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体外、计算和体内研究表明,粗甲醇提取物对 DEN 诱导的 HCC 具有抗肿瘤活性。

In vitro, In silico and In vivo Antitumor Activity of Crude Methanolic Extract of Tetilla dactyloidea (Carter, 1869) on DEN Induced HCC in a Rat Model.

机构信息

Department of Advanced Zoology and Biotechnology, Loyola College, Chennai - 600034, Tamil Nadu, India.

Department of Advanced Zoology and Biotechnology, Loyola College, Chennai - 600034, Tamil Nadu, India.

出版信息

Biomed Pharmacother. 2017 Nov;95:795-807. doi: 10.1016/j.biopha.2017.08.054. Epub 2017 Sep 10.

DOI:10.1016/j.biopha.2017.08.054
PMID:28892791
Abstract

Tetilla dactyloidea (Carter, 1869) is a marine sponge classified under Demospongia and recent studies have demonstrated that active constituents of Demospongia class have exhibited several potential medical applications. However, no preliminary pharmacological studies have been reported so far. The present investigation was carried out to evaluate the zoo-chemical status, antioxidant potential and anticancer activity of Crude Methanolic Extract of Tetilla dactyloidea (CMETD). Hepatocellular Carcinoma (HCC) was induced in the liver of male Sprague Dawley (SD) rats by treating with diethylnitrosamine (DEN). Nodule incidence, body weight, liver marker enzymes, enzymatic and non-enzymatic antioxidant, phase I metabolizing and liver macromolecular damaging enzymes and immuno-histopathological changes were assessed in DEN and DEN+CMETD treated rats. Oral administration of CMETD at a dose of 400mg/kg body weight to DEN treated rats restored the above parameters to near normal levels compared to control. The biochemical results were consistent with histopathological observations suggesting marked hepatoprotective effect of CMETD in a dose dependent manner. The GCMS of CMETD analysis showed the presence of six compounds. In in silico analysis 9-Octadecenoic acid (Z)-, 2-hydroxy-1-(hydroxymethyl) ethyl ester ligand showed an effective binding energy of -7.1kcal/mol against Cox-2 receptor. The compounds showed desirable pharmacokinetic properties and significant molecular interactions with the HCC receptors. To conclude, our results clearly suggested that CMETD treatment prevented liver damage, protected the antioxidant defense system and possessed anti-carcinogenic potential in DEN induced hepatic carcinoma.

摘要

指形软海绵(Carter,1869)是一种海洋海绵,属于多孔动物门。最近的研究表明,多孔动物门的活性成分具有多种潜在的医学应用。然而,到目前为止,还没有报道任何初步的药理学研究。本研究旨在评估指形软海绵(Tetilla dactyloidea)的粗甲醇提取物(CMETD)的动物化学状态、抗氧化潜力和抗癌活性。雄性 Sprague Dawley(SD)大鼠通过用二乙基亚硝胺(DEN)处理肝脏来诱导肝细胞癌(HCC)。在 DEN 和 DEN+CMETD 处理的大鼠中评估了结节发生率、体重、肝标志物酶、酶和非酶抗氧化剂、I 相代谢和肝大分子损伤酶以及免疫组织病理学变化。与对照组相比,以 400mg/kg 体重口服给予 CMETD 可使 DEN 处理的大鼠上述参数恢复接近正常水平。生化结果与组织病理学观察一致,表明 CMETD 具有明显的剂量依赖性肝保护作用。CMETD 的 GCMS 分析显示存在六种化合物。在计算机分析中,9-Octadecenoic acid(Z)-,2-hydroxy-1-(hydroxymethyl)ethyl ester 配体对 Cox-2 受体表现出有效的结合能-7.1kcal/mol。这些化合物表现出良好的药代动力学特性,并与 HCC 受体具有显著的分子相互作用。总之,我们的结果清楚地表明,CMETD 治疗可预防肝损伤,保护抗氧化防御系统,并具有 DEN 诱导的肝癌的抗癌潜力。

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