Mathi Pardhasaradhi, Veeramachaneni Ganesh Kumar, Raj K Kranthi, Talluri Venkateswara Rao, Bokka Venkata Raman, Botlagunta Mahendran
Biomedical Research Laboratory, Department of Biotechnology, KLEF University (Koneru Lakshmaiah Educational Foundation), Green fields; Vaddeswaram, Guntur (Dist), 522502, Andhra Pradesh, India.
Upstream Process Development Team, Lupin Limited, Biotechnology R&D, 1156, Ghotawade Village, Mulshi Taluka, Pune-411042, India.
J Mol Model. 2016 Oct;22(10):247. doi: 10.1007/s00894-016-3102-1. Epub 2016 Sep 28.
Sophora interrupta Bedd, (Fabaceae) is used in Indian folk medicine to treat cancer. Angiogenesis is one of the crucial characteristics of cancer metastasis and is regulated by vascular endothelial growth factor (VEGF). In this study, we examined the antiangiogenic properties of the root ethyl acetate extract of Sophora interrupta by various methods. In vitro antioxidant activity (100-600 μg/ml) of S. interrupta ethyl acetate (SEA) extract was evaluated by DPPH and ABTS, anti-inflammatory activity (50, 100 and 150 μg/ml) by estimating nitric oxide (NO) levels, anti-angiogenic activity (200 and 500 μg/ml) was validated by chorio allantoic membrane (CAM) assay and in silico molecular dynamic (MD) simulations analyses (25 ns) were performed to identify the anti-angiogenic compounds extracted from root extract. The antioxidative activity of SEA extract at IC (200 ± 0.6 μg/mL) is equal to that of ascorbic acid at IC (50 ± 0.6 μg/mL), and the anti-inflammatory activity of SEA extract at IC (150 ± 0.2 μg/mL) was inhibited significantly by nitric oxide (NO) production. The SEA extract significantly reduced the sprouting of new blood vessels at ID 500 ± 0.13 μg/mL in the CAM assay. Gas chromatography-mass spectrometry analysis of the SEA extract detected 34 secondary metabolites, of which 6a,12a-dihydro-6H-(1,3)dioxolo(5,6)benzofuro(3,2-c)chromen-3-ol (maackiain) and funiculosin formed strong hydrogen bond interactions with Lys 920, Thr 916 and Cys 919 (2H), as well as Glu 917 of VEGFR2, and these interactions were similar to those of the anti-angiogenic compound axitinib. Significant findings in all the assays performed indicate that SEA extract has potential anti-angiogenic compounds that may interfere with VEGF-induced cancer malignancy.
间断槐（豆科）在印度民间医学中用于治疗癌症。血管生成是癌症转移的关键特征之一，受血管内皮生长因子（VEGF）调控。在本研究中，我们通过多种方法检测了间断槐根乙酸乙酯提取物的抗血管生成特性。采用DPPH和ABTS法评估间断槐乙酸乙酯（SEA）提取物的体外抗氧化活性（100 - 600μg/ml），通过测定一氧化氮（NO）水平评估抗炎活性（50、100和150μg/ml），采用鸡胚绒毛尿囊膜（CAM）试验验证抗血管生成活性（200和500μg/ml），并进行计算机模拟分子动力学（MD）模拟分析（25 ns）以鉴定从根提取物中提取的抗血管生成化合物。SEA提取物在IC（200±0.6μg/mL）时的抗氧化活性与抗坏血酸在IC（50±0.6μg/mL）时相当，SEA提取物在IC（150±0.2μg/mL）时的抗炎活性因一氧化氮（NO）生成而受到显著抑制。在CAM试验中，SEA提取物在ID 500±0.13μg/mL时显著减少了新血管的萌发。对SEA提取物进行气相色谱 - 质谱分析检测到34种次生代谢产物，其中6a,12a - 二氢 - 6H - (1,3)二氧杂环戊烯并(5,6)苯并呋喃并(3,2 - c)色烯 - 3 - 醇（紫铆因）和绳状菌素与VEGFR2的Lys 920、Thr 916和Cys 919（2H）以及Glu 917形成了强氢键相互作用，且这些相互作用与抗血管生成化合物阿西替尼的相互作用相似。所有试验的显著结果表明，SEA提取物含有可能干扰VEGF诱导的癌症恶性发展的潜在抗血管生成化合物。
