Medicinal Plants and Phytochemicals used in Diabetic Nephropathy: A Comprehensive Review

Diabetic nephropathy (DN) is a major microvascular complication of diabetes mellitus and remains one of the leading causes of chronic kidney disease and end-stage renal disease worldwide. Although current therapeutic strategies, including glycemic control and renin–angiotensin–aldosterone system blockade, can slow disease progression, they do not adequately address the complex molecular mechanisms underlying DN pathogenesis and are often insufficient to halt progressive renal fibrosis and functional decline. Growing evidence suggests that medicinal plants and their bioactive phytochemicals exert multitarget effects by modulating oxidative stress, inflammation, fibrosis, and metabolic dysregulation. This review critically synthesises recent preclinical and clinical evidence on plant-derived interventions in DN, with particular emphasis on molecular signalling pathways, biomarker modulation, and translational relevance. Key medicinal plants, as well as reported phytochemicals, are evaluated for their nephroprotective effects. Mechanistically, these agents influence pivotal pathways, including Nrf2/Keap1-mediated antioxidant defence, NF-κB–driven inflammatory signalling, TGF-β/Smad-dependent fibrogenesis, and NLRP3 inflammasome activation. Clinical and meta-analytic data indicate that selected plant-based interventions may reduce proteinuria, improve estimated glomerular filtration rate (eGFR), and attenuate oxidative and inflammatory biomarkers, with generally favourable safety profiles when standardised formulations are used. However, significant challenges remain, including variability in herbal preparation standardisation, heterogeneity in study design, and limited high-quality randomised controlled trials. Future research should prioritise standardised botanical formulations, biomarker-guided clinical evaluation, and advanced omics-based approaches to clarify precise molecular targets and optimise therapeutic integration. Overall, medicinal plants represent promising adjunct strategies in the mechanism-oriented management of diabetic nephropathy.