NEUROPROTECTIVE ACTIVITY OF (1S,2E,4R,6R,-7E,11E)-2,7,11-CEMBRATRIENE-4,6-DIOL (4R) IN VITRO AND IN VIVO IN RODENT MODELS OF BRAIN ISCHEMIA

(1S,2E,4R,6R,-7E,11E)-2,7,11-cembratriene-4,6-diol (4R) is a precursor to key flavor ingredients in leaves of Nicotiana species. The present study shows 4R decreased brain damage in rodent ischemic stroke models. The 4R-pre-treated mice had lower infarct volumes (26.2 +/- 9.7 mm(3)) than those in control groups (untreated: 63.4 +/- 4.2 mm(3), DMSO: 60.2 +/- 14.2 mm(3)). The 4R-posttreated rats also had less infarct volumes (120 +/- 65 mm(3)) than those in the rats of the DMSO group (291 +/- 95 mm(3)). The results from in vitro experiments indicate that 4R decreased neuro2a cell (neuroblastoma cells) apoptosis induced by oxygen-glucose deprivation (OGD), and improved the population spikes' (PSs) recovery in rat acute hippocampal slices under OGD; a phosphatidylinositol 3-kinase (PI3K) inhibitor, wortmannin, abolished the effect of 4R on PSs recovery. Furthermore, 4R also inhibited monocyte adhesion to murine brain-derived endothelial (bEND5) cells and upregulation of intercellular adhesion molecule-1(ICAM-1) induced by OGD/reoxygenation (OGD/R), and restored the p-Akt level to pre-OGD/R values in bEND5 cells. In conclusion, the present study indicates that 4R has a protective effect in rodent ischemic stroke models. Inhibition of ICAM-1 expression and restoration of Akt phosphorylation are the possible mechanisms involved in cellular protection by 4R. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.