PMID- 27565895 OWN - NLM STAT- MEDLINE DCOM- 20170614 LR - 20191210 IS - 1471-4159 (Electronic) IS - 0022-3042 (Linking) VI - 139 IP - 5 DP - 2016 Dec TI - beta-Caryophyllene protects in vitro neurovascular unit against oxygen-glucose deprivation and re-oxygenation-induced injury. PG - 757-768 LID - 10.1111/jnc.13833 [doi] AB - beta-Caryophyllene (BCP) mediates neuroprotection in cerebral ischemic animals. The neurovascular unit (NVU) acts as an intricate network to maintain the neuronal homeostatic microenvironment. However, the effects exerted by BCP on NVU remain unclear. Therefore, we established an in vitro NVU model to investigate the effects of BCP on oxygen-glucose deprivation and re-oxygenation (OGD/R)-induced injury. This model involved the co-culture of brain microvascular endothelial cells, neurons, and astrocytes. BCP (10 mumol/L) was applied for 24 h prior to OGD/R and maintained throughout OGD/R. Blood-brain barrier (BBB) integrity and neuronal apoptosis were analyzed. BCP pre-treatment prior to the initiation of OGD/R significantly (i) decreased BBB permeability and neuronal apoptosis, (ii) mitigated oxidative stress damage and the release of inflammatory cytokines, (iii) down-regulated Bax expression, metalloproteinase-9 activity and expression, and (iv) up-regulated claudin-5, occludin, ZO-1, growth-associated protein-43 and Bcl-2 expression. Thus, BCP pre-treatment exerted multiple protective effects on NVU in the context of OGD/R-induced injury. These protective effects potentially occur via reductions in oxidative stress damage and inflammatory cytokines that induce BBB breakdown, subsequently resulting in reduced neuronal apoptosis. The NVU serves as putative therapeutic targets for cerebral ischemia, and the results of this study provide new insights for the application of BCP as a neuroprotective agent. CI - (c) 2016 International Society for Neurochemistry. FAU - Tian, Xiaocui AU - Tian X AD - Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, College of Pharmacy, Chongqing Medical University, Yuzhong District, Chongqing, China. FAU - Peng, Jianhua AU - Peng J AD - Department of Neurosurgery, the Affiliated Hospital of Southwest Medical University, Luzhou, China. FAU - Zhong, Jianjun AU - Zhong J AD - Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China. FAU - Yang, Mei AU - Yang M AD - Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, College of Pharmacy, Chongqing Medical University, Yuzhong District, Chongqing, China. FAU - Pang, Jinwei AU - Pang J AD - Department of Neurosurgery, the Affiliated Hospital of Southwest Medical University, Luzhou, China. FAU - Lou, Jie AU - Lou J AD - Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, College of Pharmacy, Chongqing Medical University, Yuzhong District, Chongqing, China. FAU - Li, Minghang AU - Li M AD - Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, College of Pharmacy, Chongqing Medical University, Yuzhong District, Chongqing, China. FAU - An, Ruidi AU - An R AD - Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, College of Pharmacy, Chongqing Medical University, Yuzhong District, Chongqing, China. FAU - Zhang, Qian AU - Zhang Q AD - Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, College of Pharmacy, Chongqing Medical University, Yuzhong District, Chongqing, China. FAU - Xu, Lu AU - Xu L AD - Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, College of Pharmacy, Chongqing Medical University, Yuzhong District, Chongqing, China. FAU - Dong, Zhi AU - Dong Z AD - Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, College of Pharmacy, Chongqing Medical University, Yuzhong District, Chongqing, China. LA - eng PT - Journal Article DEP - 20160919 PL - England TA - J Neurochem JT - Journal of neurochemistry JID - 2985190R RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - 0 (Neuroprotective Agents) RN - 0 (Polycyclic Sesquiterpenes) RN - 0 (Sesquiterpenes) RN - BHW853AU9H (caryophyllene) RN - IY9XDZ35W2 (Glucose) RN - S88TT14065 (Oxygen) SB - IM MH - Animals MH - Animals, Newborn MH - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology MH - Cell Hypoxia/drug effects/physiology MH - Cells, Cultured MH - Endothelium, Vascular/drug effects/*metabolism MH - Glucose/*deficiency MH - Microvessels/drug effects/metabolism MH - Neurons/drug effects/*metabolism MH - Neuroprotective Agents/pharmacology MH - Oxygen/*metabolism MH - Polycyclic Sesquiterpenes MH - Rats MH - Rats, Sprague-Dawley MH - Sesquiterpenes/*pharmacology OTO - NOTNLM OT - Blood-brain barrier OT - neuronal apoptosis OT - neurovascular unit OT - oxygen-glucose deprivation and re-oxygenation OT - beta-caryophyllene EDAT- 2016/08/28 06:00 MHDA- 2017/06/15 06:00 CRDT- 2016/08/28 06:00 PHST- 2016/06/15 00:00 [received] PHST- 2016/08/15 00:00 [revised] PHST- 2016/08/18 00:00 [accepted] PHST- 2016/08/28 06:00 [pubmed] PHST- 2017/06/15 06:00 [medline] PHST- 2016/08/28 06:00 [entrez] AID - 10.1111/jnc.13833 [doi] PST - ppublish SO - J Neurochem. 2016 Dec;139(5):757-768. doi: 10.1111/jnc.13833. Epub 2016 Sep 19.