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百里香叶石蚕提取物的乙酸乙酯部分通过抑制细胞增殖/血管内皮生长因子分泌,消除了人脐静脉内皮细胞(HUVEC)在胶原床中的管状形成。

Ethyl Acetate Fraction of Teucrium Polium Extract Abolishes Human Umbilical Vein Endothelial Cells (HUVEC) Tubulogenesis in Collagen Bed through Suppression of Cell Proliferation/VEGF Secretion.

作者信息

Askari Vahide, Shamlou Somayeh, Mostafaie Ali, Khaleqi Sara

机构信息

Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran AND Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.

出版信息

Iran J Allergy Asthma Immunol. 2019 Jun 8;18(3):281-288. doi: 10.18502/ijaai.v18i3.1121.

DOI:10.18502/ijaai.v18i3.1121
PMID:31522435
Abstract

Angiogenesis has essential role in growth and metastasis of tumors. Development of therapies aimed to suppress angiogenesis using medicinal plants is one of the effective approaches for prevention/treatment of cancer. The current study was performed to investigate in vitro anti-angiogenic effect of Teucrium Polium (TP) extract and its fractions. The aerial part of Teucrium Polium was powdered and extracted with 50% ethanol. The extract was fractionated in to aqueous (AQ), n-butanol (BU), ethyl acetate (EA) and n-hexane (HE) fractions. Anti-angiogenic effect of TP was examined on human umbilical vein endothelial cells (HUVECs) in three-dimensional collagen matrix. The endothelial cells form capillary-like branches that can be visualized using phase contrast microscope and the number of tube-like structures can be quantified as a measure of in vitro angiogenesis. Furthermore, anti-proliferative and vascular endothelial growth factor(VEGF )suppressive effect of TP as important factors in the process of angiogenesis were assessed using3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT)and quantitative ELISA, respectively. Based on our findings, among the TP fractions, EA fraction showed the highest inhibitory activity on angiogenesis. This fraction with IC50: 68 µg/mL, inhibited angiogenesis at 60 µg/mL. The crude extract and other fractions of TP inhibited angiogenesis in a dose-dependent manner at doses higher concentrations than EA fraction, significantly.TP extract and EA fraction were able to inhibit proliferation of HUVEC and inhibited VEGF secretion in a dose dependent manner. The ethyl acetate fraction at 60 µg/ml inhibited VEGF secretion perfectly. Our data indicated that ethyl acetate fraction of Teucrium Polium could be a potential candidate for the prevention of angiogenesis in cancer and other related disorders. However, this suggestion needs more quantitative and in vivo investigations for confirmation.

摘要

血管生成在肿瘤的生长和转移中起着至关重要的作用。利用药用植物开发旨在抑制血管生成的疗法是预防/治疗癌症的有效方法之一。本研究旨在探讨香青兰提取物及其馏分的体外抗血管生成作用。将香青兰地上部分粉碎,用50%乙醇提取。提取物被分离成水相(AQ)、正丁醇(BU)、乙酸乙酯(EA)和正己烷(HE)馏分。在三维胶原基质中检测香青兰对人脐静脉内皮细胞(HUVECs)的抗血管生成作用。内皮细胞形成毛细血管样分支,可通过相差显微镜观察,管状结构的数量可作为体外血管生成的指标进行量化。此外,分别使用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)和定量ELISA评估香青兰作为血管生成过程中重要因素的抗增殖和血管内皮生长因子(VEGF)抑制作用。根据我们的数据,在香青兰馏分中,EA馏分对血管生成的抑制活性最高。该馏分的IC50为68 μg/mL,在60 μg/mL时抑制血管生成。香青兰粗提物和其他馏分在高于EA馏分的浓度下以剂量依赖方式显著抑制血管生成。香青兰提取物和EA馏分能够抑制HUVEC的增殖,并以剂量依赖方式抑制VEGF分泌。60 μg/ml的乙酸乙酯馏分能完美抑制VEGF分泌。我们的数据表明,香青兰的乙酸乙酯馏分可能是预防癌症和其他相关疾病中血管生成的潜在候选物。然而,这一建议需要更多的定量和体内研究来证实。

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引用本文的文献

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Medicinal Plants Extracts with Antiangiogenic Activity: Where Is the Link?具有抗血管生成活性的药用植物提取物:联系何在?
Adv Pharm Bull. 2020 Jul;10(3):370-378. doi: 10.34172/apb.2020.045. Epub 2020 May 11.