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Salvianolic Acid A Protects Retinal Pigment Epithelium From OX-LDL-induced Inflammation in an Age-Related Macular Degeneration Model

Ke Mao, Wanting Shu, Qinghua Qiu, Qing Gu, Xingwei Wu

Discov Med. 2017 Feb;23(125):129-147.

PMID: 28371616

Abstract:

Background:
Salvianolic acid A (Sal A), an active monomer of Salvia miltiorrhiza, is a phenolic carboxylic acid derivative. The present study was performed to investigate the underlying mechanism of the anti-inflammation effect of Sal A, especially focusing on mTOR-KEAP1-Nrf2 and P2X7R-PKR-NLRP3 signaling pathways.
Methods:
SD mice were divided into four groups: PBS, oxidized-low density lipoprotein (ox-LDL, 3 mg/kg), and ox-LDL (3 mg/kg) + Sal A (5 mg/kg) and + Sal A (10 mg/ml) groups. In in vitro experiments, ARPE-19 cells were cultured with serum free medium (SFM) or ox-LDL (100 mg/L), with or without Sal A (5 µM/50 µM) for 24 hours.
Results:
Sal A attenuated ox-LDL-induced lipidosis and apoptosis in the retinal pigment epithelium (RPE) layer. Ox-LDL elevated ROS level and induced RPE inflammation, which were inhibited by Sal A pretreatment. Sal A activated PI3K/AKT/mTOR signaling pathway, which further promoted the disassociation of Keap1-Nrf2 complex and the phosphorylation of Nrf2. PI3K and mTOR chemical inhibitors abolished Sal A-induced Nrf2 activation while it had no influence on nlrp3 expression. Sal A also inhibited RPE inflammation by inactivating the P2x7r-Pkr-Nlrp3 signaling pathway.
Conclusions:
The above results indicate that Sal A protects RPE from lipid oxidative damage and chronic inflammation through up-regulating Nrf2 and inactivating the P2x7r-Pkr-Nlrp3 signaling pathway.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP96574015 Salvianolic acid A Salvianolic acid A 96574-01-5 Price
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