Integrative evidence construction for resveratrol treatment of nonalcoholic fatty liver disease: preclinical and clinical meta-analyses

Abstract

Background: Resveratrol, a polyphenol found in various plants, is known for its diverse bioactivities and has been explored in relation to nonalcoholic fatty liver disease (NAFLD). However, no high-quality evidence exists regarding its efficacy.Objective: a meta-analysis was conducted to evaluate the potential efficacy of resveratrol in treating nonalcoholic fatty liver disease by analyzing both preclinical studies and clinical trials.Method: PubMed, Embase and Web of Science were searched for the included literature with the criteria for screening. Quantitative synthesis and meta-analyses were performed by STATA 16.0.Results: Twenty-seven studies were included, and the results indicated that resveratrol effectively improved liver function, reduced fatty liver indicators, and affected other indices in preclinical studies. The effective dosage ranged from 50 mg/kg-200 mg/kg, administered over a period of 4–8 weeks. While there were inconsistencies between clinical trials and preclinical research, both study types revealed that resveratrol significantly reduced tumor necrosis factor-α levels, further supporting its protective effect against nonalcoholic fatty liver disease. Additionally, resveratrol alleviated nonalcoholic fatty liver disease primarily via AMPK/Sirt1 and anti-inflammatory signaling pathways.Conclusion: Current meta-analysis could not consistently verify the efficacy of resveratrol in treating nonalcoholic fatty liver disease, but demonstrated the liver-protective effects on nonalcoholic fatty liver disease. The large-sample scale and single region RCTs were further needed to investigate the efficacy.

Updated mechanisms of MASLD pathogenesis

“…Resveratrol effectively decreases the levels of fatty liver biomarkers and confers protection against MASLD in animal studies. Nonetheless, further studies are needed to determine its clinical applicability [ 148 ]. Breviscapine directly inhibits the TGF-β-activated kinase 1 (TAK1) and is deemed a possible candidate for the treatment of MASH [ 149 ].…”

Impact of Transgenerational Nutrition on Nonalcoholic Fatty Liver Disease Development: Interplay between Gut Microbiota, Epigenetics and Immunity

“…In clinical investigations, the implication of resveratrol and GLP-1 (Glucagon-like peptide-1) receptor agonists, both of which can activate SIRT1, in NAFLD treatment has been investigated. Clinical meta-analyses have shown that resveratrol intake ameliorated NAFLD primarily through AMPK/SIRT1 and anti-inflammatory pathways [112]. The GLP-1 receptor agonist semaglutide improves several pathological characteristics of NAFLD, including reduced steatosis, lobular inflammation, hepatocellular ballooning, and alleviation of NASH progression Emerging evidence suggests the therapeutic potential of correcting dysregulated epigenetic modifications in NAFLD.…”