Mojzis J, Varinska L, Mojzisova G, Kostova I, Mirossay L
Department of Pharmacology, Faculty of Medicine, P.J. Safarik University, Trieda SNP 1, 04011 Kosice, Slovak Republic.
Pharmacol Res. 2008 Apr;57(4):259-65. doi: 10.1016/j.phrs.2008.02.005. Epub 2008 Feb 23.
Angiogenesis, the development of new blood vessels from the existing vasculature, is essential in normal developmental processes. Uncontrolled angiogenesis is a major contributor to a number of disease states such as inflammatory disorders, obesity, asthma, diabetes, cirrhosis, multiple sclerosis, endometriosis, AIDS, bacterial infections and autoimmune disease. It is also considered a key step in tumour growth, invasion, and metastasis. Angiogenesis is required for proper nourishment and removal of metabolic wastes from tumour sites. Therefore, modulation of angiogenesis is considered as therapeutic strategies of great importance for human health. Numerous bioactive plant compounds are recently tested for their antiangiogenic potential. Among the most frequently studied are polyphenols present in fruits and vegetables. Plant polyphenols inhibit angiogenesis and metastasis through regulation of multiple signalling pathways. Specifically, flavonoids and chalcones regulate expression of VEGF, matrix metalloproteinases (MMPs), EGFR and inhibit NFkappaB, PI3-K/Akt, ERK1/2 signalling pathways, thereby causing strong antiangiogenic effects. This review focuses on the antiangiogenic properties of flavonoids and chalcones and examines underlying mechanisms.
血管生成,即从现有脉管系统发育出新的血管,在正常发育过程中至关重要。不受控制的血管生成是导致多种疾病状态的主要因素,如炎症性疾病、肥胖症、哮喘、糖尿病、肝硬化、多发性硬化症、子宫内膜异位症、艾滋病、细菌感染和自身免疫性疾病。它也被认为是肿瘤生长、侵袭和转移的关键步骤。血管生成是肿瘤部位获得适当营养和清除代谢废物所必需的。因此,调节血管生成被视为对人类健康极为重要的治疗策略。最近对众多生物活性植物化合物的抗血管生成潜力进行了测试。其中研究最频繁的是水果和蔬菜中存在的多酚。植物多酚通过调节多种信号通路来抑制血管生成和转移。具体而言,黄酮类化合物和查耳酮调节血管内皮生长因子(VEGF)、基质金属蛋白酶(MMPs)、表皮生长因子受体(EGFR)的表达,并抑制核因子κB(NFκB)、磷脂酰肌醇-3激酶/蛋白激酶B(PI3-K/Akt)、细胞外信号调节激酶1/2(ERK1/2)信号通路,从而产生强大的抗血管生成作用。本综述重点关注黄酮类化合物和查耳酮的抗血管生成特性,并探讨其潜在机制。