Neuronal Apoptosis Preventive Potential of Sophocarpine via Suppression of Aβ-Accumulation and Down-Regulation of Inflammatory Response

Dokl Biochem Biophys. 2021 Mar;497(1):116-122. doi: 10.1134/S1607672921020186. Epub 2021 Apr 24.

Abstract

In the current study sophocarpine was investigated in vitro for prevention of β-amyloid induced PC12 neuronal cell damage. Exposure to β-amyloid caused a dose-dependent suppression in growth of PC12 cells with maximum reduction at 10 μM. Sophocarpine pre-treatment reversed suppressive effect of β-amyloid (10 μM) on PC12 cell growth in concentration-based manner. In sophocarpine pre-treated PC12 cells the β-amyloid mediated PGE2 level elevation was attenuated significantly at 0.25-2 μM doses. Moreover, in sophocarpine pretreated PC12 cells the β-amyloid mediated promotion of COX-2 level was also inhibited. Sophocarpine pre-treatment attenuated iNOS expression in β-amyloid exposed PC12 cells at 0.25-2 μM doses. Pre-treatment of PC12 cells with sophocarpine suppressed NO-species generation induced by β-amyloid exposure. In sophocarpine pretreated PC12 cells elevation of nuclear NF-κB expression induced by β-amyloid was significantly inhibited. In summary, sophocarpine prevents reduction of PC12 cell growth induced by β-amyloid exposure via inhibition of inflammatory processes. The preventive effect of sophocarpine on β-amyloid induced PC12 cell damage is associated with inhibition of NF-κB nuclear translocation. Therefore, sophocarpine may be used for treatment of neurological disorders like Alzheimer's disease.

Keywords: Alzheimer’s disease; anti-inflammatory; natural product; sophocarpine; β-amyloid.

MeSH terms

  • Alkaloids / pharmacology*
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Apoptosis / drug effects*
  • Cyclooxygenase 2 / metabolism
  • Inflammation / metabolism
  • Inflammation / pathology
  • NF-kappa B / metabolism
  • Neurons / cytology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurons / pathology
  • Neuroprotective Agents / pharmacology*
  • PC12 Cells
  • Rats
  • Signal Transduction / drug effects

Substances

  • Alkaloids
  • Amyloid beta-Peptides
  • NF-kappa B
  • Neuroprotective Agents
  • sophocarpine
  • Cyclooxygenase 2