Acetyl-11-keto-β-boswellic acid (AKBA) Attenuates Oxidative Stress, Inflammation, Complement Activation and Cell Death in Brain Endothelial Cells Following OGD/Reperfusion

  • Saif AhmadEmail author
  • Shah Alam Khan
  • Adam Kindelin
  • Tasha Mohseni
  • Kanchan Bhatia
  • Md Nasrul Hoda
  • Andrew F. DucruetEmail author
Original Paper


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.


bEND.3 AKBA OGD BBB Inflammation Complement C3a receptor 



This study was supported by the Barrow Neurological Foundation (BNF).

Compliance with Ethical Standards

Conflict of interest

None of the authors have any conflicts of interest to disclose.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of NeurosurgeryBarrow Neurological Institute, St. Joseph’s Hospital and Medical Center (SJHMC), Dignity HealthPhoenixUSA
  2. 2.Department of PharmacyOman Medical CollegeMuscatSultanate of Oman
  3. 3.Department of NeurologyBarrow Neurological Institute, St. Joseph’s Hospital and Medical Center (SJHMC), Dignity HealthPhoenixUSA
  4. 4.Department of NeurobiologyBarrow Neurological Institute, St. Joseph’s Hospital and Medical Center (SJHMC), Dignity HealthPhoenixUSA

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