Open AccessEffects of (−)-epicatechin on neuroinflammation and hyperphosphorylation of tau in the hippocampus of aged mice
Author(s) -
ViridiavarreteYanez,
Alejandra GarateCarrillo,
Alberto Masaguer Rodríguez,
Patricia MendozaLorenzo,
Guillermo Ceballos,
Claudia C. CalzadaMendoza,
Michael C. Hogan,
Francisco Villarreal,
Israel Ramírez-Sánchez
Publication year - 2020
Publication title -
food and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.145
H-Index - 76
eISSN - 2042-650X
pISSN - 2042-6496
DOI - 10.1039/d0fo02438d
Subject(s) - neuroinflammation , inflammation , hyperphosphorylation , endocrinology , medicine , glial fibrillary acidic protein , oxidative stress , tumor necrosis factor alpha , hippocampus , interleukin , cytokine , chemistry , biochemistry , phosphorylation , immunohistochemistry
Evidence has implicated oxidative stress (OS) and inflammation as drivers of neurodegenerative pathologies. We previously reported on the beneficial effects of (-)-epicatechin (Epi) treatment on aging-induced OS and its capacity to restore modulators of mitochondrial biogenesis in the prefrontal cortex of 26-month-old male mice. In the present study using the same mouse model of aging, we examined the capacity of Epi to mitigate hippocampus OS, inflammation, hyperphosphorylation of tau protein, soluble β-amyloid protein levels, cell survival, memory, anxiety-like behavior levels and systemic inflammation. Mice were subjected to 4 weeks of Epi treatment (1 mg kg -1 day -1 ) and samples of the hippocampus were obtained. Assessments of the OS markers, protein carbonyls, and malondialdehyde levels demonstrated their significant increase (∼3 fold) with aging that were partially suppressed by Epi. The protein levels of the glial fibrillary acidic protein, inflammatory factor 1 (Iba1), pro-inflammatory cytokines, interleukins (IL-1β, IL-3, 5, 6 and 15), cyclooxygenase 2, tumor necrosis factor α, nuclear factor-activated B cells and interferon γ increase with aging and were also significantly decreased with Epi treatment. However, anti-inflammatory cytokines, IL-1ra, IL-10 and 11 decrease with aging and were restored with Epi. Epi also reversed the aging effects on the hyperphosphorylation of tau, increased soluble β-amyloid levels (∼2 fold), cellular death (as per caspase 3 and 9 activity), and reduced nerve growth factor and triggering receptor expressed on myeloid cells 2 levels. Measures of anxiety like-behavior and memory demonstrated improvements with Epi treatment. Indicators of systemic inflammation increase with aging and Epi was capable of decreasing blood inflammatory markers. Altogether, the results show a significant capacity of Epi to mitigate hippocampus OS and inflammation leading to improved brain function.