通过体外、体内和计算机模拟研究，探讨恩贝林和维兰金对血管生成和一氧化氮合酶（NOS）的抑制作用。

Inhibition of Angiogenesis and Nitric Oxide Synthase (NOS), by Embelin & Vilangin Using in vitro, in vivo & in Silico Studies.

作者信息

Narayanaswamy Radhakrishnan, Shymatak Majumder, Chatterjee Suvro, Wai Lam Kok, Arumugam Gnanamani

机构信息

Microbiology Division, Central Leather Research Institute (CLRI), Chennai, India. ; Laboratory of Natural Products, Institute of Bioscience (IBS), Universiti Putra Malaysia (UPM), Serdang, Selangor, Malaysia.

Vascular Biology Laboratory, AU-KBC Research Centre, Anna University, Chennai, India.

出版信息

Adv Pharm Bull. 2014 Dec;4(Suppl 2):543-8. doi: 10.5681/apb.2014.080. Epub 2014 Dec 31.

DOI:10.5681/apb.2014.080

PMID:25671187

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4312403/

Abstract

PURPOSE

In recent year's anti-angiogenesis agents have been recognized as effective drugs for the treatment of solid tumors, this prompted us to conduct the present study.

METHODS

The anti-angiogenic activity of dimeric form of embelin (vilangin) was evaluated using endothelial cell (in vitro) and chorioallantoic membrane (CAM) egg yolk angiogenesis model (in vivo) and in addition the docking behaviour of human nitric oxide synthases (NOS) with four different ligands was evaluated along with their putative binding sites using Discovery Studio Version 3.1 (in silico) compared with the parent compound (embelin).

RESULTS

Vilangin exhibits 50% cytotoxic at 92 ± 1 µg/ml concentration level with reference to ECV 304 endothelial cells. Both vilangin and embelin, showed inhibitory effects on wound healing, single cell migration, nitric oxide production, and endothelial ring formation at 0.1 and 1.0 µg/ml concentration level. Similarly, CAM assay also showed inhibitory effect of vilangin and embelin with respect their reduction in length, size and junctions of blood capillaries compared to untreated egg yolk. Docking studies and binding free energy calculations revealed that vilangin has maximum interaction energy (-74.6 kcal/mol) as compared to the other investigated ligands.

CONCLUSION

The results suggest that both vilangin and embelin attenuates angiogenesis in similar manner.

摘要

目的

近年来，抗血管生成药物已被公认为治疗实体瘤的有效药物，这促使我们开展本研究。

方法

使用内皮细胞（体外）和绒毛尿囊膜（CAM）蛋黄血管生成模型（体内）评估紫铆因二聚体形式（vilangin）的抗血管生成活性，此外，使用Discovery Studio 3.1版本（计算机模拟）评估人一氧化氮合酶（NOS）与四种不同配体的对接行为及其假定的结合位点，并与母体化合物（紫铆因）进行比较。

结果

相对于ECV 304内皮细胞，vilangin在浓度为92±1μg/ml时表现出50%的细胞毒性。vilangin和紫铆因在浓度为0.1和1.0μg/ml时，均对伤口愈合、单细胞迁移、一氧化氮生成和内皮环形成有抑制作用。同样，CAM试验也显示，与未处理的蛋黄相比，vilangin和紫铆因对毛细血管的长度、大小和连接有抑制作用。对接研究和结合自由能计算表明，与其他研究的配体相比，vilangin具有最大的相互作用能（-74.6 kcal/mol）。