title: Wogonin protects human retinal pigment epithelium cells from LPS-induced barrier dysfunction and inflammatory responses by regulating the TLR4/NF-κB signaling pathway.
abstract: Inflammation in the retinal pigment epithelium is an important contributor to the pathogenesis of age-related macular degeneration. Wogonin is a flavonoid isolated from the root of Scutellaria baicalensis and has multiple pharmacological effects, including anti‑inflammatory effects. The present study sought to determine if the pharmacological effects of wogonin were relevant to the treatment of AMD. ARPE‑19 cells were pre‑conditioned with different concentrations of wogonin (0‑50 µM) prior to induction of inflammation with LPS (2 µg/ml). Transepithelial electrical resistance analysis demonstrated that 24 h treatment with 10 and 50 µM wogonin ameliorated LPS‑induced changes. Reverse transcription-quantitative polymerase chain reaction (RT‑qPCR) and immunoﬂuorescence analyses revealed that wogonin restrained LPS-induced tight junction proteins, claudin‑1 and ZO‑1. LPS‑induced upregulation of inflammatory mediators in ARPE‑19 cells, including IL‑1β, IL‑6, IL‑8, cyclooxygenase‑2 (COX‑2), inducible nitric oxide synthase (iNOS) and TNF‑α was reduced after pre-treatment with wogonin. In addition, RT‑qPCR and western blotting demonstrated that wogonin inhibited the expression of TLR4 in LPS‑stimulated ARPE‑19 cells. This is a novel mechanism indicating that pre‑treatment with wogonin could attenuate the TLR4/NF‑κB‑mediated inflammatory response in LPS‑stimulated ARPE‑19 cells, and thus could be a potential therapy for the treatment of AMD.
authors.affiliation: Eye Institute, Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu 213003, P.R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Otorhinolaryngology Head & Neck Surgery, Hospital of Jiangnan University, Wuxi, Jiangsu 214062, P.R. China.
authors.forename: Danni
authors.initials: D
authors.lastname: Guo
authors.affiliation: Eye Institute, Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu 213003, P.R. China.
authors.forename: Guohua
authors.initials: G
authors.lastname: Lu
mesh_terms: D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology; D044950:Flavanones / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D008070:Lipopolysaccharides / Q000276:immunology*; D016328:NF-kappa B / Q000276:immunology*; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D031363:Scutellaria / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000276:immunology*
chemical_list: D000893:Anti-Inflammatory Agents; D004365:Drugs, Chinese Herbal; D044950:Flavanones; D008070:Lipopolysaccharides; D016328:NF-kappa B; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; C085514:wogonin