Inhibitory Effect of 1,3-Dipalmitoyl-2-Oleoylglycerol Derived from Rice Bran oil on Ischemia-Induced Neurotoxicity
Background : Ischemic stroke is a common cause of adult disability and death worldwide. Excessive oxidative stress is an important pathogenic mechanism in ischemic stroke. Major reduction of endogenous antioxidative systems increases production of free radicals inducing peroxidation of lipid, protein, and nucleic acid. 1,3-Dipalmitoyl-2-oleoylglycerol (DPOG) is a triglyceride found in oils from various natural sources such as palm kernels, sunflower seeds and rice bran. We found DPOG as an active constituent of rice bran oil. In the present study, we investigated neuroprotective effect of DPOG derived from rice bran oil on excitotoxicity in cultured neurons and on ischemic brain injury in rats. Methods and Results : Transient focal ischemic brain damage was induced by 2 h middle cerebral artery occlusion followed by 24h reperfusion (MCAO/reperfusion) in rats. After MCAO/reperfusion, the infarct and edema volume of brain tissue was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining methods. Glutathione concentration and lipid peroxidation rate were measured in brain tissue. The expression levels of phosphorylated mitogen activated proteins kinases (MAPKs), inflammatory factors, and anti-apoptotic and pro-apoptotic proteins in brain tissue were detected by Western blot. Cerebral cortical neuronal cells were cultured in 15-days-old fetus. Cortical neurons were incubated with 1 mM N-methyl-D-aspartate (NMDA) for 14 h to produce excitotoxicity. Cell viability was measured by MTT assay. DPOG (1-5 mg/kg) significantly reduced MCAO/reperfusion-induced infarction and edema formation, neurological deficits, and brain cell death. Depletion of glutathione level and lipid peroxidation induced by MCAO/reperfusion were inhibited by administration of DPOG. The increase of phosphorylated MAPKs, inflammatory factors, and proapoptotic proteins and the decrease of antiapoptotic protein in ischemic brain were significantly inhibited by treatment with DPOG. DPOG (0.1-10 uM) inhibited 1 mM NMDA-induced neuronal cell death in cultured cortical neurons. Conclusion : From the above results, the present study provides an evidence that DPOG derived from rice bran oil might be effectively applied for the treatment of ischemic stroke.