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

To investigate the effect of oleanolic acid (OA) on the differentiation of neural stem cells (NSCs) induced by Aβ25-35 via regulating the JAK/STAT signaling pathway, a neurotoxicity cell model involving the induction of NSCs by soluble Aβ25-35 (5 μM) was used. The WST-1 method and immunofluorescence tests were used respectively to detect the activity of cell model and the expression of GFAP+/DAPI and Tubulin+/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, Aβ25-35-induced NSCs had down-regulated expression of Ngn1 and up-regulated STAT3 expression and phosphorylation, and inhibited neuronal differentiation. OA treatment effectively inhibited the Aβ25-35-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.