体外和体内评价从雪松Cedrus Libani分离出来的2-Himachelen-7-ol的抗癌和抗炎活性。,Scientific Reports

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体外和体内评价从雪松Cedrus Libani分离出来的2-Himachelen-7-ol的抗癌和抗炎活性。
Scientific Reports ( IF 3.8 ) Pub Date : 2019-09-06 , DOI: 10.1038/s41598-019-49374-9
Andree Elias ₁ , Wassim N Shebaby ₁ , Bilal Nehme ₁ , Wissam Faour ₂ , Bassem S Bassil ₃ , Joelle El Hakim ₁ , Rita Iskandar ₁ , Nahia Dib-Jalbout ₁ , Mohamad Mroueh ₄ , Costantine Daher ₁ , Robin I Taleb ₁

Affiliation

雪松柏（Cedrus libani）是雄伟的常绿树，原产于黎巴嫩，叙利亚和土耳其的地中海山脉。在这项研究中，使用己烷提取心木，以生产深色油状梭状芽孢杆菌油提取物（CLOE）。对CLOE的GCMS分析确定了多达30种化合物，其中2-himachalen-7-ol（7-HC）含量最高（40％）。使用柱色谱法分离7-HC，并通过NMR光谱法和X-射线晶体学确认白色结晶固体的身份。7-HC对多种人类癌细胞系（包括脑（SF-268，IC50 8.1μg/ mL）和结肠（HT-29，IC50 10.1μg/ mL; Caco-2，IC50 9.9μg/ mL））表现出强大的细胞毒性活性。卵巢细胞（Sk-OV-3，IC50> 50μg/ mL）耐药性最高。但是，尽管HT-29对顺铂显示出抗性，但7-HC的效力却高8-10倍。与7-HC和顺铂的共同治疗显示出对SF-268，HT-29和Caco-2细胞的显着协同抗增殖作用。7-HC在福尔马林诱导的大鼠足水肿中也表现出显着的抗炎作用。蛋白质印迹分析显示，7-HC在分离的大鼠单核细胞中显示出LPS诱导的COX-2蛋白表达的剂量依赖性抑制。本研究表明7-HC具有有希望的抗癌和抗炎活性，并且可以作为癌症治疗中的先导分子。蛋白质印迹分析显示，7-HC在分离的大鼠单核细胞中显示出LPS诱导的COX-2蛋白表达的剂量依赖性抑制。本研究表明7-HC具有有希望的抗癌和抗炎活性，并且可以作为癌症治疗中的先导分子。蛋白质印迹分析显示，7-HC在分离的大鼠单核细胞中显示出LPS诱导的COX-2蛋白表达的剂量依赖性抑制。本研究表明7-HC具有有希望的抗癌和抗炎活性，并且可以作为癌症治疗中的先导分子。

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In Vitro and In Vivo Evaluation of the Anticancer and Anti-inflammatory Activities of 2-Himachelen-7-ol isolated from Cedrus Libani.

Cedrus libani is a majestic evergreen tree native to the Mediterranean mountains of Lebanon, Syria and Turkey. In this study, the tree heart wood was extracted using hexane to produce C. libani oil extract (CLOE) as a dark oil. GCMS analysis of CLOE identified up to 30 compounds whereby 2-himachalen-7-ol (7-HC) was the most abundant (40%). 7-HC was isolated using column chromatography and the identity of the white crystalline solid was confirmed via NMR spectroscopy and X-Ray Crystallography. 7-HC demonstrated potent cytotoxic activity against several human cancer cell lines including brain (SF-268, IC50 8.1 μg/mL) and colon (HT-29, IC50 10.1 μg/mL; Caco-2, IC50 9.9 μg/mL) with ovarian (Sk-OV-3, IC50 > 50 μg/mL) cells being the most resistant. However, while HT-29 displayed resistance to Cisplatin, 7-HC was 8-10 folds more potent. Co-treatment with 7-HC and Cisplatin showed a significant synergistic anti-proliferative effect against SF-268, HT-29 and Caco-2 cells. 7-HC also exhibited significant anti-inflammatory effect in formalin-induced paw edema in rats. Western blot analysis revealed that 7-HC displayed dose dependent inhibition of LPS-induced COX-2 protein expression in isolated rat monocytes. The present study demonstrates that 7-HC possesses promising anticancer and anti-inflammatory activities, and may serve as a lead molecule in cancer therapy.

更新日期：2019-09-06

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