PROTECTION BY BORNEOL ON CORTICAL NEURONS AGAINST OXYGEN-GLUCOSE DEPRIVATION/REPERFUSION: INVOLVEMENT OF ANTI-OXIDATION AND ANTI-INFLAMMATION THROUGH NUCLEAR TRANSCRIPTION FACTOR κB SIGNALING PATHWAY

Borneol, a terpene and bicyclic organic compound found in several species, can easily penetrate the blood-brain barrier (BBB) and helps the absorption of many agents through BBB in the brain, but there has been no study about its direct action on neurons in the CNS. In the present study, we used an in vitro ischemic model of oxygen-glucose deprivation followed by reperfusion (OGD/R) to investigate the neuroprotective effects of borneol and the related mechanisms. We demonstrated that borneol reversed OGD/R-induced neuronal injury, nuclear condensation, intracellular reactive oxygen species (ROS) generation, and mitochondrial membrane potential dissipation. The elevation of nitric oxide (NO), the increase of inducible nitric oxide synthase (iNOS) enzymatic activity and the upregulation of iNOS expression were also attenuated by borneol. The inhibition of caspase-related apoptotic signaling pathway was consistently involved in the neuroprotection afforded by borneol. Meanwhile, borneol inhibited proinflammatory factor release and I kappa B alpha degradation, and blocked nuclear transcription factor kappa appaB (NF-kappa B) p65 nuclear translocation induced by OGD/R. On the other hand, borneol did not show obvious effect on the inhibition of phospho-IKK alpha activation. Furthermore, it failed to affect the OGD/R-induced enhanced level of phospho-SAPK/JNK. In conclusion, our study indicated that borneol protects against cerebral ischemia/reperfusion injury through multifunctional cytoprotective pathways. The mechanisms of this reversal from OGD/R may be involved in the alleviation of intracellular ROS and iNOS/NO pathway, inhibition of inflammatory factor release and depression of caspase-related apoptosis. Among these effects, the inhibi-tion of I kappa B alpha-NF-kappa B and translocation signaling pathway might play a significant role in the neuroprotection of borneol. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.