Natural products modulate renal metabolic reprogramming in diabetic kidney disease
Abstract Diabetic kidney disease (DKD) is a major cause of end-stage renal disease worldwide. Its pathogenesis is highly complex and involves dysfunction across multiple renal cell types and metabolic pathways, thereby underscoring the urgent need for novel therapeutic strategies. In recent years, renal metabolic reprogramming has been increasingly recognized as a central driver of DKD progression. This review systematically examines the mechanisms of metabolic reprogramming in different renal cell types and highlights their contribution to renal injury. Particular emphasis is placed on the ability of natural products (including glycosides, terpenoids, flavonoids, alkaloids, and polysaccharides) to confer renal protection by modulating key regulatory nodes of metabolic reprogramming. Through these mechanisms, natural products enhance mitochondrial function, suppress aberrant glycolysis, and improve hypoxia-related responses. Collectively, these findings not only underscore the therapeutic potential of natural products in targeting renal metabolic reprogramming but also provide a theoretical foundation and potential molecular targets for the development of novel DKD treatment strategies.