Acetyl-11-keto-β-boswellic acid ameliorates cognitive deficits and reduces amyloid-β levels in APPswe/PS1dE9 mice through antioxidant and anti-inflammatory pathways
| Autor: | Bo Zhou, Xuan Sun, Jiao Fan, Jiarui Yao, Yanchang Shang, Chao Wei, Guo Yan'e |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Antioxidant medicine.medical_treatment Anti-Inflammatory Agents Inflammation Mice Transgenic Pharmacology medicine.disease_cause Biochemistry Neuroprotection Antioxidants 03 medical and health sciences chemistry.chemical_compound Amyloid beta-Protein Precursor Mice 0302 clinical medicine Cognition Alzheimer Disease Physiology (medical) medicine Amyloid precursor protein Animals Aspartic Acid Endopeptidases biology biology.organism_classification Triterpenes IκBα 030104 developmental biology chemistry biology.protein Boswellia serrata Boswellic acid medicine.symptom Amyloid Precursor Protein Secretases 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | Free radical biologymedicine. 150 |
| ISSN: | 1873-4596 |
| Popis: | Alzheimer's disease (AD) is a complex disease involved oxidative stress and inflammation in its pathogenesis. Acetyl-11-keto-β-boswellic acid (AKBA) is an active triterpenoid compound from extracts of Boswellia serrata, which has been widely used as an antioxidant and anti-inflammatory agent. The present study was to determine whether AKBA, a novel candidate, could protect against cognitive and neuropathological impairments in AD. We found that AKBA treatment resulted in a significant improvement of learning and memory deficits, a dramatic decrease in cerebral amyloid-β (Aβ) levels and plaque burden, a profound alleviation in oxidative stress and inflammation, and a marked reduction in activated glial cells and synaptic defects in the APPswe/PS1dE9 mice. Furthermore, amyloid precursor protein (APP) processing was remarkably suppressed with AKBA treatment by inhibiting beta-site APP cleaving enzyme 1 (BACE1) protein expression to produce Aβ in the APPswe/PS1dE9 mice brains. Mechanistically, AKBA modulated antioxidant and anti-inflammatory pathways via increasing nuclear erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression, and via declining phosphorylation of inhibitor of nuclear factor-kappa B alpha (IκBα) and p65. Collectively, our findings provide evidence that AKBA protects neurons against oxidative stress and inflammation in AD, and this neuroprotective effect involves the Nrf2/HO-1 and nuclear factor-kappa B (NF-κB) signaling pathways. |
| Databáze: | OpenAIRE |
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