Gene–pathway–organ perspective on quercetin in diabetic complications: A narrative review of preclinical evidence

Abstract: Diabetic complications involve multiple mechanisms, including metabolic disorders, oxidative stress, inflammation, fibrosis and apoptosis. Quercetin possesses multi-target regulatory potential, but relevant preclinical evidence remains scattered across different organs and signaling pathways. This narrative review aims to synthesize rodent evidence on quercetin-related genes, signaling pathways and organ protection in diabetic complications from a gene–pathway–organ perspective. Relevant rodent studies published from inception to June 2025 were searched in PubMed, EMBASE, Web of Science, Cochrane Library and Springer Link databases. Seventy-eight studies were included after screening. Due to significant heterogeneity among studies, a narrative approach was used for evidence synthesis. Quercetin mainly regulates pathways such as AMPK, PI3K/Akt, Nrf2/HO-1, NF-κB, TGF-β/Smad3, SIRT1 and NLRP3 and is involved in metabolic, cardiovascular, hepatic, renal, nervous, intestinal, wound-healing, reproductive and retinal systems. Evidence is strong in the metabolic-cardiovascular, hepatic and renal systems, moderate in the nervous and intestinal systems and limited in other systems. Current animal evidence suggests that quercetin may act as a multi-target regulator in the intervention of diabetic complications. This "gene-pathway-organ" framework can serve as a hypothesis-generating tool to identify key molecular hubs, compare the strength of evidence across different organs and guide subsequent mechanism validation and translational research.