4-(Phenylsulfanyl) Butan-2-One Attenuates the Inflammatory Response Induced by Amyloid-β Oligomers in Retinal Pigment Epithelium Cells

Mar Drugs. 2020 Dec 23;19(1):1. doi: 10.3390/md19010001.

Abstract

Age-related macular degeneration (AMD) is a progressive eye disease that causes irreversible impairment of central vision, and effective treatment is not yet available. Extracellular accumulation of amyloid-beta (Aβ) in drusen that lie under the retinal pigment epithelium (RPE) has been reported as one of the early signs of AMD and was found in more than 60% of Alzheimer's disease (AD) patients. Extracellular deposition of Aβ can induce the expression of inflammatory cytokines such as IL-1β, TNF-α, COX-2, and iNOS in RPE cells. Thus, finding a compound that can effectively reduce the inflammatory response may help the treatment of AMD. In this research, we investigated the anti-inflammatory effect of the coral-derived compound 4-(phenylsulfanyl) butan-2-one (4-PSB-2) on Aβ1-42 oligomer (oAβ1-42) added to the human adult retinal pigment epithelial cell line (ARPE-19). Our results demonstrated that 4-PSB-2 can decrease the elevated expressions of TNF-α, COX-2, and iNOS via NF-κB signaling in ARPE-19 cells treated with oAβ1-42 without causing any cytotoxicity or notable side effects. This study suggests that 4-PSB-2 is a promising drug candidate for attenuation of AMD.

Keywords: 4-(Phenylsulfanyl) Butan-2-One; amyloid-β; coral; inflammatory responses; retinal pigment epithelium cells.

MeSH terms

  • Amyloid beta-Peptides / toxicity*
  • Anti-Inflammatory Agents / pharmacology*
  • Butanones / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Cyclooxygenase 2 / metabolism
  • Humans
  • Inflammation Mediators / metabolism*
  • Interleukin-1beta / metabolism
  • Macular Degeneration / drug therapy*
  • Macular Degeneration / metabolism
  • Macular Degeneration / pathology
  • NF-kappa B / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Peptide Fragments / toxicity*
  • Retinal Pigment Epithelium / drug effects*
  • Retinal Pigment Epithelium / metabolism
  • Retinal Pigment Epithelium / pathology
  • Sulfides / pharmacology*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • 4-(phenylsulfanyl)butan-2-one
  • Amyloid beta-Peptides
  • Anti-Inflammatory Agents
  • Butanones
  • IL1B protein, human
  • Inflammation Mediators
  • Interleukin-1beta
  • NF-kappa B
  • Peptide Fragments
  • Sulfides
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • amyloid beta-protein (1-42)
  • NOS2 protein, human
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • PTGS2 protein, human