Full
Outline
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).
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.
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.
Ginsenoside Rk3 alleviates RPE cell senescence and reduces retinal CNV area in nAMD mice by enhancing autophagy through inhibition of mTOR.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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