Department of Zoology, Molecular Oncology Laboratory, University of Delhi (North Campus), Delhi, 110007, India.
Neuropharmacology and Drug Delivery Laboratory, Daulat Ram College, University of Delhi, Delhi, India.
Curr Top Med Chem. 2024;24(4):259-300. doi: 10.2174/0115680266264349231016094456.
Angiogenesis, the formation of new blood vessels from a pre-existing vascular network, is an important hallmark of several pathological conditions, such as tumor growth and metastasis, proliferative retinopathies, including proliferative diabetic retinopathy and retinopathy of prematurity, age-related macular degeneration, rheumatoid arthritis, psoriasis, and endometriosis. Putting a halt to pathology-driven angiogenesis is considered an important therapeutic strategy to slow down or reduce the severity of pathological disorders. Considering the attrition rate of synthetic antiangiogenic compounds from the lab to reaching the market due to severe side effects, several compounds of natural origin are being explored for their antiangiogenic properties. Employing pre-clinical models for the evaluation of novel antiangiogenic compounds is a promising strategy for rapid screening of antiangiogenic compounds. These studies use a spectrum of angiogenic model systems that include HUVEC two-dimensional culture, nude mice, chick chorioallantoic membrane, transgenic zebrafish, and dorsal aorta from rats and chicks, depending upon available resources. The present article emphasizes the antiangiogenic activity of the phytochemicals shown to exhibit antiangiogenic behavior in these well-defined existing angiogenic models and highlights key molecular targets. Different models help to get a quick understanding of the efficacy and therapeutics mechanism of emerging lead molecules. The inherent variability in assays and corresponding different phytochemicals tested in each study prevent their immediate utilization in clinical studies. This review will discuss phytochemicals discovered using suitable preclinical antiangiogenic models, along with a special mention of leads that have entered clinical evaluation.
血管生成，即从预先存在的血管网络中形成新的血管，是几种病理状况的重要标志，如肿瘤生长和转移、增生性视网膜病变，包括增生性糖尿病视网膜病变和早产儿视网膜病变、年龄相关性黄斑变性、类风湿性关节炎、银屑病和子宫内膜异位症。阻止病理驱动的血管生成被认为是一种重要的治疗策略，可以减缓或减轻病理紊乱的严重程度。由于合成抗血管生成化合物的严重副作用导致其从实验室到进入市场的淘汰率很高，因此正在探索几种天然来源的化合物的抗血管生成特性。在临床前模型中评估新型抗血管生成化合物是快速筛选抗血管生成化合物的有前途的策略。这些研究使用一系列血管生成模型系统，包括 HUVEC 二维培养、裸鼠、鸡胚绒毛尿囊膜、转基因斑马鱼，以及大鼠和小鸡的背主动脉，具体取决于可用资源。本文强调了在这些已明确的现有血管生成模型中表现出抗血管生成行为的植物化学物质的抗血管生成活性，并突出了关键的分子靶点。不同的模型有助于快速了解新兴先导分子的疗效和治疗机制。由于每种研究中使用的测定方法和相应的不同植物化学物质存在固有差异，因此它们不能立即在临床研究中使用。本综述将讨论使用合适的临床前抗血管生成模型发现的植物化学物质，特别提到已进入临床评估的先导化合物。
