How caffeic acid and its derivatives combat diabetes and its complications: A systematic review

Caffeic acid (CA) and its derivatives, caffeic acid phenyl ethyl amide (CAPA) and caffeic acid phenyl ester (CAPE), were shown to have anti-oxidant, anti-inflammatory, and anti-diabetic effects. Therefore, in this systematic review, a literature search was conducted from inception until June 2023 on major electronic databases (ISI Web of Science, MEDLINE/PubMed, Scopus, Cochrane Library, and Google Scholar) to find studies evaluating the impacts of CA and its common derivatives on diabetes and its complications in different cellular, animal, and clinical studies. CA and its derivatives therapy mitigated levels of blood glucose, oxidative stress markers, and inflammatory cytokines while increasing levels of anti-oxidative markers in different cellular and animal models of diabetes. Furthermore, they remarkably propagated insulin secretion and ameliorated insulin resistance. CA and its derivatives also revealed protective effects against diabetes complications, such as diabetic-induced hepatic damage, cardiomyopathy, endothelial dysfunction, retinopathy, cognitive deficit, nephropathy, and neuropathy.