Molecular Mechanisms of Epigallocatechin-3-Gallate for Prevention of Chronic Kidney Disease and Renal Fibrosis: Preclinical Evidence

Abstract

Chronic kidney disease (CKD) is a common public health problem worldwide characterized by gradual decline of renal function over months/years accompanied by renal fibrosis and failure in tissue wound healing after sustained injury. Patients with CKD frequently present with profound signs/symptoms that require medical treatment, mostly culminating in hemodialysis and renal transplantation. To prevent CKD more efficiently, there is an urgent need for better understanding of the pathogenic mechanisms and molecular pathways of the disease pathogenesis and progression, and for developing novel therapeutic targets. Recently, several lines of evidence have shown that epigallocatechin-3-gallate (EGCG), an abundant phytochemical polyphenol derived from Camellia sinensis, might be a promising bioactive compound for prevention of CKD development/progression. This review summarizes current knowledge of molecular mechanisms underlying renoprotective roles of EGCG in CKD based on available preclinical evidence (from both in vitro and in vivo animal studies), particularly its antioxidant property through preservation of mitochondrial function and activation of Nrf2 (nuclear factor erythroid 2-related factor 2)/HO-1 (heme oxygenase-1) signaling, anti-inflammatory activity, and protective effect against epithelial mesenchymal transition. Finally, future perspectives, challenges, and concerns regarding its clinical use in CKD and renal fibrosis are discussed.

Reactive Glia Inflammatory Signaling Pathways and Epilepsy

“…In order to prevent the overactivation of the TLRs, several strategies have been developed: (a) To reduce the IL-1β/IL-1R1 signaling pathway several authors have used anakinra (an antagonist of the IL-1R1 receptor) or anti-IL-1β monoclonal antibodies (reviewed in [10,24]); VX765 (an inhibitor of caspase 1, although its use has been dismissed because of its hepatic toxicity [16]); minocycline [25], or natural products such as epigallocatechin gallate (EGCG) or punicalagin ( [26,27], reviewed in [28]), although caution should be taken when the possible utility of these compounds is considered, as, at least in the case of EGCG, it is regarded a pan-assay interfering compound [29]. In all these cases, the administration of any of these compounds decreases the appearance of seizures, at least in animal models of epilepsy (reviewed in [10,24]) ( Table 1) (Figure 1, names in red).…”

The Regulation of Host Intestinal Microbiota by Polyphenols in the Development and Prevention of Chronic Kidney Disease

“…This research has shown that EGCG treatment can improve renal function can be and histopathology in kidney function-impaired mice (116). The treatment also regenerated Nrf2 and its downstream products, including a catalytic subset of glutamate-cysteine ligase, a subunit modification of glutamate-cysteine ligase, and glutathione peroxidase (GPx) (116). Funamoto et al also reported that EGCG may have a renoprotective effect after cardiopulmonary bypass in diabetic rats (117).…”

“…In a mouse model of crescentic glomerulonephritis, the therapeutic potential of EGCG was also demonstrated. This research has shown that EGCG treatment can improve renal function can be and histopathology in kidney function-impaired mice (116). The treatment also regenerated Nrf2 and its downstream products, including a catalytic subset of glutamate-cysteine ligase, a subunit modification of glutamate-cysteine ligase, and glutathione peroxidase (GPx) (116).…”

Heme-Oxygenase and Kidney Transplantation: A Potential for Target Therapy?

“…In these conditions of severe injury, together with an overload of reactive oxygen species (ROS), these cytochromes spill from the mitochondrion’s inner membrane and may overwhelm the capacity of HO-1 to convert the cytochromes to more inert compounds [ 18 ]. Moreover, ROS may disrupt the intracellular metabolic structure and also the proximal tubular cell super structure of the kidney which is, together with the heart, a mitochondria rich organ relative to tissue mass [ 23 ], and this could have a role in the progression of kidney disease [ 24 , 25 ]. Adenosine triphosphate depletion and loss of the mitochondrial membrane potential required for oxidative phosphorylation, renders the process irreversible with cellular necrosis [ 19 ].…”

“…The epigallocatechin-3-gallate (EGCG), an abundant phytochemical polyphenol derived from Camellia sinensis, may promote the preservation of mitochondrial function through the activation of nuclear factor erythroid 2-related factor 2 (Nrf2)/HO-1 signaling, and this results in upregulation of antioxidant or detoxifying enzymes [ 23 ], finally preserving the renal function [ 26 ].…”