Acetyl-11-keto-β-boswellic acid (AKBA) Attenuates Oxidative Stress, Inflammation, Complement Activation and Cell Death in Brain Endothelial Cells Following OGD/Reperfusion
Document Type
Article
Abstract
© 2019, Springer Science+Business Media, LLC, part of Springer Nature. Brain endothelial cells play an important role in maintaining blood flow homeostasis in the brain. Cerebral ischemia is a major cause of endothelial dysfunction which can disrupt the blood–brain barrier (BBB). Oxygen–glucose deprivation (OGD)/reperfusion promote cell death and BBB breakdown in brain endothelial cells. Acetyl-11-keto-β-boswellic acid (AKBA), a biologically active phytoconstituent of the medicinal plant Boswellia serrata, has been shown to be protective against various inflammatory diseases as well as ischemic brain injury. The molecular mechanisms underlying these beneficial characteristics of AKBA are poorly understood. We subjected bEND.3 cells to OGD/reperfusion to investigate the protective role of AKBA in this model. We found that AKBA treatment attenuated endothelial cell death and oxidative stress assessed by means of TUNEL assay, cleaved-caspase-3, and dihydroethidium (DHE) staining. Furthermore, OGD downregulated tight junction proteins ZO-1 and Occludin levels, and increased the expressions of inflammatory cytokines TNF-α, ICAM-1, and complement C3a receptor (C3aR). We also noticed the increased phosphorylation of ERK 1/2 in bEND.3 cells in OGD group. AKBA treatment significantly attenuated expression levels of these inflammatory proteins and prevented the degradation of ZO-1 and Occludin following OGD. In conclusion, AKBA treatment provides protection against endothelial cell dysfunction following OGD by attenuating oxidative stress and inflammation.
Keywords
AKBA, BBB, bEND.3, Complement C3a receptor, Inflammation, OGD
Publication Date
12-1-2019
Publication Title
NeuroMolecular Medicine
ISSN
15351084
E-ISSN
15591174
Volume
21
Issue
4
First Page
505
Last Page
516
PubMed ID
31515728
Digital Object Identifier (DOI)
10.1007/s12017-019-08569-z
Recommended Citation
Ahmad, Saif; Khan, Shah Alam; Kindelin, Adam; Mohseni, Tasha; Bhatia, Kanchan; Hoda, Md Nasrul; and Ducruet, Andrew F., "Acetyl-11-keto-β-boswellic acid (AKBA) Attenuates Oxidative Stress, Inflammation, Complement Activation and Cell Death in Brain Endothelial Cells Following OGD/Reperfusion" (2019). Translational Neuroscience. 498.
https://scholar.barrowneuro.org/neurobiology/498