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从黎巴嫩雪松中分离得到的 2-海美香醇-7-醇的体外和体内抗癌和抗炎活性评价。

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

机构信息

Department of Natural Sciences, Lebanese American University, Byblos, 1102 2801, Lebanon.

School of Medicine, Lebanese American University, Byblos, 1102 2801, Lebanon.

出版信息

Sci Rep. 2019 Sep 6;9(1):12855. doi: 10.1038/s41598-019-49374-9.

Abstract

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, IC 8.1 μg/mL) and colon (HT-29, IC 10.1 μg/mL; Caco-2, IC 9.9 μg/mL) with ovarian (Sk-OV-3, IC > 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.

摘要

雪松木是一种原产于黎巴嫩、叙利亚和土耳其地中海山脉的雄伟常绿乔木。在这项研究中,使用己烷从树心中提取雪松油提取物(CLOE),得到一种深棕色油。GCMS 分析 CLOE 鉴定出多达 30 种化合物,其中 2-扁柏烯-7-醇(7-HC)含量最丰富(40%)。7-HC 采用柱层析法分离,通过 NMR 光谱和 X 射线晶体学确认了白色结晶固体的结构。7-HC 对多种人类癌细胞系表现出强烈的细胞毒性,包括脑(SF-268,IC8.1μg/mL)和结肠(HT-29,IC10.1μg/mL;Caco-2,IC9.9μg/mL),而卵巢(Sk-OV-3,IC>50μg/mL)细胞的耐药性最强。然而,虽然 HT-29 对顺铂有耐药性,但 7-HC 的效力高出 8-10 倍。7-HC 与顺铂联合治疗对 SF-268、HT-29 和 Caco-2 细胞显示出显著的协同抗增殖作用。7-HC 还在大鼠福尔马林诱导的爪肿胀模型中显示出显著的抗炎作用。Western blot 分析显示,7-HC 对 LPS 诱导的大鼠单核细胞中 COX-2 蛋白表达具有剂量依赖性抑制作用。本研究表明,7-HC 具有有前途的抗癌和抗炎活性,可能成为癌症治疗的先导分子。

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