ArticleFrontiers in neuroscience2021
Integrated Multi-Omic Analyses of the Genomic Modifications by Gut Microbiome-Derived Metabolites of Epicatechin, 5-(4'-Hydroxyphenyl)-γ-Valerolactone, in TNFalpha-Stimulated Primary Human Brain Microvascular Endothelial Cells.
Article in Frontiers in neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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Who cites it
13 citing papers in PubMed, 24 citations in OpenAlex.
- Polyphenols Limit Cerebral Endothelial Cell Dysfunction Under Inflammatory Conditions Related to Oral and Gut Microbiota.Nutrients · 2026Article
- (-)-Epicatechin and inflammation: Unraveling the role of microbial metabolites and interindividual metabolic variability.Frontiers in microbiology · 2026Review
- The Gut-Brain Axis in Alzheimer's Disease: Exploring Microbial Influences and Therapeutic Strategies.Molecular neurobiology · 2025Review
- From the gut to the brain: the long journey of phenolic compounds with neurocognitive effects.Nutrition reviews · 2025Review
- Plant Polyphenols as Heart's Best Friends: From Health Properties, to Cellular Effects, to Molecular Mechanisms of Action.International journal of molecular sciences · 2025Review
- The Molecular Bases of Anti-Oxidative and Anti-Inflammatory Properties of Paraoxonase 1.Antioxidants (Basel, Switzerland) · 2024Review
- Review
- Coffee polyphenols ameliorate early-life stress-induced cognitive deficits in male mice.Neurobiology of stress · 2024Article
- The Potential of Flavonoids and Flavonoid Metabolites in the Treatment of Neurodegenerative Pathology in Disorders of Cognitive Decline.Antioxidants (Basel, Switzerland) · 2023Review
- Circulating (Poly)phenol Metabolites: Neuroprotection in a 3D Cell Model of Parkinson's Disease.Molecular nutrition & food research · 2022Article
- Alzheimer's Disease: An Update and Insights Into Pathophysiology.Frontiers in aging neuroscience · 2022Review
- Anthocyanin-rich extract from black beans exerts anti-diabetic effects in rats through a multi-genomic mode of action in adipose tissue.Frontiers in nutrition · 2022Article
- The Potential Role of Polyphenols in Oxidative Stress and Inflammation Induced by Gut Microbiota in Alzheimer's Disease.Antioxidants (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cerebral blood vessels are lined with endothelial cells and form the blood-brain barrier. Their dysfunction constitutes a crucial event in the physiopathology of neurodegenerative disorders and cognitive impairment. Epicatechin can improve cognitive functions and lower the risk for Alzheimer's disease or stroke. However, molecular mechanisms of epicatechin on brain vascular endothelium are still unexplored. The objective of this study was to investigate the biological effects of gut microbiome-derived metabolites of epicatechin, 5-(4'-Hydroxyphenyl)-γ-valerolactone-3'-sulfate and 5-(4'-Hydroxyphenyl)-γ-valerolactone-3'-O-glucuronide, in TNF-α-stimulated human brain microvascular endothelial cells at low (nM) concentrations by evaluating their multi-omic modification (expression of mRNA, microRNA, long non-coding RNAs, and proteins). We observed that metabolites are biologically active and can simultaneously modulate the expression of protein-coding and non-coding genes as well as proteins. Integrative bioinformatics analysis of obtained data revealed complex networks of genomics modifications by acting at different levels of regulation. Metabolites modulate cellular pathways including cell adhesion, cytoskeleton organization, focal adhesion, signaling pathways, pathways regulating endothelial permeability, and interaction with immune cells. This study demonstrates multimodal mechanisms of action by which epicatechin metabolites could preserve brain vascular endothelial cell integrity, presenting mechanisms of action underlying epicatechin neuroprotective properties.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.