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.