Molecular Mechanistic Pathways Targeted by Natural Antioxidants in the Prevention and Treatment of Chronic Kidney Disease

Chronic kidney disease (CKD) is the progressive loss of renal function and the leading cause of end-stage renal disease (ESRD). Despite optimal therapy, many patients progress to ESRD and require dialysis or transplantation. The pathogenesis of CKD involves inflammation, kidney fibrosis, and blunted renal cellular antioxidant capacity. In this review, we have focused on in vitro and in vivo experimental and clinical studies undertaken to investigate the mechanistic pathways by which these compounds exert their effects against the progression of CKD, particularly diabetic nephropathy and kidney fibrosis. The accumulated and collected data from preclinical and clinical studies revealed that these plants/bioactive compounds could activate autophagy, increase mitochondrial bioenergetics and prevent mitochondrial dysfunction, act as modulators of signaling pathways involved in inflammation, oxidative stress, and renal fibrosis. The main pathways targeted by these compounds include the canonical nuclear factor kappa B (NF-κB), canonical transforming growth factor-beta (TGF-β), autophagy, and Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid factor 2-related factor 2 (Nrf2)/antioxidant response element (ARE). This review presented an updated overview of the potential benefits of these antioxidants and new strategies to treat or reduce CKD progression, although the limitations related to the traditional formulation, lack of standardization, side effects, and safety.