title: Sinomenine inhibits microglial activation by Aβ and confers neuroprotection.
abstract: BACKGROUND
  Neuroinflammation is an important contributor to the development of neurodegenerative diseases, including Alzheimer's disease. Thus, there is a keen interest in identifying compounds, especially from herbal sources, that can inhibit neuroinflammation. Amyloid-β (Aβ) is a major component of the amyloid plaques present in the brains of Alzheimer's disease patients. Here, we examined whether sinomenine, present in a Chinese medicinal plant, prevents oligomeric Aβ-induced microglial activation and confers protection against neurotoxicity.
  
  
  METHODS
  Oligomeric amyloid-β was prepared from Aβ(1-42). Intracellular reactive oxygen species production was determined using the dye 2',7'-dichlorodihydrofluorescin diacetate. Nitric oxide level was assessed using the Griess reagent. Flow cytometry was used to examine the levels of inflammatory molecules. BV2-conditioned medium was used to treat hippocampal cell line (HT22) and primary hippocampal cells in indirect toxicity experiments. Toxicity was assessed using MTT reduction and TUNEL assays.
  
  
  RESULTS
  We found that sinomenine prevents the oligomeric Aβ-induced increase in levels of reactive oxygen species and nitric oxide in BV2 microglial cells. In addition, sinomenine reduces levels of Aβ-induced inflammatory molecules. Furthermore, sinomenine protects hippocampal HT22 cells as well as primary hippocampal cells from indirect toxicity mediated by Aβ-treated microglial cells, but has no effect on Aβ-induced direct toxicity to HT22 cells. Finally, we found that conditioned medium from Aβ-treated BV2 cells contains increased levels of nitric oxide and inflammatory molecules, but the levels of these molecules are reduced by sinomenine.
  
  
  CONCLUSIONS
  Sinomenine prevents oligomeric Aβ-induced microglial activation, and confers protection against indirect neurotoxicity to hippocampal cells. These results raise the possibility that sinomenine may have therapeutic potential for the treatment of Alzheimer's diseases as well as other diseases that involve neuroinflammation.
authors.affiliation: National Brain Research Centre, Manesar, Haryana-122050, India. sharmas@nbrc.ac.in
authors.forename: Shilpa Mishra
authors.initials: SM
authors.lastname: Shukla
authors.forename: Shiv K
authors.initials: SK
authors.lastname: Sharma
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000737:chemistry; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D006801:Humans; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D009019:Morphinans / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D017077:Culture Media, Conditioned; D009019:Morphinans; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C075222:amyloid beta-protein (1-42); D009569:Nitric Oxide; C009271:sinomenine