PloS one
Dioscin attenuates D‑galactose‑induced retinal pigment epithelium senescence and epithelial-mesenchymal transition via the TGF‑β2/PI3K/Akt/β‑catenin pathway
By Ouyang Q, Zhou H, Ji C and 5 others.
Abstract
Purpose
This study aimed to evaluate the protective effects of Dioscin in an age-related macular degeneration (AMD) -like model and to explore its potential therapeutic mechanisms.
Methods
The therapeutic potential of Dioscin for AMD was investigated using D-galactose-induced senescence models in ARPE-19 cells (an in vitro preliminary screening model) and C57BL/6J mice using RT-qPCR, western blotting, immunofluorescence, and SA-β-gal staining. Bioinformatic analysis and molecular docking identified TGF-β2 as a computationally predicted potential target of Dioscin in AMD. Key mechanisms involving TGF-β2 and the PI3K/Akt/β-catenin signaling pathway were assessed in vitro using RT-qPCR, western blotting.
Results
In D-galactose-induced senescence models, Dioscin significantly alleviated RPE senescence and EMT. Single-cell transcriptome analysis revealed that TGF-β2 is highly expressed in choroidal vascular endothelial cells of AMD patients. Mechanistically, computational predictions (molecular docking and dynamics simulations) identified TGF-β2 as a computationally predicted potential target of Dioscin, and experimental data showed that Dioscin suppressed D-galactose-induced activation of the TGF-β2/PI3K/Akt/β-catenin pathway in RPE cells, suggesting a potential paracrine regulatory mechanism.