Plant-Derived Flavonoids Ameliorate Diabetic Nephropathy: Molecular Mechanisms and Therapeutic Potential.

Abstract

Diabetic nephropathy (DN) is a major microvascular complication of diabetes mellitus and a leading cause of chronic kidney disease and end-stage renal disease. Although current therapeutic strategies can delay disease progression, they remain insufficient to reverse established renal injury. Plant-derived flavonoids, a class of natural polyphenolic compounds, have attracted increasing attention due to their diverse pharmacological properties. This structured narrative review summarizes the major molecular mechanisms underlying the protective effects of plant-derived flavonoids against DN. A comprehensive literature search was conducted in PubMed, Web of Science, and MEDLINE from database inception through December 25, 2025. A total of 251 relevant studies were included (54 in vitro only, 107 in vivo only, and 90 involving both). The evidence indicates that plant-derived flavonoids may exert renoprotective effects through diverse mechanisms, including the modulation of inflammation, oxidative stress, fibrosis, autophagy, apoptosis, ferroptosis, and microRNA (miRNA)-mediated regulatory pathways. Collectively, these flavonoids, such as kaempferol, quercetin, puerarin, and (-)-epigallocatechin-3-gallate (EGCG), demonstrate multi-target therapeutic potential against DN and may serve as promising adjunctive agents for disease management. However, the current evidence is predominantly derived from preclinical studies, and well-designed randomized controlled trials are required to further validate their efficacy and safety and to facilitate clinical translation.