Abstract
Kidney diseases, including acute kidney injury and chronic kidney disease, represent a growing global health burden associated with nephrotoxic drugs, environmental toxins, metabolic disorders, and aging. Nephrotoxicity arises through complex and interconnected mechanisms, including oxidative stress, inflammation, mitochondrial dysfunction, apoptosis, tubular epithelial cell injury, fibrosis, and altered glomerular hemodynamics, ultimately leading to progressive renal dysfunction. The limited sensitivity of conventional biomarkers for early diagnosis and the lack of effective targeted therapies highlights the need for novel preventive and therapeutic strategies. In recent years, phytomedicines have attracted considerable attention owing to their multitargeted pharmacological actions and favorable safety profiles. This comprehensive review summarizes the molecular mechanisms underlying nephrotoxicity, major nephrotoxic agents, and recent advances in nephroprotective medicinal plants, herbal formulations, and phytocompounds. Bioactive constituents, including flavonoids, polyphenols, alkaloids, terpenoids, saponins, and phenolic acids, exert renoprotective effects by attenuating oxidative stress, suppressing inflammatory signaling pathways such as NF-κB, regulating apoptosis and autophagy, preserving mitochondrial function, and activating cytoprotective pathways, particularly Nrf2/HO-1. Experimental studies consistently demonstrate that phytocompounds such as curcumin, dioscin, ferulic acid, thymoquinone, quercetin, and resveratrol improve renal biochemical, molecular, and histopathological outcomes across diverse models of nephrotoxicity. The review also critically discusses available clinical evidence, pharmacokinetic limitations, issues of standardization and quality control, safety considerations, and emerging strategies to enhance clinical translation. Collectively, evidences highlight phytomedicines as promising candidates for preventing and managing nephrotoxicity and kidney diseases while providing a scientific framework for future mechanistic studies, biomarker-guided investigations, and well-designed clinical trials to facilitate the development of effective renoprotective therapeutics.