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[6]-姜烯酚的非临床体外研究中的毒性、细胞遗传学和抗肿瘤评价。

Toxic, cytogenetic and antitumor evaluations of [6]-gingerol in non-clinical in vitro studies.

机构信息

Northeast Biotechnology Network (RENORBIO), Postgraduate Program in Biotechnology, Federal University of Piauí, Teresina, Piauí, 64049-550, Brazil.

Postgraduate Program in Pharmaceutical Sciences, Laboratory of Genetic Toxicology, Federal University of Piauí, Teresina, Piauí, 64049-550, Brazil.

出版信息

Biomed Pharmacother. 2019 Jul;115:108873. doi: 10.1016/j.biopha.2019.108873. Epub 2019 Apr 16.

Abstract

Gingerol - [6]-gingerol ((S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-3-decanone; [6]-G) - is a phenolic compound with several pharmacological properties. Herein, the aim of the study was to evaluate the toxicogenic effects of [6]-G on Artemia salina nauplii, Allium cepa, HL-60 cell line and Sarcoma 180 (S-180) ascitic fluid cells.For toxic and genotoxic analysis, it was used [6]-G concentrations of 5, 10, 20 and 40 μg mL-1. For cytotoxic evaluation using the MTT test (3- [4,5-dimethyl-thiazol-2-yl] -2,5-diphenyl tetrazolium bromide), serial [6]-G dilutions (1.56-100 μg mL-1) were performed, and S-180, HL-60 and peripheral blood mononuclear cells (PBMC) were treated for 72 h. The IC50 of [6]-G were 1.14, 5.73 and 11.18 μg mL-1 for HL-60, S-180 and PBMC, respectively, indicating a possible selectivity against tumor cell lines. At higher concentrations (>10 μg mL), toxicity and genotoxicity were observed in the A. cepa test, especially at 40 μg mL. Mechanisms indicating apoptosis, such as toxicity, cytotoxicity and nuclear abnormalities (bridges, fragments, delays, loose chromosomes and micronuclei) suggest that [6]-G has potential for antitumor pharmaceutical formulations.

摘要

姜辣素- [6]-姜辣素((S)-5-羟基-1-(4-羟基-3-甲氧基苯基)-3-癸酮; [6]-G) - 是一种具有多种药理特性的酚类化合物。在此,本研究的目的是评估 [6]-G 对卤虫无节幼体、洋葱、HL-60 细胞系和肉瘤 180(S-180)腹水细胞的毒性和遗传毒性作用。为了进行毒性和遗传毒性分析,使用了 5、10、20 和 40μg/mL 的 [6]-G 浓度。为了使用 MTT 试验(3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四氮唑溴化物)进行细胞毒性评估,进行了系列 [6]-G 稀释(1.56-100μg/mL),并用 S-180、HL-60 和外周血单核细胞(PBMC)处理 72 小时。HL-60、S-180 和 PBMC 的 [6]-G 的 IC50 分别为 1.14、5.73 和 11.18μg/mL,表明对肿瘤细胞系可能具有选择性。在较高浓度(>10μg/mL)时,在洋葱试验中观察到毒性和遗传毒性,尤其是在 40μg/mL 时。表明细胞凋亡的机制,如毒性、细胞毒性和核异常(桥、片段、延迟、松散染色体和微核)表明 [6]-G 具有抗肿瘤药物制剂的潜力。

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