Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Curr Top Med Chem. 2012;12(19):2103-13. doi: 10.2174/156802612804910241.
Maternal Wnt/β-Catenin signaling is essential to establish dorsal-specific gene expression required for axial patterning in Xenopus. Deregulation of this pathway causes axis phenotypes in frog embryos. In adult life, mutations in the Wnt pathway components are associated with many diseases, such as polyposis coli; osteoporosis-pseudoglioma syndrome (OPPG); skeletal dysplasia; neural tube defects, cancer and many others. Thus, a better understanding of Wnt/β-catenin signaling will have great and significant impact on Biology and Medicine. In this aspect, natural compounds are potential targets as novel molecules that could modulate the Wnt pathway. For instance, flavonoids are a large group of natural compounds found in plants that modulate important cellular and molecular mechanisms related to diseases, but the specific in vivo mechanism of action of most flavonoids remain unknown. In this way, Xenopus embryos may provide an efficient model, since it is frequently used to test and identify the role of molecules that affect Wnt/β-catenin signaling. Here, we describe a combination of approaches to outline and characterize the role of two flavonoids, quercetin and rutin, on Wnt/β-catenin signaling, using Xenopus embryos as an experimental model. Our data support that quercetin is potential in vivo modulator of canonical Wnt signaling and that this effect might depend on the structure of this molecule, as we did not observe any effect with rutin treatment, a flavonol structurally-related to quercetin. This model is useful to analyze effects of quercetin and other flavonoids in vivo and to provide further understanding of how natural compounds can modulate signaling pathways, using Xenopus embryos as a fast and efficient reading of in vivo effects of those compounds.
母体 Wnt/β-连环蛋白信号对于建立非洲爪蟾轴向模式形成所必需的背侧特异性基因表达至关重要。该途径的失调会导致青蛙胚胎出现轴突表型。在成年期，Wnt 途径成分的突变与许多疾病有关，如结肠息肉；骨质疏松-假性脑肿瘤综合征（OPPG）；骨骼发育不良；神经管缺陷、癌症等。因此，更好地理解 Wnt/β-连环蛋白信号将对生物学和医学产生重大而深远的影响。在这方面，天然化合物是作为潜在的新分子的靶点，这些新分子可以调节 Wnt 途径。例如，类黄酮是植物中发现的一大类天然化合物，可调节与疾病相关的重要细胞和分子机制，但大多数类黄酮的具体体内作用机制仍不清楚。在这种情况下，非洲爪蟾胚胎可能提供一个有效的模型，因为它经常被用于测试和识别影响 Wnt/β-连环蛋白信号的分子的作用。在这里，我们描述了一种结合使用的方法，以概述和表征两种类黄酮，槲皮素和芦丁，在 Wnt/β-连环蛋白信号中的作用，使用非洲爪蟾胚胎作为实验模型。我们的数据支持槲皮素是经典 Wnt 信号的潜在体内调节剂，并且这种作用可能取决于该分子的结构，因为我们在用芦丁处理时没有观察到任何作用，芦丁是一种与槲皮素结构相关的类黄酮。该模型可用于分析槲皮素和其他类黄酮在体内的作用，并进一步了解天然化合物如何调节信号通路，使用非洲爪蟾胚胎作为快速有效的体内化合物作用的阅读方法。
