Alpha-asarone improves cognitive function of aged rats by alleviating neuronal excitotoxicity via GABAA receptors.
Neuropharmacology
; 162: 107843, 2020 01 01.
Article
em En
| MEDLINE
| ID: mdl-31704273
ABSTRACT
Alzheimer's disease (AD), the most common form of dementia, still lacks effective treatment at present. Alpha-asarone (ASA) is the major compound isolated from the Chinese medicinal herb Acorus gramineus. It has been reported to enhance cognitive function in rodent models, yet its mechanism was not fully understood. In this work, we demonstrated that ASA improved the spatial memory, reduced the neuronal injury, and decreased the level of Aß1-42 in the hippocampus of aged rats. The results also showed that ASA had the neuroprotective effects against glutamate toxicity and decreased cytoplasmic calcium level in primary hippocampal neurons. By comparing the multiple properties of ASA and propofol (PPF) via computer modelling, we speculated that ASA may bind to the PPF binding site of type A gamma (γ)-aminobutyric acid receptors (GABAARs). This was further supported by the whole-cell patch-clamp recording. Our results suggested that ASA, as a GABAAR positive allosteric modulator (PAM), can improve cognitive function of aged rats by alleviating the neuronal overexcitation. Furthermore, the binding mode of ASA on GABAAR may lay a foundation for structure-based drug design in AD therapy.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
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Envelhecimento
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Peptídeos beta-Amiloides
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Cognição
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Receptores de GABA-A
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Fármacos Neuroprotetores
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Memória Espacial
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Hipocampo
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Anisóis
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Neuropharmacology
Ano de publicação:
2020
Tipo de documento:
Article