ArticleNutrients2018
Ellagic Acid Alleviates Hepatic Oxidative Stress and Insulin Resistance in Diabetic Female Rats.
Article in Nutrients, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 104 citations in OpenAlex.
- Potential effect of tropical fruits Phyllanthus emblica L. for the prevention and management of type 2 diabetic complications: a systematic review of recent advances.European journal of nutrition · 2021Pooled it
- A randomized double-blind clinical trial investigating the effects of ellagic acid on glycemic status, liver enzymes, and oxidative stress in patients with non-alcoholic fatty liver disease.BMC complementary medicine and therapies · 2025Trial
- Ameliorative effect of curcumin and/or cerium oxide nanoparticles on diabetes of rats: biochemical, molecular, and pathological insights.Scientific reports · 2026Article
- Antimicrobial Activity ofCurrent issues in molecular biology · 2026Article
- Chestnut-derived ellagitannins (FT50) protect against western diet-induced metabolic dysfunction and preserve beta cell function in mice.Frontiers in endocrinology · 2026Article
- Therapeutic Potential of Ellagic Acid in Liver Diseases.Molecules (Basel, Switzerland) · 2025Review
- Therapeutic Potential ofAntioxidants (Basel, Switzerland) · 2025Article
- Design and Optimization of a Second-Generation Extruded Snack Using Carrot Waste, Blue Corn Flour, and Ellagic Acid as Functional Ingredients.Foods (Basel, Switzerland) · 2025Article
- Phenolic Acids from Fruit By-Products as Therapeutic Agents for Metabolic Syndrome: A Review.International journal of molecular sciences · 2025Review
- Hypoglycemic effect of peony flowers polyphenols based on gut microbiota and metabolomics.Frontiers in nutrition · 2025Article
- Harnessing Prebiotics to Improve Type 2 Diabetes Outcomes.Nutrients · 2024Review
- Clinically Effective Molecules of Natural Origin for Obesity Prevention or Treatment.International journal of molecular sciences · 2024Review
- Ultra-High-Performance Liquid Chromatography-Electrospray Ionization-High-Resolution Mass Spectrometry for Distinguishing the Origin of Ellagic Acid Extracts: Pomegranate Peels or Gallnuts.Molecules (Basel, Switzerland) · 2024Article
- Mechanism of Action and Related Natural Regulators of Nrf2 in Nonalcoholic Fatty Liver Disease.Current drug delivery · 2024Review
- The Interconnection between Hepatic Insulin Resistance and Metabolic Dysfunction-Associated Steatotic Liver Disease-The Transition from an Adipocentric to Liver-Centric Approach.Current issues in molecular biology · 2023Review
- Article
- Ellagic Acid and Its Metabolites as Potent and Selective Allosteric Inhibitors of Liver Pyruvate Kinase.Nutrients · 2023Article
- Spotlight on iron and ferroptosis: research progress in diabetic retinopathy.Frontiers in endocrinology · 2023Review
- Review
- Ellagic acid protects against non-alcoholic fatty liver disease in streptozotocin-diabetic rats by activating AMPK.Pharmaceutical biology · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Non-alcoholic fatty liver disease (NAFLD) affects more than 70% of patients with type 2 diabetes mellitus (T2DM) and has become one of the most common metabolic liver diseases worldwide. To date, treatments specifically targeting NAFLD do not exist. Oxidative stress and insulin resistance have been implicated in the pathogenesis of NAFLD in diabetes. Accordingly, the goal of this present study was to determine whether Ellagic acid (EA), a natural antioxidant polyphenol found in berries and nuts, mitigates hepatic oxidative stress and insulin resistance in T2DM rats, and thus alleviates NAFLD. Using adult female Goto Kakizaki (GK) rats, a non-obese and spontaneous model of T2DM, we found that EA treatment significantly lowered fasting blood glucose and reduced insulin resistance, as shown by a 21.8% reduction in the homeostasis model assessment index of insulin resistance (HOMA-IR), while triglyceride and total cholesterol levels remained unchanged. Increased hepatic lipid accumulation and oxidative stress present in diabetic GK rats was markedly reduced with EA treatment. This effect was associated with a downregulation of the NADPH oxidase subunit, p47-phox, and overexpression of NF-E2-related factor-2 (NRF2). Moreover, EA was able to decrease the hepatic expression of hypoxia-inducible factor (HIF-α), a transcription factor linked to hypoxia and hepatic steatosis. We further showed that EA treatment activated an insulin signaling pathway in the liver, as evidenced by increased levels of phosphorylated Akt (Ser 473). In conclusion, our results demonstrate that EA diminishes blood glucose levels and potently suppress NAFLD in diabetic rats via mechanisms that involve reductions in p47-phox and HIF-α, upregulation of NRF2 and enhancement of the Akt signaling pathway in the liver. Together, these results reveal that EA improves hepatic insulin sensitivity and lipid metabolism as a result of its antioxidant effects. This implies an anti-diabetic effect of EA with beneficial effects for the treatment of hepatic complications in T2DM.
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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.