Abstract
The Wnt/β-catenin signaling pathway is an evolutionarily conserved developmental signaling event that plays a critical role in regulating tissue development and maintaining homeostasis, the dysregulation of which contributes to various diseases. Natural products have been widely recognized as a treasure trove of novel drug discovery for millennia, and many clinical drugs are derived from natural small molecules. Mounting evidence has demonstrated that many natural small molecules could inhibit the Wnt/β-catenin pathway, while the efficacy of natural products remains to be determined. Therefore, this paper primarily reviews the targeting mechanism of natural small molecules for aberrant Wnt/β-catenin pathway that is intimately implicated in the pathogenesis of myriad diseases, such as cancers, renal diseases, neurodegenerative diseases and bone disorders. In addition, this review also highlights some natural products that have the potential to halt Wnt/β-catenin pathway, especially for porcupine, the receptors of Wnt ligands, β-catenin and β-catenin-dependent proteins. Additionally, a series of natural small molecules have shown good therapeutic effects against mutations of the Wnt/β-catenin pathway, which may dramatically facilitate the development of natural products in Wnt/β-catenin pathway intervention.
Highlights
Kidney diseases remain major health problems with a high prevalence around the world and a variety of pathophysiological processes are implicated in the progression [1,2,3]
We only briefly emphasize the recent advances in mediators of reactive oxygen species (ROS) generation that were closely associated with the regulation of kidney with aging and pathological conditions for the sake of brevity, including nicotinamide adenine dinucleotide phosphate oxidase (NOX), transforming growth factor-β (TGF-β), reninangiotensin system (RAS), nuclear factor-erythroid 2 related factor 2 (Nrf2), peroxisome proliferator-activated γ receptor (PPARγ), advanced glycation endproducts (AGEs) as well as microRNAs and vitagenes (Fig. 1)
Myriad studies highlighted that oxidative stress was a major etiology of diabetic nephropathy [4], and AGE-receptor for AGEs (RAGE) signaling pathway played crucial roles in the pathogenesis via exacerbating ROS generation [91], which had been recognized as one of the five cellular and molecular mechanisms of redox signaling in diabetic complications [4]
Summary
Kidney diseases remain major health problems with a high prevalence around the world and a variety of pathophysiological processes are implicated in the progression [1,2,3]. Oxidative stress is a pathological condition that reactive oxygen species (ROS) generation far exceeds the scavenging capacity of anti-oxidant defense systems, which plays a pivotal role in the pathogenesis of myriad renal disorders [4,5,6]. We only briefly emphasize the recent advances in mediators of ROS generation that were closely associated with the regulation of kidney with aging and pathological conditions for the sake of brevity, including nicotinamide adenine dinucleotide phosphate oxidase (NOX), transforming growth factor-β (TGF-β), reninangiotensin system (RAS), nuclear factor-erythroid 2 related factor 2 (Nrf2), peroxisome proliferator-activated γ receptor (PPARγ), advanced glycation endproducts (AGEs) as well as microRNAs and vitagenes (Fig. 1). ROS is of paramount significance to disease progression and a thorough understanding of these mediators will pave the way to the booming development of therapies against kidney diseases since they play vital roles in redox signaling. Oxidative stress associated novel mediators in aging kidney and renal diseases
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