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

Navarrete‐Yanez, Viridiana; Garate‐Carrillo, Alejandra; Rodríguez, Alberto Masaguer; Mendoza‐Lorenzo, Patricia; Ceballos, Guillermo; Calzada‐Mendoza, Claudia C.; Hogan, Michael C.; Villarreal, Francisco; Ramírez-Sánchez, Israel

doi:10.1039/d0fo02438d

Cited by 20 publications

(15 citation statements)

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“…Sarris et al [ 31 ] nicely described in a review of preclinical studies the anxiolytic profile of the E. arvense, describing a mechanism that primarily involved gamma-aminobutyric acid (GABA), either via direct receptor binding or ionic channel or cell membrane modulation. Additionally, it has been stated that (-)-epicatechin mitigated hippocampus oxidative stress, anxiety-like behavior, and systemic inflammation in aged mice [ 32 ]. Park et al [ 33 ] provided evidence that (-)-epigallocatechin-3-O-gallate reversed caffeine-induced anxiogenic-like effects in an animal model.…”

Section: Resultsmentioning

confidence: 99%

Neuroprotective and Antioxidant Enhancing Properties of Selective Equisetum Extracts

et al. 2021

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The sterile stems belonging to the Equisetum species are often used in traditional medicine of various nations, including Romanians. They are highly efficient in treating urinary tract infections, cardiovascular diseases, respiratory tract infections, and medical skin conditions due to their content of polyphenolic derivatives that have been isolated. In this regard, this study aimed to provide the chemical composition of the extracts obtained from the Equisetum species (E. pratense, E. sylvaticum, E. telmateia) and to investigate the biological action in vitro and in vivo. For the chemical characterization of the analyzed Equisetum species extracts, studies were performed by using ultra-high-performance liquid chromatography (UHPLC-DAD). In vitro evaluation of the antioxidant activity of the plant extracts obtained from these species of Equisetum genus was determined. The neuroprotective activity of these three ethanolic extracts from the Equisetum species using zebrafish tests was determined in vivo. All obtained results were statistically significant. The results indicate that E. sylvaticum extract has a significant antioxidant activity; whereas, E. pratense extract had anxiolytic and antidepressant effects significantly higher than the other two extracts used. All these determinations indicate promising results for the antioxidant in vitro tests and neuroprotective activity of in vivo tests, particularly mediated by their active principles.

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Section: Resultsmentioning

confidence: 99%

Neuroprotective and Antioxidant Enhancing Properties of Selective Equisetum Extracts

et al. 2021

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“…However, EC did not increase inhibitory phosphorylation of GSK3β at Ser9 either in vivo (Figures 2A,B) or in vitro (Figures 2C,D). This contrasts with reported EC upregulation of the Akt/GSK3β pathway in aged (Navarrete-Yañez et al, 2020) and in APP/PS1 mice (Zhang et al, 2016). The lack of effect in rTg4510 mice could be related in some-way to the use of tauopathy models, as Grape seed polyphenolic extract (GSPE) also failed to increase activity of the Akt/GSK3beta pathway in TMHT tau mice (Wang et al, 2010).…”

Section: Discussionmentioning

confidence: 75%

“…EC has well characterized signaling actions in neural cells ( Schroeter et al, 2007 ; Bahia et al, 2008 ) and is a promising intervention for AD due to its low toxicity profile ( Ottaviani et al, 2015 ) and potential for multi-modal targeting ( Hole and Williams, 2020 ). EC has been shown to improve vascular function and cognition in humans ( Bernatova, 2018 ; Haskell-Ramsay et al, 2018 ), reduce oxidative stress and up-regulate neuroprotective pathways ( Schroeter et al, 2001 ; Spencer et al, 2001 ; Shah et al, 2010 ; Rendeiro et al, 2013 ; Zhang et al, 2016 ; Navarrete-Yañez et al, 2020 ). With respect to AD pathology, intervention with EC has been shown to inhibit APP processing in primary cortical neurons ( Cox et al, 2015 ) and reduce Aβ burden in APP SWE /PS1 mouse models ( Zeng et al, 2014 ; Cox et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

“…There is some evidence to suggest that flavan-3-ol administration could influence tau pathology, as grape seed and lychee extracts reduce tau phosphorylation in vivo ( Wang et al, 2010 ; Santa-Maria et al, 2012 ; Chen et al, 2019 ), and EC reduced basal tau phosphorylation in aged mice ( Navarrete-Yañez et al, 2020 ). The key tau kinase GSK3β is a promising target for EC as it can increase Akt phosphorylation ( Schroeter et al, 2007 ), which regulates GSK3β activity by inhibitory phosphorylation at Ser9.…”

Section: Introductionmentioning

confidence: 99%

“…The key tau kinase GSK3β is a promising target for EC as it can increase Akt phosphorylation ( Schroeter et al, 2007 ), which regulates GSK3β activity by inhibitory phosphorylation at Ser9. EC intervention in aged ( Navarrete-Yañez et al, 2020 ) and APP/PS1 ( Zhang et al, 2016 ) mice has been shown to increase phosphorylation of GSK3β via Akt, but this has not been explored in a mouse model of tauopathy.…”

Section: Introductionmentioning

confidence: 99%

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Oral (−)-Epicatechin Inhibits Progressive Tau Pathology in rTg4510 Mice Independent of Direct Actions at GSK3β

et al. 2021

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Aggregation of the microtubule-associated protein tau into paired helical filaments (PHFs) and neurofibrillary tangles is a defining characteristic of Alzheimer’s Disease. Various plant polyphenols disrupt tau aggregation in vitro but display poor bioavailability and low potency, challenging their therapeutic translation. We previously reported that oral administration of the flavonoid (−)-epicatechin (EC) reduced Amyloid-β (Aβ) plaque pathology in APP/PS1 transgenic mice. Here, we investigated whether EC impacts on tau pathology, independent of actions on Aβ, using rTg4510 mice expressing P301L mutant tau. 4 and 6.5 months old rTg4510 mice received EC (∼18 mg/day) or vehicle (ethanol) via drinking water for 21 days and the levels of total and phosphorylated tau were assessed. At 4 months, tau appeared as two bands of ∼55 kDa, phosphorylated at Ser262 and Ser396 and was unaffected by exposure to EC. At 6.5 months an additional higher molecular weight form of tau was detected at ∼64 kDa which was phosphorylated at Ser262, Ser396 and additionally at the AT8 sites, indicative of the presence of PHFs. EC consumption reduced the levels of the ∼64 kDa tau species and inhibited phosphorylation at Ser262 and AT8 phosphoepitopes. Regulation of the key tau kinase glycogen synthase kinase 3β (GSK3β) by phosphorylation at Ser9 was not altered by exposure to EC in mice or primary neurons. Furthermore, EC did not significantly inhibit GSK3β activity at physiologically-relevant concentrations in a cell free assay. Therefore, a 21-day intervention with EC inhibits or reverses the development of tau pathology in rTg4510 mice independently of direct inhibition of GSK3β.

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Phytonutraceuticals Modulate Cell Survival Signaling and Regulate Sympathetic Innervation in Aging and Disease

Seetharaman,

Vasantharekha,

Balu

et al. 2024

Neuroprotective Effects of Phytochemicals in Brain Ageing

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

Abstract: 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...

Cited by 20 publications

References 39 publications

Neuroprotective and Antioxidant Enhancing Properties of Selective Equisetum Extracts

Neuroprotective and Antioxidant Enhancing Properties of Selective Equisetum Extracts

Oral (−)-Epicatechin Inhibits Progressive Tau Pathology in rTg4510 Mice Independent of Direct Actions at GSK3β

Phytonutraceuticals Modulate Cell Survival Signaling and Regulate Sympathetic Innervation in Aging and Disease

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