Diabetic nephropathy: Pathophysiology and potential therapeutic role of plant extracts

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This review aims to explore the molecular mechanisms underlying diabetic nephropathy (DN), with a particular focus on the role of oxidative stress. Additionally, it evaluates the therapeutic potential of plant-based extracts rich in bioactive compounds for the management of diabetes and its associated renal complications. Oxidative stress is identified as a key contributor to DN pathogenesis. Several major pathways are involved, including hypoxia-inducible factor-1 (HIF-1), transforming growth factor-beta (TGF-β), mitochondrial dysfunction, renin-angiotensin-aldosterone system (RAAS) activation, and endothelial nitric oxide synthase (eNOS) uncoupling. These mechanisms collectively lead to podocyte injury, tubular damage, extracellular matrix accumulation, disrupted renal hemodynamics, and glomerular hyperfiltration. Plant-derived compounds have shown potential in modulating these pathways, thereby offering renal protective effects. Plant-based remedies enriched with bioactive compounds represent promising adjunct therapies for managing diabetes and its renal complications. Their integration into conventional treatment regimens may provide a holistic approach to glycemic control and reduction of oxidative stress-induced kidney damage. This review underscores the importance of multifaceted therapeutic strategies targeting both metabolic dysregulation and oxidative stress to effectively prevent and manage diabetic nephropathy. • Oxidative stress is a key driver of nephropathy, leading to kidney damage through reactive oxygen species (ROS), alters hypoxia-inducible factor-1 (HIF-1) signaling, inflammation, podocyte dysfunction and extracellular matrix deposition. • Additionally, metabolic dysregulation, renin-angiotensin-aldosterone system (RAAS) activation, and endothelial nitric oxide synthase (eNOS) uncoupling contribute to DN progression. • The roles of cyclooxygenase and polyol pathways in renal hemodynamics, glycogen metabolism, and glomerular hyperfiltration • Current treatments have limitations, including side effects and incomplete protection against oxidative damage, necessitating alternative approaches. • Medicinal plants offer nephroprotective benefits due to their antioxidant, anti-inflammatory and anti-fibrotic properties.