Fig. 8.

AR/Gα/PLC/IP3/CaMKK is involved in the activation of AMPK/GSK-3β/Nrf2 pathway in vivo. a The effects of Apelin 13 on the expression of CaMKK and IP3 in the brain. b In ARKO rats, the AMPK/GSK-3β/Nrf2 pathway was inhibited and the expression levels of PLC, IP3, CaMKK, and Nrf2 were also decreased. The levels of SOD (c), ROS (d), infarct volume ratio (e), caspase 3 (f) IL-1β (g), and TNF-α (h) were measured as before. The columns and error bars were represented as means ± SD. ^##P < 0.01 vs. the sham group; **P < 0.01 vs. the I/R treatment group. ^&&P < 0.05 vs. the WT rats. i Potential mechanism underlying the neuro-protective effects of Apelin 13 on I/R-induced brain injuries in rats and PC12 cells. Apelin 13 protected the brain against ischemic stroke-induced oxidative stress and inflammation through AMPK-mediated inhibitory phosphorylation of GSK-3β downstream of AR/G-coupled receptors pathway, and further induced Nrf2-mediated antioxidant proteins expressions