title: 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.
abstract: (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-pretreated mice had lower infarct volumes (26.2±9.7 mm3) than those in control groups (untreated: 63.4±4.2 mm3, DMSO: 60.2±14.2 mm3). The 4R-posttreated rats also had less infarct volumes (120±65 mm3) than those in the rats of the DMSO group (291±95 mm3). 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.
authors: Department of Biochemistry, Universidad Central del Caribe. Ave. Laurel #100, Santa Juanita, Bayamon, Puerto Rico, 00956.
authors: Antonio H
authors: AH
authors: Martins
authors: Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267.
authors: Jing
authors: J
authors: Hu
authors: Department of Neurobiology, Neuroscience Institute, Morehouse School of Medicine, Atlanta, Georgia 30310.
authors: Zhenfeng
authors: Z
authors: Xu
authors: Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267.
authors: Chaofeng
authors: C
authors: Mu
authors: Department of Biochemistry, Universidad Central del Caribe. Ave. Laurel #100, Santa Juanita, Bayamon, Puerto Rico, 00956.
authors: Paloma
authors: P
authors: Alvarez
authors: Department of Neurobiology, Neuroscience Institute, Morehouse School of Medicine, Atlanta, Georgia 30310.
authors: Byron D
authors: BD
authors: Ford
authors: Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe. 1800 Bienville Drive, Monroe, LA 71201.
authors: Khalid
authors: K
authors: El Sayed
authors: Department of Biochemistry, Universidad Central del Caribe. Ave. Laurel #100, Santa Juanita, Bayamon, Puerto Rico, 00956.
authors: Vesna A
authors: VA
authors: Eterovic
authors: Department of Biochemistry, Universidad Central del Caribe. Ave. Laurel #100, Santa Juanita, Bayamon, Puerto Rico, 00956.
authors: Pedro A
authors: PA
authors: Ferchmin
authors: Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267.
authors: Jiukuan
authors: J
authors: Hao
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004224:Diterpenes / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000172:deficiency; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
chemical_list: C569865:(1S,2E,4R,6R,7E,11E)-2,7,11-cembratriene-4,6-diol; D004224:Diterpenes; D018696:Neuroprotective Agents; D005947:Glucose
keywords: 4R cembranoid; inflammation; intercellular adhesion molecule-1; ischemia; neuroprotection; oxygen–glucose deprivation