Effects of (−)-epicatechin on neuroinflammation and hyperphosphorylation of tau in the hippocampus of aged mice

• Published in: Food & function Vol. 11; no. 12; pp. 1351 - 1361
• Main Authors: Navarrete-Yañez, Viridiana, Garate-Carrillo, Alejandra, Rodriguez, Alonso, Mendoza-Lorenzo, Patricia, Ceballos, Guillermo, Calzada-Mendoza, Claudia, Hogan, Michael C, Villarreal, Francisco, Ramirez-Sanchez, Israel
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 01.12.2020
• Subjects: Aging; Aging (artificial); Alzheimer's disease; Anxiety; Carbonyl compounds; Carbonyls; Caspase-3; Cell death; Cell survival; Cyclooxygenase-2; Cytokines; Epicatechin; Glial fibrillary acidic protein; Growth factors; Hippocampus; Inflammation; Interferon; Interleukin 1 receptor antagonist; Interleukin 1 receptors; Interleukin 10; Interleukin 3; Lymphocytes B; Malondialdehyde; Markers; Mitochondria; Modulators; Myeloid cells; Nerve growth factor; Neuromodulation; Oxidative stress; Proteins; β-Amyloid; γ-Interferon
• DOI: 10.1039/d0fo02438d
• ISSN: 2042-6496

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. (−)-Epicatechin reduces neuroinflammation and Tau-hp, improving memory and learning.