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

Abstract

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.

Oridonin Attenuates Cisplatin-Induced Acute Kidney Injury via Inhibiting Oxidative Stress, Apoptosis, and Inflammation in Mice

“…Animal studies have shown that cisplatin nephrotoxicity is alleviated by administration of various antioxidants, such as coenzyme Q10 [ 26 ], vitamin C [ 27 ], vitamin E [ 28 ], resveratrol [ 29 ], and melatonin [ 30 ], suggesting that oxidative stress is also an important mechanism of cisplatin nephrotoxicity. Importantly, various natural compounds have antioxidative activity [ 31 , 32 ]. Antioxidative effect of oridonin has also been reported in several studies [ 8 , 9 ].…”

β-Elemene Attenuates Renal Fibrosis in the Unilateral Ureteral Obstruction Model by Inhibition of STAT3 and Smad3 Signaling via Suppressing MyD88 Expression

“…Chronic kidney disease (CKD) is one of the fastest-growing causes of death worldwide, with progressive loss of kidney function leading to end-stage renal disease (ESRD) [ 1 ]. Fibrosis is considered the ultimate common pathway leading to ESRD [ 2 ]. The pathogenesis of renal fibrosis is characterized by glomerulosclerosis, fibrosis of the tubular interstitium and blood vessels, and scar formation.…”

Applying a convolutional neural network as a statistical method to evaluate the correlation between diabetic retinopathy and diabetic nephropathy

“…In addition, almost 80% of patients with diabetes whose course of disease exceeds 10 years are diagnosed with DR, and their visual quality gradually decreases with time [11] . Similar to the pathogenesis of DR caused by diabetes, DN is also considered to be a microvascular disease caused by diabetes, and its most characteristic feature is the formation of diabetes glomerulosclerosis [12,13] . Moreover, approximately 25% of diabetic patients have renal complications, which have become the primary cause of end-stage renal disease (ESRD) in developed countries [14] .…”