Manandhar Suman, Kabekkodu Shama Prasada, Pai K Sreedhara Ranganath
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, India.
Department of Cell and Molecular Biology, School of Life Sciences, Manipal Academy of Higher Education, Manipal 576104, India.
Phytomedicine. 2020 May 23;76:153243. doi: 10.1016/j.phymed.2020.153243.
Wnt signaling pathway plays a major role during development like gastrulation, axis formation, organ development and organization of body plan development. Wnt signaling aberration has been linked with various disease conditions like osteoporosis, colon cancer, hair follicle tumor, Leukemia, and Alzheimer's disease. Phytochemicals like flavonoid, glycosides, polyphenols, have been reported to directly target the markers of Wnt signaling in different disease models.
The study deals in detail about the different phytochemical targeting key players of Wnt signaling pathway in diseases like Cancer, Osteoporosis, and Alzheimer's disease. We have focused on the Pharmacological basis of disease alleviation by phytochemical specifically targeting the Wnt signaling markers in this study.
The study focused on the published articles from the preclinical rodent and invitro cell line studies related to Wnt signaling and Phytochemicals related to Cancer, Alzheimer's and Osteoporosis. The electronic databases Scopus, Web of Science and Pubmed database were used for the systematic search of literatures from 2005 up to 2019 using keywords Canonical Wnt signaling pathway, Cancer, Alzheimer's disease, Osteoporosis, Phytochemicals. The focus was to identify the target specific modulation of Wnt signaling mediated by phytochemicals.
Approximately 30 phytochemicals of different class have been identified to modulate Wnt signaling pathway acting through Axin, β-catenin translocation, GSK-3β, AKT, Wif-1 in various experimental studies. The down regulation of Wnt signaling is observed in Cancer mostly colorectal cancer, breast cancer mediated through mutations in APC and Axin genes. Different class of Phytochemicals such as flavonoid, glycosides, polyphenol, alkaloids etc. have been found to target Wnt signaling markers and alleviate Cancer. Similarly, Up regulation of Wnt signaling has been reported in Osteoporosis and neurodegenerative disease like Alzheimer's disease.
This review highlights the possibility of the Phytochemicals to target Wnt markers and its potential to either activate or deactivate the Wnt signaling pathway. It also describes the challenges in proper targeting of Wnt signaling and the potential risk and consequences of either up regulation or down regulation of the signaling pathway. This article highlights the possibility of Wnt signaling pathway as a therapeutic option in different diseases.
Wnt信号通路在胚胎发育过程中发挥着重要作用，如原肠胚形成、轴形成、器官发育以及身体计划发育的组织构建。Wnt信号异常与多种疾病相关，如骨质疏松症、结肠癌、毛囊肿瘤、白血病和阿尔茨海默病。据报道，黄酮类、糖苷类、多酚类等植物化学物质在不同疾病模型中可直接作用于Wnt信号通路的标志物。
本研究详细探讨了不同植物化学物质在癌症、骨质疏松症和阿尔茨海默病等疾病中对Wnt信号通路关键分子的靶向作用。在本研究中，我们重点关注了植物化学物质通过特异性靶向Wnt信号标志物来缓解疾病的药理学基础。
本研究聚焦于已发表的与Wnt信号以及与癌症、阿尔茨海默病和骨质疏松症相关的植物化学物质的临床前啮齿动物和体外细胞系研究文章。使用电子数据库Scopus、科学网和PubMed数据库，通过关键词“经典Wnt信号通路”、“癌症”、“阿尔茨海默病”、“骨质疏松症”、“植物化学物质”，对2005年至2019年的文献进行系统检索。重点是确定植物化学物质介导的Wnt信号的靶向特异性调节。
在各种实验研究中，已鉴定出约30种不同类别的植物化学物质可通过Axin、β-连环蛋白易位、糖原合成酶激酶-3β（GSK-3β）、蛋白激酶B（AKT）、Wnt抑制因子-1（Wif-1）调节Wnt信号通路。在癌症中，尤其是结直肠癌、乳腺癌中，通过腺瘤性息肉病（APC）和Axin基因的突变介导，观察到Wnt信号的下调。已发现不同类别的植物化学物质，如黄酮类、糖苷类、多酚类、生物碱等，可靶向Wnt信号标志物并缓解癌症。同样，在骨质疏松症和神经退行性疾病如阿尔茨海默病中，已报道Wnt信号上调。
本综述强调了植物化学物质靶向Wnt标志物的可能性及其激活或失活Wnt信号通路的潜力。它还描述了Wnt信号正确靶向的挑战以及信号通路上调或下调的潜在风险和后果。本文强调了Wnt信号通路作为不同疾病治疗选择的可能性。
