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

Abstract

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.

• Authors: Saif Ahmad, Shah Alam Khan, Adam Kindelin, Tasha Mohseni, Kanchan Bhatia, Md Nasrul Hoda, Andrew F Ducruet
• Journal: Neuromolecular medicine (Neuromolecular Med) Vol. 21 Issue 4 Pg. 505-516 (12 2019) ISSN: 1559-1174 [Electronic] United States
• PMID: 31515728 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Antioxidants
• Complement Inactivating Agents
• Plant Extracts
• Reactive Oxygen Species
• Triterpenes
• acetyl-11-ketoboswellic acid
• Glucose
• Oxygen

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Antioxidants (pharmacology)
• Apoptosis (drug effects)
• Boswellia (chemistry)
• Cell Hypoxia
• Complement Activation (drug effects)
• Complement Inactivating Agents (pharmacology)
• DNA Damage
• Endothelial Cells (cytology, drug effects, metabolism)
• Glucose (pharmacology)
• Hypoxia-Ischemia, Brain (metabolism)
• Inflammation
• MAP Kinase Signaling System (drug effects)
• Mice
• Oxidative Stress (drug effects)
• Oxygen (pharmacology)
• Plant Extracts (chemistry)
• Plants, Medicinal (chemistry)
• Reactive Oxygen Species (analysis)
• Triterpenes (pharmacology)