Ellagic acid as potential therapeutic compound for diabetes and its complications: a systematic review from bench to bed.

Diabetes mellitus (DM) is a worldwide-concerning disease with a rising prevalence. There are many ongoing studies aimed at finding new and effective treatments. Ellagic acid (EA) is a natural polyphenolic compound abundant in certain fruits and vegetables. It is the objective of this investigation to assess the effectiveness and preventive mechanisms of EA on DM and associated complications. This systematic review used PubMed, Scopus, and Google Scholar as search databases using a predetermined protocol from inception to June 2024. We assessed all related English studies, including in vitro, in vivo, and clinical trials. EA counteracted DM and its complications by diminishing inflammation, oxidative stress, hyperglycemia, apoptosis, insulin resistance, obesity, lipid profile, and histopathological alterations. Several mechanisms contributed to the anti-diabetic effect of EA, the most significant being the upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), peroxisome proliferator-activated receptor gamma (PPAR-γ), protein kinase B, and downregulation of nuclear factor-kappa-B (NF-κB) gene expression. EA also revealed protective effects against diabetes complications, such as diabetic-induced hepatic damage, testicular damage, endothelial dysfunction, muscle dysfunction, retinopathy, nephropathy, cardiomyopathy, neuropathy, and behavioral deficit. Administration of EA could have various protective effects in preventing, treating, and alleviating DM and its complications. Although it could be considered a cost-effective, safe, and accessible treatment, to fully establish the effectiveness of EA as a medication for DM, it is crucial to conduct further well-designed studies.