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.

β-Caryophyllene: A Sesquiterpene with Countless Biological Properties

“…All these cellular events determine cell survival and proliferation and angiogenesis [9]. BCP also diminishes the expression of matrix metallopeptidase (MMP-9) and increases the one of occludin, claudin-5, Tight Junction Protein ZO-1 and Growth Associated Protein 43 (GAP-43) [32].…”

A systematic review on the neuroprotective perspectives of beta‐caryophyllene

“…Moreover, in brain microvascular endothelial cells, neurons, and astrocytes, BCAR at 10 μM/L significantly decreased BBB permeability and neuronal apoptosis, mitigated oxidative stress, and reduced the release of inflammatory cytokines. It also down‐regulated Bax and matrix metallopeptidase 9 (MMP‐9) expression, while up‐regulating claudin‐5, occludin, zonula occludens‐1 (ZO‐1), growth associated protein 43 (GAP‐43), and Bcl‐2 expression (Tian et al, ). Recently, BCAR at 0.5, 1.0, 1.5, and 2.0 μM, was found to activate trka receptors and induce neuritogenesis by a mechanism independent of nerve growth factor or cannabinoid receptors in PC12 and SH‐SY5Y neuroblastoma cells (Santos et al, ).…”

Tanshinone IIA Protects Hippocampal Neuronal Cells from Reactive Oxygen Species Through Changes in Autophagy and Activation of Phosphatidylinositol 3-Kinase, Protein Kinas B, and Mechanistic Target of Rapamycin Pathways

“…OGD/R is a classical model of cerebral ischemia in vitro [ 20 , 21 ]. In this study, we have shown that tanshinone IIA can reduce oxidative stress, apoptosis and autophagy that induced by OGD/R treatment in HT-22 cells.…”