The Graduate School, University of Santo Tomas, Manila 1015, Philippines.
Department of Physical Sciences and Mathematics, College of Arts and Sciences, University of the Philippines Manila, Manila, Philippines.
Drug Des Devel Ther. 2020 Nov 25;14:5189-5204. doi: 10.2147/DDDT.S271952. eCollection 2020.
Cancer is considered as one of the deadliest human diseases today. Angiogenesis, the propagation of new blood vessels from pre-existing vasculature, is a critical step in the progression of cancer as it is essential in the growth and metastasis of tumors. Hence, suppression of angiogenesis is a promising approach in cancer therapy. Syringin, a phenylpropanoid glycoside with a molecular formula of CHO, has been found to exhibit chemopreventive effects. However, its anti-angiogenic activity and the underlying mechanism of action are still unknown.
In this work, in ovo chorioallantoic membrane (CAM) assay has been conducted to evaluate the effect of syringin on neovascularization. Additionally, reverse molecular docking studies have been performed in order to identify the probable enzyme targets in the angiogenesis pathway.
Treatment with syringin showed significant dose-dependent inhibition of blood vessel length and junctions in the CAM of duck eggs; the anti-angiogenic activity of syringin at 100 µM and 200 µM is comparable with 200 µM of the positive control celecoxib. The results of reverse docking studies indicate that syringin binds the strongest to dihydrofolate reductase (DHFR) and, to some extent, with transforming growth factor-beta receptor type 1 (TGF-βR1), vascular endothelial growth factor receptor 2 (VEGFR2), and matrix metalloproteinase-2 (MMP-2). Furthermore, ADMET models revealed that syringin potentially possesses excellent pharmacokinetic and toxicity profiles.
This study demonstrates the potential of syringin as an anti-angiogenic agent and elicits further investigations to establish its application in cancer suppression.
癌症被认为是当今最致命的人类疾病之一。血管生成，即新血管从预先存在的脉管系统中生长，是癌症进展的关键步骤，因为它对肿瘤的生长和转移至关重要。因此，抑制血管生成是癌症治疗的一种有前途的方法。丁香苷是一种苯丙素糖苷，分子式为 CHO，已被发现具有化学预防作用。然而，其抗血管生成活性及其作用机制尚不清楚。
在这项工作中，鸡胚尿囊膜（CAM）试验已被用于评估丁香苷对新血管生成的影响。此外，还进行了反向分子对接研究，以确定血管生成途径中的可能酶靶标。
丁香苷处理表现出明显的剂量依赖性抑制鸭胚 CAM 中的血管长度和连接处；丁香苷在 100 µM 和 200 µM 时的抗血管生成活性与 200 µM 的阳性对照塞来昔布相当。反向对接研究的结果表明，丁香苷与二氢叶酸还原酶（DHFR）结合最强，在某种程度上与转化生长因子-β受体 1（TGF-βR1）、血管内皮生长因子受体 2（VEGFR2）和基质金属蛋白酶 2（MMP-2）结合。此外，ADMET 模型表明，丁香苷可能具有良好的药代动力学和毒性特征。
本研究表明丁香苷具有作为抗血管生成剂的潜力，并引发了进一步的研究，以确定其在癌症抑制中的应用。
