ReferenceID 600

Salvianolic acid A protects RPE cells against oxidative stress through activation of Nrf2/HO-1 signaling

Free Radic Biol Med

Reactive oxygen species (ROS) impair the physiological functions of retinal pigment epithelial (RPE) cells, which is known as one major cause of age-related macular degeneration. Salvianolic acid A (Sal A) is the main e

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Reference Id
600
Evidence Id
17190
Core Evidence Id
17190
Source Reference Id
1185
Herb2 Reference Id
HBREF001981
Subject Paper Key
HBIN042900_24486344
Pubmed Id
24486344
Doi
10.1016/j.freeradbiomed.2014.01.025
Paper Title
Salvianolic acid A protects RPE cells against oxidative stress through activation of Nrf2/HO-1 signaling
Paper Abstract
Reactive oxygen species (ROS) impair the physiological functions of retinal pigment epithelial (RPE) cells, which is known as one major cause of age-related macular degeneration. Salvianolic acid A (Sal A) is the main effective aqueous extract of Salvia miltiorrhiza. The aim of this study was to test the potential role of Sal A against oxidative stress in cultured RPE cells and to investigate the underlying mechanistic signaling pathways. We observed that Sal A significantly inhibited hydrogen peroxide (H2O2)-induced primary and transformed RPE cell death and apoptosis. H2O2-stimulated mitogen-activated protein kinase activation, ROS production, and subsequent proapoptotic AMP-activated protein kinase activation were largely inhibited by Sal A. Further, Sal A stimulation resulted in a fast and dramatic activation of Akt/mammalian target of rapamycin complex 1 (mTORC1) signaling, followed by phosphorylation, accumulation, and nuclear translocation of the NF-E2-related factor 2 (Nrf2), along with increased expression of the antioxidant-response element-dependent gene heme oxygenase-1 (HO-1). Both Nrf2 and HO-1 were required for Sal A-mediated cytoprotective effect, as Nrf2/HO-1 inhibition abolished Sal A-induced beneficial effects against H2O2. Meanwhile, the PI3K/Akt/mTORC1 chemical inhibitors not only suppressed Sal A-induced Nrf2/HO-1 activation, but also eliminated its cytoprotective effect in RPE cells. These observations suggest that Sal A activates the Nrf2/HO-1 axis in RPE cells and protects against oxidative stress via activation of Akt/mTORC1 signaling.
Journal
Free Radic Biol Med
Publish Year
2014
Experiment Subject
rpe cells
Experiment Type
Cell Experiment
Phenotype Related
Paper Title Cn
Paper Title En
Salvianolic acid A protects RPE cells against oxidative stress through activation of Nrf2/HO-1 signaling
Bilingual Status
semi_complete