Oleanolic Acid Inhibiting the Differentiation of Neural Stem Cells into Astrocyte by Down-Regulating JAK/STAT Signaling Pathway

Am J Chin Med. 2016;44(1):103-17. doi: 10.1142/S0192415X16500075.

Abstract

To investigate the effect of oleanolic acid (OA) on the differentiation of neural stem cells (NSCs) induced by A[Formula: see text] via regulating the JAK/STAT signaling pathway, a neurotoxicity cell model involving the induction of NSCs by soluble A[Formula: see text] (5 [Formula: see text]M) was used. The WST-1 method and immunofluorescence tests were used respectively to detect the activity of cell model and the expression of GFAP[Formula: see text]/DAPI and Tubulin[Formula: see text]/DAPI. Western blotting and real-time PCR analyses were used to observe the effects of OA on NSCs differentiation by examining key targets of the JAK/STAT signal transduction pathway. Compared with normal NSCs, A[Formula: see text]-induced NSCs had down-regulated expression of Ngn1 and up-regulated STAT3 expression and phosphorylation, and inhibited neuronal differentiation. OA treatment effectively inhibited the A[Formula: see text]-induced activation of JAK/STAT signaling, with a significant increase in Ngn1 expression and a significant decrease in p-STAT3/STAT3. These results indicate that OA could inhibit the excessive differentiation of NSCs into astrocytes by down-regulating JAK/STAT signaling which might retard the progress of AD.

Keywords: A; JAK/STAT Signaling Pathway; NSCs Differentiation; Neural Stem Cells; Oleanolic Acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / pharmacology
  • Animals
  • Astrocytes*
  • Cell Differentiation / drug effects*
  • Cell Differentiation / genetics*
  • Cells, Cultured
  • Depression, Chemical
  • Down-Regulation / drug effects*
  • Female
  • Janus Kinases*
  • Mice, Inbred Strains
  • Neural Stem Cells / cytology*
  • Oleanolic Acid / pharmacology*
  • Peptide Fragments / pharmacology
  • Pregnancy
  • STAT3 Transcription Factor*
  • Signal Transduction / drug effects*
  • Signal Transduction / genetics*

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • STAT3 Transcription Factor
  • amyloid beta-protein (25-35)
  • Oleanolic Acid
  • Janus Kinases