Abstract
Oxidative stress is well known to play a pivotal role in cerebral ischemia–reperfusion injury. The nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway has been considered a potential target for neuroprotection in stroke. 11-Keto-β-boswellic acid (KBA) is a triterpenoid compound from extracts of Boswellia serrata. The aim of the present study was to determine whether KBA, a novel Nrf2 activator, can protect against cerebral ischemic injury. Middle cerebral artery occlusion (MCAO) was operated on male Sprague–Dawley rats. KBA (25 mg/kg) applied 1 h after reperfusion significantly reduced infarct volumes and apoptotic cells as well as increased neurologic scores at 48 h after reperfusion. Meanwhile, posttreatment with KBA significantly decreased malondialdehyde (MDA) levels, restored the superoxide dismutase (SOD) activity, and increased the protein Nrf2 and HO-1 expression in brain tissues. In primary cultured astrocytes, KBA increased the Nrf2 and HO-1 expression, which provided protection against oxygen and glucose deprivation (OGD)-induced oxidative insult. But knockdown of Nrf2 or HO-1 attenuated the protective effect of KBA. In conclusion, these findings provide evidence that the neuroprotection of KBA against oxidative stress-induced ischemic injury involves the Nrf2/HO-1 pathway.
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Abbreviations
- KBA:
-
11-Keto-β-boswellic acid
- ARE:
-
Antioxidant response elements
- CBF:
-
Cerebral blood flow
- EMSA:
-
Electrophoresis mobility shift assay
- GPx:
-
Glutathione peroxidase
- I/R:
-
Ischemia–reperfusion
- HE:
-
Hematoxylin and eosin
- HO-1:
-
Heme oxygenase-1
- Keap1:
-
Kelch-like ECH-associated protein 1
- MCAO:
-
Middle cerebral artery occlusion
- MDA:
-
Malondialdehyde
- MTT:
-
3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide
- Nrf2:
-
Nuclear factor erythroid-2-related factor 2
- OGD:
-
Oxygen and glucose deprivation
- PBS:
-
Phosphate-buffered saline
- ROS:
-
Reactive oxygen species
- SD:
-
Standard deviation
- siRNA:
-
Small interfering RNA
- SOD:
-
Superoxide dismutase
- TTC:
-
2,3,5-Triphenyltetrazolium chloride
- TUNEL:
-
Terminal deoxynucleotidyl transferase dUTP nick end labeling
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Acknowledgments
This work received the support of the grant from the Key Technologies for New Drug Innovation and Development of China (No. 2011ZXJ09202-13; No. 2012BAK25B00) and National Natural Science Foundation of China (No.81373947; No.81201985).
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The authors declare that they have no conflict of interest.
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Ding, Y., Chen, M., Wang, M. et al. Posttreatment with 11-Keto-β-Boswellic Acid Ameliorates Cerebral Ischemia–Reperfusion Injury: Nrf2/HO-1 Pathway as a Potential Mechanism. Mol Neurobiol 52, 1430–1439 (2015). https://doi.org/10.1007/s12035-014-8929-9
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DOI: https://doi.org/10.1007/s12035-014-8929-9