［J］.J Army Med Univ，2025，47（19）：2340-2350.DOI：10.16016/j.2097-0927.202507053. DOI：

摘要

目的

2

探索人参皂苷Rk3在减轻视网膜色素上皮（retinal pigment epithelial，RPE）细胞衰老及治疗新生血管性老年性黄斑变性（neovascular age-related macular degeneration，nAMD）的作用及机制。

方法

2

通过过氧化氢诱导ARPE-19细胞衰老模型和nAMD小鼠模型，验证人参皂苷Rk3减轻RPE细胞衰老和缩小脉络膜新生血管（choroidal neovascularization，CNV）面积的药物活性；通过转录组测序分析差异基因表达谱变化；通过蛋白免疫印迹实验检测mTOR、S6K1、p-S6K1、4EBP1、p-4EBP1、p62、LC3A/B等蛋白的表达水平；通过分子对接和动力学模拟分析人参皂苷Rk3与mTOR蛋白的亲和力。

结果

2

①细胞实验发现人参皂苷Rk3显著减轻ARPE-19细胞衰老（

P

<

0.05）；②动物实验证实人参皂苷Rk3显著缩小nAMD小鼠视网膜CNV面积（

P

<

0.01），且与临床一线治疗药物阿柏西普效果相当（

P

>

0.05）。③转录组测序提示人参皂苷Rk3导致PI3K-Akt信号通路富集，蛋白免疫印迹实验显示人参皂苷Rk3 可抑制 mTORC1信号的过度激活（

P

<

0.05），同时增强细胞自噬（

P

<

0.05）。④分子对接和动力学模拟研究进一步验证人参皂苷Rk3很可能靶向mTOR蛋白减轻RPE细胞衰老。

结论

2

人参皂苷Rk3通过抑制mTOR增强细胞自噬，减轻了RPE细胞衰老并缩小了nAMD小鼠视网膜CNV面积。

Abstract

Objective

2

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

2

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

2

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

2

Ginsenoside Rk3 alleviates RPE cell senescence and reduces retinal CNV area in nAMD mice by enhancing autophagy through inhibition of mTOR.

关键词

Keywords

references

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