Regulation of autophagy by natural polyphenols in the treatment of diabetic kidney disease: therapeutic potential and mechanism

Abstract

Diabetic kidney disease (DKD) is a major microvascular complication of diabetes and a leading cause of end-stage renal disease worldwide. Autophagy plays an important role in maintaining cellular homeostasis in renal physiology. In DKD, the accumulation of advanced glycation end products induces decreased renal autophagy-related protein expression and transcription factor EB (TFEB) nuclear transfer, leading to impaired autophagy and lysosomal function and blockage of autophagic flux. This accelerates renal resident cell injury and apoptosis, mediates macrophage infiltration and phenotypic changes, ultimately leading to aggravated proteinuria and fibrosis in DKD. Natural polyphenols show promise in treating DKD by regulating autophagy and promoting nuclear transfer of TFEB and lysosomal repair. This review summarizes the characteristics of autophagy in DKD, and the potential application and mechanisms of some known natural polyphenols as autophagy regulators in DKD, with the goal of contributing to a deeper understanding of natural polyphenol mechanisms in the treatment of DKD and promoting the development of their applications. Finally, we point out the limitations of polyphenols in current DKD research and provide an outlook for their future research.

Targeting autophagy with natural products as a potential therapeutic approach for diabetic microangiopathy

“…In recent decades, natural products (NPs) sourced from plants, animals, and microorganisms have attracted increased attention given their multifaceted components, ability to target multiple pathways, accessibility, and low toxicity levels ( Newman and Cragg, 2016 ; Newman and Cragg, 2020 ). Recent studies have increasingly demonstrated the therapeutic potential of NPs in DR, DKD, DC, and DPN by modulating autophagy ( Yao et al, 2018 ; Zhou P. et al, 2019 ; Yin et al, 2021 ; Liu P. et al, 2023 ; Liu T. et al, 2023 ). This article reviews recent research on autophagy and DMC, exploring the role and mechanism of NPs in enhancing DMC efficacy by regulating autophagy.…”