ArticleNutrition & metabolism2021
Ferulic acid alleviates lipotoxicity-induced hepatocellular death through the SIRT1-regulated autophagy pathway and independently of AMPK and Akt in AML-12 hepatocytes.
Article in Nutrition & metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- GDF15 Improves Renal Injury Induced by Ectopic Lipid Deposition via AMPK/SIRT1 Pathway-Mediated Autophagy.Metabolites · 2026Article
- Ferulic acid restores mitochondrial dynamics and autophagy via AMPK signaling pathway in a palmitate-induced hepatocyte model of metabolic syndrome.Scientific reports · 2024Article
- The micro-743a-3p-GSTM1 pathway is an endogenous protective mechanism against alcohol-related liver disease in mice.Cellular & molecular biology letters · 2024Article
- Rational Design of Multifunctional Ferulic Acid Derivatives Aimed for Alzheimer's and Parkinson's Diseases.Antioxidants (Basel, Switzerland) · 2023Article
- Influence of trans-ferulic acid on the quality of ram semen upon cold preservation.Veterinary medicine and science · 2023Article
- Molecular mechanism and research progress on pharmacology of ferulic acid in liver diseases.Frontiers in pharmacology · 2023Review
- Nutraceutical activation of Sirt1: a review.Open heart · 2022Review
- Nutraceutical Prevention of Diabetic Complications-Focus on Dicarbonyl and Oxidative Stress.Current issues in molecular biology · 2022Review
- Review
- Targeting Sirt1, AMPK, Nrf2, CK2, and Soluble Guanylate Cyclase with Nutraceuticals: A Practical Strategy for Preserving Bone Mass.International journal of molecular sciences · 2022Review
- Article
- Ferulic acid and berberine, via Sirt1 and AMPK, may act as cell cleansing promoters of healthy longevity.Open heart · 2022Review
- Review
- Nutraceutical and Dietary Strategies for Up-Regulating Macroautophagy.International journal of molecular sciences · 2022Review
- Cimifugin Ameliorates Lipotoxicity-Induced Hepatocyte Damage and Steatosis through TLR4/p38 MAPK- and SIRT1-Involved Pathways.Oxidative medicine and cellular longevity · 2022Article
- Maintaining Effective Beta Cell Function in the Face of Metabolic Syndrome-Associated Glucolipotoxicity-Nutraceutical Options.Healthcare (Basel, Switzerland) · 2021Review
- Recent Advances in Biological Activity, New Formulations and Prodrugs of Ferulic Acid.International journal of molecular sciences · 2021Review
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Authors and funding
11 authors.
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Abstract
backgroundLipotoxicity-induced cell death plays a detrimental role in the pathogenesis of metabolic diseases. Ferulic acid, widespread in plant-based food, is a radical scavenger with multiple bioactivities. However, the benefits of ferulic acid against hepatic lipotoxicity are largely unclear. Here, we investigated the protective effect of ferulic acid against palmitate-induced lipotoxicity and clarified its potential mechanisms in AML-12 hepatocytes.
methodsAML-12 mouse hepatocytes were exposed to palmitate to mimic lipotoxicity. Different doses (25, 50, and 100 μM) of ferulic acid were added 2 h before palmitate treatment. Cell viability was detected by measuring lactate dehydrogenase release, nuclear staining, and the expression of cleaved-caspase-3. Intracellular reactive oxygen species content and mitochondrial membrane potential were analysed by fluorescent probes. The potential mechanisms were explored by molecular biological methods, including Western blotting and quantitative real-time PCR, and were further verified by siRNA interference.
resultsOur data showed that ferulic acid significantly inhibited palmitate-induced cell death, rescued mitochondrial membrane potential, reduced reactive oxygen species accumulation, and decreased inflammatory factor activation, including IL-6 and IL-1beta. Ferulic acid significantly stimulated autophagy in hepatocytes, whereas autophagy suppression blocked the protective effect of ferulic acid against lipotoxicity. Ferulic acid-activated autophagy, which was triggered by SIRT1 upregulation, was mechanistically involved in its anti-lipotoxicity effects. SIRT1 silencing blocked most beneficial changes induced by ferulic acid.
conclusionsWe demonstrated that the phytochemical ferulic acid, which is found in plant-based food, protected against hepatic lipotoxicity, through the SIRT1/autophagy pathway. Increased intake of ferulic acid-enriched food is a potential strategy to prevent and/or improve metabolic diseases with lipotoxicity as a typical pathological feature.
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