Abstract
The global burden of chronic kidney disease (CKD) intertwined with cardiovascular disease has become a major health problem. Oxidative stress (OS) plays an important role in the pathophysiology of CKD. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant responsive element (ARE) antioxidant system plays a critical role in kidney protection by regulating antioxidants during OS. Heme oxygenase-1 (HO-1), one of the targets of Nrf2-ARE, plays an important role in regulating OS and is protective in a variety of human and animal models of kidney disease. Thus, activation of Nrf2-HO-1 signaling may offer a potential approach to the design of novel therapeutic agents for kidney diseases. In this review, we have discussed the association between OS and the pathogenesis of CKD. We propose Nrf2-HO-1 signaling-mediated cell survival systems be explored as pharmacological targets for the treatment of CKD and have reviewed the literature on the beneficial effects of small molecule natural products that may provide protection against CKD.
Highlights
The incidence and prevalence of chronic kidney disease (CKD) patients is increasing worldwide
Cells have their own antioxidant defense system to tackle the effects of oxidative stress (OS), and nuclear factor erythroid 2-related factor 2 (Nrf2)-Heme oxygenase-1 (HO-1) signaling is an important antioxidant defense system against various diseases, including CKD
The expression of Nrf2 and HO-1 were set as outcome measures (Table 3), Nrf2 activates HO-1 under OS in many preclinical settings of CKD
Summary
The incidence and prevalence of chronic kidney disease (CKD) patients is increasing worldwide. Promoting the endogenous antioxidants defense system may become an important strategy in inhibiting OS-mediated cellular damage in CKD. The literature on protective effects of antioxidant natural products against CKD has been reported [18,19,20]. Studies review that augmentation of Nrf activity prevents the progression of acute kidney injury (AKI) to CKD transition [21,22]. Natural bioactive compounds and their sources have been demonstrated to have kidney protective potential by activating Nrf in experimental CKD models [23,24]. In a recent review on clinical studies, bardoxolone methyl (CDDO-me), a semi-synthetic triterpenoid activating the Nrf pathway, has been reported as an effective therapeutic for diabetic kidney disease (DKD), it has limitations in that it increases the risk of heart failure [25]. We have discussed the recent literature on its protective effects on the kidney and the underlying pharmacological mechanisms of bioactive phytochemicals that activate Nrf2-HO-1-mediated kidney protective actions
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