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从合欢中分离得到的皂苷的体外抗肿瘤活性研究。

Anticancer activity of saponin isolated from Albizia lebbeck using various in vitro models.

机构信息

Maliba Pharmacy College, Bardoli, Surat, Gujarat, India.

Maliba Pharmacy College, Bardoli, Surat, Gujarat, India.

出版信息

J Ethnopharmacol. 2019 Mar 1;231:494-502. doi: 10.1016/j.jep.2018.11.004. Epub 2018 Nov 6.

DOI:10.1016/j.jep.2018.11.004
PMID:30408535
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Albizia lebbeck (L.) Benth. (Family: Mimosaceae) is commonly known as Sirisha in Sanskrit. The leaves and pods of A. lebbeck were claimed to be used against cancer in traditional medicine. Previous studies using bark, leaves, seeds and pods of A. lebbeck showed cytotoxic activity against hepatic, colon, larynx, cervical and breast cancer cell lines.

AIM OF THE STUDY

To evaluate the anticancer activity of saponin rich fraction of Albizia lebbeck by using various in vitro models.

MATERIALS AND METHODS

Albiziasaponins (A-E) are oleanene triterpene presents in Albizia lebbeck were used for in silico studies. In silico testing of albiziasaponins for structure based pharmacological activity prediction using PASS Online software and docking with Autodock tool and Autodock Vina revels it's anticancer and apoptogenic potential. Antiproliferative activity of saponin rich fraction of A. lebbeck was performed using MCF-7 human breast cancer cells by MTT assay methods. Anti-angiogenic property of saponin rich fraction of A. lebbeck was evaluated in in vitro shell less chick embryo cultures with different concentrations (0.1 µg/ml, 0.5 µg/ml, and 1 µg/ml) by using ImageJ software. In vitro cultured lymphocytes chromosomal aberration assay was performed to determine the physical integrity of chromosomes in cells and effect of saponin rich fraction of A. lebbeck on cell cycle. Apoptogenic potential was evaluated using Caspases-3 and Caspase-8 ELISA assay in MCF-7 cells.

RESULTS

Result of MTT assay showed IC50 of saponin rich fraction of A. lebbeck at 1 μg/ml in MCF-7 cells. Treatment with saponin rich fraction of A. lebbeck significantly (p < 0.05) reduced angiogenic parameters. Significant chromosomal aberrations (hypodiploid, hyperdiploid, ring, premature separation, Dicentric fragments, Acentric fragment, chromatid break, and chromosomal gap) were observed in saponin rich fraction of A. lebbeck treated groups. Treatment with saponin rich fraction of A. lebbeck increased levels of Caspases-3 (optical density of 0.24 at 450 nm) and Caspase-8 (optical density of 0.31 at 450 nm) as compared to staurosporine (optical density of 2.47 and 2.65 for caspases-3 and -8 respectively at 450 nm).

CONCLUSION

In our study, saponin rich fraction of A. lebbeck showed antiproliferative, antiangiogenic and apoptogenic potential using various in-vitro models. It also found to increase chromosomal aberration and thereby may affect cell cycle.

摘要

民族药理学相关性

金合欢(L.)Benth.(家族:含羞草科)在梵文中通常被称为 Sirisha。传统医学中,金合欢的叶子和豆荚据称可用于治疗癌症。先前使用金合欢的树皮、叶子、种子和豆荚进行的研究表明,它对肝癌、结肠癌、喉癌、宫颈癌和乳腺癌细胞系具有细胞毒性活性。

研究目的

使用各种体外模型评估金合欢皂苷丰富部分的抗癌活性。

材料和方法

使用存在于金合欢中的 Albiziasaponins(A-E)进行基于结构的药理学活性预测的计算机模拟研究。使用 PASS Online 软件和 Autodock 工具对 Albiziasaponins 进行基于结构的药理学活性预测的计算机模拟测试,并与 Autodock Vina 对接,揭示其抗癌和促凋亡潜力。使用 MTT 测定法在 MCF-7 人乳腺癌细胞中进行金合欢皂苷丰富部分的抗增殖活性测定。使用不同浓度(0.1µg/ml、0.5µg/ml 和 1µg/ml)的无壳鸡胚体外培养物,使用 ImageJ 软件评估金合欢皂苷丰富部分的抗血管生成特性。在体外培养的淋巴细胞染色体畸变试验中,测定金合欢皂苷丰富部分对细胞染色体的物理完整性和细胞周期的影响。使用 Caspases-3 和 Caspase-8 ELISA 测定法在 MCF-7 细胞中评估促凋亡潜力。

结果

MTT 测定结果表明,金合欢皂苷丰富部分在 MCF-7 细胞中的 IC50 为 1μg/ml。金合欢皂苷丰富部分处理显著(p<0.05)降低了血管生成参数。在金合欢皂苷丰富部分处理组中观察到明显的染色体畸变(亚二倍体、超二倍体、环、过早分离、双着丝粒片段、无着丝粒片段、染色单体断裂和染色体缺口)。与 staurosporine(Caspases-3 的光密度为 0.24 在 450nm,Caspase-8 的光密度为 0.31 在 450nm)相比,金合欢皂苷丰富部分处理组 Caspases-3(在 450nm 处的光密度为 0.24)和 Caspase-8(在 450nm 处的光密度为 0.31)的水平升高。

结论

在我们的研究中,金合欢皂苷丰富部分通过各种体外模型显示出抗增殖、抗血管生成和促凋亡潜力。它还发现增加染色体畸变,从而可能影响细胞周期。

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