PHYTOCHEMICAL CONSTITUENTS WITH NEPHROPROTECTIVE POTENTIAL: MECHANISMS OF ACTION AND THERAPEUTIC APPLICATIONS

Abstract

Kidney diseases constitute a major global health challenge, encompassing acute kidney injury, chronic kidney disease, diabetic nephropathy, and drug- or ischemia-induced renal damage. These conditions share common pathogenic mechanisms, including oxidative stress, inflammation, mitochondrial dysfunction, dysregulated cell death, and progressive fibrotic remodeling, which ultimately lead to irreversible loss of renal function. Current therapeutic strategies primarily focus on managing underlying causes and slowing disease progression, yet they often fail to directly protect renal cells and may themselves contribute to nephrotoxicity. In this context, phytochemicals have gained increasing attention as promising nephroprotective agents due to their multi-target biological activities and generally favorable safety profiles. This review systematically summarizes current evidence on phytochemical constituents with nephroprotective potential, emphasizing their classification, molecular mechanisms of action, and therapeutic relevance across diverse renal disorders. Experimental findings from in vitro renal cell models elucidate key cellular and molecular pathways modulated by phytochemicals, while in vivo animal studies validate their efficacy in preserving renal function and architecture under pathological conditions. Particular focus is given to antioxidant, anti-inflammatory, anti-apoptotic, and anti-fibrotic mechanisms underlying phytochemical-mediated renal protection. The review further discusses translational aspects, including adjunctive and synergistic applications with conventional therapies, as well as challenges related to formulation, bioavailability, safety, and standardization. Overall, the accumulated evidence highlights phytochemicals as valuable candidates for integrative nephroprotective strategies and underscores the need for well-designed clinical studies to facilitate their translation into evidence-based renal therapeutics.