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Prolonged Treatment with Centella asiatica Improves Memory, Reduces Amyloid-ß Pathology, and Activates NRF2-Regulated Antioxidant Response Pathway in 5xFAD Mice.
Zweig, Jonathan A; Brandes, Mikah S; Brumbach, Barbara H; Caruso, Maya; Wright, Kirsten M; Quinn, Joseph F; Soumyanath, Amala; Gray, Nora E.
Afiliación
  • Zweig JA; Department of Neurology, Oregon Health & Science University, Portland, OR, USA.
  • Brandes MS; Department of Neurology, Oregon Health & Science University, Portland, OR, USA.
  • Brumbach BH; Biostatistics & Design Program Core, Oregon Health & Science University, Portland, OR, USA.
  • Caruso M; Department of Neurology, Oregon Health & Science University, Portland, OR, USA.
  • Wright KM; Department of Neurology, Oregon Health & Science University, Portland, OR, USA.
  • Quinn JF; Department of Neurology, Oregon Health & Science University, Portland, OR, USA.
  • Soumyanath A; Department of Neurology and Parkinson's Disease Research Education and Clinical Care Center (PADRECC), VA Portland Healthcare System, Portland, OR, USA.
  • Gray NE; Department of Neurology, Oregon Health & Science University, Portland, OR, USA.
J Alzheimers Dis ; 81(4): 1453-1468, 2021.
Article en En | MEDLINE | ID: mdl-33935097
BACKGROUND: The medicinal herb Centella asiatica has been long been used for its neuroprotective and cognitive enhancing effects. We have previously shown that two weeks of treatment with a water extract of Centella asiatica (CAW) improves cognition and activates the endogenous antioxidant response pathway without altering amyloid-ß (Aß) plaque burden. OBJECTIVE: Here, we assess the effect of long-term treatment of CAW in the 5xFAD mouse model of Aß accumulation. METHODS: Four-month-old 5xFAD mice were treated with CAW in their drinking water (2 g/L) for three months at which point they underwent cognitive testing as well as analysis of Aß plaque levels and antioxidant and synaptic gene expression. In order to confirm the involvement of the antioxidant regulatory transcription factor NRF2 on the effects of CAW on synaptic plasticity, neurons isolated from 5xFAD mice were also treated with CAW and the targeted inhibitor ML385. RESULTS: Three months of treatment with CAW improved spatial and contextual memory as well as executive function in 5xFAD mice. This improvement was accompanied by increased antioxidant gene expression and a decrease in Aß plaque burden relative to untreated 5xFAD animals. In isolated neurons, treatment with ML385 blocked the effects of CAW on dendritic arborization and synaptic gene expression. CONCLUSION: These results suggest that prolonged CAW exposure could be beneficial in Alzheimer's disease and that these effects likely involve NRF2 activation. Moreover, these findings suggest that targeting NRF2 itself may be a relevant therapeutic strategy for improving synaptic plasticity and cognitive function in Alzheimer's disease.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Extractos Vegetales / Péptidos beta-Amiloides / Centella / Factor 2 Relacionado con NF-E2 / Hipocampo / Memoria Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Alzheimers Dis Asunto de la revista: GERIATRIA / NEUROLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Extractos Vegetales / Péptidos beta-Amiloides / Centella / Factor 2 Relacionado con NF-E2 / Hipocampo / Memoria Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Alzheimers Dis Asunto de la revista: GERIATRIA / NEUROLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos