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

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 because of their diverse pharmacologic 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 25 December 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-mediated regulatory pathways. Collectively, these flavonoids, such as kaempferol, quercetin, puerarin, and (-)-epigallocatechin-3-gallate, demonstrate multitarget 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. The Author(s) This is an open access article under the CC BY license. http://creativecommons.org/licenses/by/4.0/