title: β-Caryophyllene protects in vitro neurovascular unit against oxygen-glucose deprivation and re-oxygenation-induced injury.
abstract: β-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 μmol/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.
authors: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, College of Pharmacy, Chongqing Medical University, Yuzhong District, Chongqing, China.
authors: Xiaocui
authors: X
authors: Tian
authors: Department of Neurosurgery, the Affiliated Hospital of Southwest Medical University, Luzhou, China.
authors: Jianhua
authors: J
authors: Peng
authors: Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors: Jianjun
authors: J
authors: Zhong
authors: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, College of Pharmacy, Chongqing Medical University, Yuzhong District, Chongqing, China.
authors: Mei
authors: M
authors: Yang
authors: Department of Neurosurgery, the Affiliated Hospital of Southwest Medical University, Luzhou, China.
authors: Jinwei
authors: J
authors: Pang
authors: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, College of Pharmacy, Chongqing Medical University, Yuzhong District, Chongqing, China.
authors: Jie
authors: J
authors: Lou
authors: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, College of Pharmacy, Chongqing Medical University, Yuzhong District, Chongqing, China.
authors: Minghang
authors: M
authors: Li
authors: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, College of Pharmacy, Chongqing Medical University, Yuzhong District, Chongqing, China.
authors: Ruidi
authors: R
authors: An
authors: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, College of Pharmacy, Chongqing Medical University, Yuzhong District, Chongqing, China.
authors: Qian
authors: Q
authors: Zhang
authors: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, College of Pharmacy, Chongqing Medical University, Yuzhong District, Chongqing, China.
authors: Lu
authors: L
authors: Xu
authors: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, College of Pharmacy, Chongqing Medical University, Yuzhong District, Chongqing, China.
authors: Zhi
authors: Z
authors: Dong
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005947:Glucose / Q000172:deficiency*; D055806:Microvessels / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism*; D000081223:Polycyclic Sesquiterpenes; D051381:Rats; D017207:Rats, Sprague-Dawley; D012717:Sesquiterpenes / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018696:Neuroprotective Agents; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes; C024714:caryophyllene; D005947:Glucose; D010100:Oxygen
keywords: Blood-brain barrier; neuronal apoptosis; neurovascular unit; oxygen-glucose deprivation and re-oxygenation; β-caryophyllene