title: Salvianolic acid A protects retinal pigment epithelium from OX-LDL-induced inflammation in an age-related macular degeneration model.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Mao
authors.affiliation: Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Wanting
authors.initials: W
authors.lastname: Shu
authors.affiliation: Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Qiu
authors.affiliation: Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Gu
authors.affiliation: Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xingwei
authors.initials: X
authors.lastname: Wu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002109:Caffeic Acids / Q000627:therapeutic use*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D020287:In Situ Nick-End Labeling; D007773:Lactates / Q000627:therapeutic use*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008268:Macular Degeneration / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000187:drug effects* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002109:Caffeic Acids; D007773:Lactates; D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein; C066201:salvianolic acid A; D051057:Proto-Oncogene Proteins c-akt