3,4-oxo-isopropylidene-shikimic acid inhibits cerebral ischemia-induced oxidative stress and neuronal apoptosis in rats

Background: To investigate the potential protective effects of 3,4-oxo-isopropylidene-shikimic acid (ISA) on brain ischemic injury in rats. Methods: Cell Counting Kit-8, flow cytometry, and TUNEL were used to evaluate the cell viability and the apoptosis rate in vitro and in situ. Reactive oxygen species generation was determined by DCFH-DA assay. qPCR and Western blot were used to test the molecular mechanisms related to the anti-apoptosis effects. Result: Protective effect of pre-conditioning of ISA on the brain injury caused by ischemia was observed. ISA treatment showed anti-apoptosis effects on isolated primary astrocytes and neurons. ROS generation was also significantly scavenged by treatment of ISA. The treatment with ISA protected astrocytes from hypoxic condition-induced apoptosis and ischemic injury. The underlying mechanisms revealed by qPCR and WB showed that the level of mRNA and protein expression of Bax, Bcl-2, and caspase-3 were significantly down-regulated by ISA treatment (P < 0.05). Pre-conditioning with ISA is beneficial in reducing the neuronal damage caused by brain ischemia. Conclusion: Treatment with ISA reduces apoptosis and ROS over-generation caused by ischemic injury. Pre-conditioning with ISA resulted in significantly protective effects on brain under ischemic condition.