Small molecules from natural products targeting the Wnt/β-catenin pathway as a therapeutic strategy

The Wnt/beta-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/beta-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/beta-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/beta-catenin pathway, especially for porcupine, the receptors of Wnt ligands, beta-catenin and beta-catenin-dependent proteins. Additionally, a series of natural small molecules have shown good therapeutic effects against mutations of the Wnt/beta-catenin pathway, which may dramatically facilitate the development of natural products in Wnt/beta-catenin pathway intervention.