Effect of scutellarin on BV-2 microglial-mediated apoptosis in PC12 cells via JAK2/STAT3 signalling pathway

Sci Rep. 2024 Jun 11;14(1):13430. doi: 10.1038/s41598-024-64226-x.

Abstract

Previous studies have shown that scutellarin inhibits the excessive activation of microglia, reduces neuronal apoptosis, and exerts neuroprotective effects. However, whether scutellarin regulates activated microglia-mediated neuronal apoptosis and its mechanisms remains unclear. This study aimed to investigate whether scutellarin can attenuate PC12 cell apoptosis induced by activated microglia via the JAK2/STAT3 signalling pathway. Microglia were cultured in oxygen-glucose deprivation (OGD) medium, which acted as a conditioning medium (CM) to activate PC12 cells, to investigate the expression of apoptosis and JAK2/STAT3 signalling-related proteins. We observed that PC12 cells apoptosis in CM was significantly increased, the expression and fluorescence intensity of the pro-apoptotic protein Bax and apoptosis-related protein cleaved caspase-3 were increased, and expression of the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) was decreased. Phosphorylation levels and fluorescence intensity of the JAK2/STAT3 signalling pathway-related proteins JAK2 and STAT3 decreased. After treatment with scutellarin, PC12 cells apoptosis as well as cleaved caspase-3 and Bax protein expression and fluorescence intensity decreased. The expression and fluorescence intensity of Bcl-2, phosphorylated JAK2, and STAT3 increased. AG490, a specific inhibitor of the JAK2/STAT3 signalling pathway, was used. Our findings suggest that AG490 attenuates the effects of scutellarin. Our study revealed that scutellarin inhibited OGD-activated microglia-mediated PC12 cells apoptosis which was regulated via the JAK2/STAT3 signalling pathway.

Keywords: Apoptosis; JAK2/STAT3 signalling pathway; Microglia; Neurons; Scutellarin.

MeSH terms

  • Animals
  • Apigenin* / pharmacology
  • Apoptosis* / drug effects
  • Caspase 3 / metabolism
  • Glucose / metabolism
  • Glucuronates* / pharmacology
  • Janus Kinase 2* / metabolism
  • Mice
  • Microglia* / drug effects
  • Microglia* / metabolism
  • Neuroprotective Agents / pharmacology
  • PC12 Cells
  • Phosphorylation / drug effects
  • Rats
  • STAT3 Transcription Factor* / metabolism
  • Signal Transduction* / drug effects
  • Tyrphostins / pharmacology
  • bcl-2-Associated X Protein / metabolism

Substances

  • Apigenin
  • scutellarin
  • STAT3 Transcription Factor
  • Janus Kinase 2
  • Glucuronates
  • Jak2 protein, rat
  • Caspase 3
  • alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide
  • Glucose
  • Neuroprotective Agents
  • bcl-2-Associated X Protein
  • Stat3 protein, rat
  • Tyrphostins