Metformin, the first medication that is often prescribed for the treatment of Type-2 Diabetes Mellitus (T2DM), was recently found to be neuroprotective. To study the mechanism underlying the neuroprotective effect of metformin, we pre-treated primary spinal cord neurons with 50 µM or 100 µM µM metformin for 2 hours prior to treatment with hydrogen peroxide (H2O2) for up to 48 hours. Our results showed that H2O2 increased the expression of purinergic receptor P2X7 (P2X7R) in spinal cord neurons, which promoted the downstream pro-inflammatory cytokines release and oxidative stress. We found that metformin could reverse these pro-inflammatory and pro-oxidative effects of H2O2. Besides, P2X7R knockdown by siRNA suppressed H2O2-induced proinflammatory cytokine release and oxidative stress response. In conclusion, our results show that metformin can alleviate H2O2-induced inflammation and oxidative stress via modulating the P2X7R signaling pathway.
Inhibition of cPLA2 activation by Ginkgo biloba extract protects spinal cord neurons from glutamate excitotoxicity and oxidative stress-induced cell death