A grape seed procyanidin extract inhibits HDAC activity leading to increased Pparα phosphorylation and target‐gene expression
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Scope: Histone deacetylases (HDACs) have emerged as epigenetic regulators of risk factors associated with the metabolic syndrome (MetS), and certain botanical extracts have proven to be potent HDAC inhibitors. Understanding the role of dietary procyanidins in HDAC inhibition is important in exploring the therapeutic potential of natural products. Methods: C57BL/6 mice were gavaged with vehicle (water) or grape seed procyanidin extract (GSPE, 250 mg/kg) and terminated 14 h later. Liver and serum were harvested to assess the effect of GSPE on HDAC activity, histone acetylation, Pparα activity and target‐gene expression, and serum lipid levels. Results: GSPE increased histone acetylation and decreased Class I HDAC activity in vivo, and dose‐dependently inhibited recombinant HDAC2 and 3 activities in vitro. Accordingly, Ppar α gene and phosphorylated protein expression were increased, as were target genes involved in fatty acid catabolism, suggesting increased Pparα activity. Serum fibroblast growth factor 21 (Fgf21) was elevated, and triglyceride levels were reduced by 28%. Conclusion: GSPE regulates HDAC and Pparα activities to modulate lipid catabolism and reduce serum triglycerides in vivo.
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Grape seed proanthocyanidin extract regulates histone acetylation and decreases HDAC activity in both in vivo and in vitro settings, whether used individually or in combination.
“Previous studies have reported that GSPE regulates histone acetylation and decreases HDAC activity in both in vivo and in vitro settings, whether used individually or in combination [23,25].”
From The Synergistic Effect of Proanthocyanidin and HDAC Inhibitor Inhibit Breast Cancer Cell Growth and Promote Apoptosis (2023) · cites this paper as [25]
Section 3.1 (page not supplied) reports increased histone acetylation and reduced Class I HDAC activity in GSPE-treated mouse liver, as well as HDAC inhibition in vitro. It does not report histone acetylation in vitro or test GSPE in combination with another treatment, so those parts of the citing sentence are not supported by this paper. (LLM, conf=0.88)
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References 40 · Cited by 37
- Authors
- Downing, L. E., Ferguson, B. S., Rodriguez, K., & Ricketts, M.
- Affiliations
- University of Nevada, Reno (US)
- Corresponding author
- Ricketts, Marie‐Louise
- Venue
- Molecular Nutrition & Food Research
- Publisher
- Wiley
- Published
- 2016-10-28
- Volume
- 61
- Issue
- 2
- ISSN
- 1613-4125 (ISSN-L)
- 1613-4133
- PMC
- PMC5292052
- OpenAlex
- W2519286715
- Cited by
- 37
- References
- 40
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 3 · 2021: 5 · 2020: 4 · 2019: 4 · 2018: 5 · 2017: 6
- FWCI
- 2.60
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Nutrition & Food Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (P20 GM103650)
- National Institute of Food and Agriculture (Hatch-NEV0738, Hatch-NEV0749, Multistate W-3122)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- grape seed procyanidins, histone deacetylase inhibition, class I HDACs, histone acetylation, metabolic syndrome, fatty acid degradation, FGF21, serum triglycerides, lipid metabolism, dietary polyphenols, HDAC2, HDAC3
- MeSH terms
- Apolipoprotein A-V, Acetylation, Animals, Catechin, Dose-Response Relationship, Drug, Fibroblast Growth Factors, Histone Deacetylases, Histones, Liver, Male, Mice, Inbred C57BL, Phosphorylation, Triglycerides, Proanthocyanidins, Biflavonoids, PPAR alpha, Lipid Metabolism, Histone Deacetylase 2, Histone Deacetylase Inhibitors, Grape Seed Extract
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