Daucosterol protects neurons against oxygen–glucose deprivation/reperfusion-mediated injury by activating IGF1 signaling pathway

• Post-treatment of daucosterol protects neurons against OGD/R-mediated injury.
• Daucosterol reduces neuronal loss and apoptotic rate.
• Daucosterol enhances the expression of IGF1 protein in OGD/R-treated neurons.
• Daucosterol reverses the down-regulation of Mcl-1 and Bcl-2 in OGD/R-treated neurons.
• Daucosterol raises the ratio of Bcl-2/Bax in OGD/R-treated neurons.

We previously reported that daucosterol (a sterolin) up-regulates the expression of insulin-like growth factor I (IGF1)1 protein in neural stem cells. In this study, we investigated the effects of daucosterol on the survival of cultured cortical neurons after neurons were subjected to oxygen and glucose deprivation and simulated reperfusion (OGD/R)2, and determined the corresponding molecular mechanism. The results showed that post-treatment of daucosterol significantly reduced neuronal loss, as well as apoptotic rate and caspase-3 activity, displaying the neuroprotective activity. We also found that daucosterol increased the expression level of IGF1 protein, diminished the down-regulation of p-AKT3 and p-GSK-3β4, thus activating the AKT5 signal pathway. Additionally, it diminished the down-regulation of the anti-apoptotic proteins Mcl-16 and Bcl-27, and decreased the expression level of the pro-apoptotic protein Bax8, thus raising the ratio of Bcl-2/Bax. The neuroprotective effect of daucosterol was inhibited in the presence of picropodophyllin (PPP)9, the inhibitor of insulin-like growth factor I receptors (IGF1R)10. Our study provided information about daucosterol as an efficient and inexpensive neuroprotectants, to which the IGF1-like activity of daucosterol contributes. Daucosterol could be potentially developed as a medicine for ischemic stroke treatment.