Grollino Maria Giuseppa, Raschellà Giuseppe, Cordelli Eugenia, Villani Paola, Pieraccioli Marco, Paximadas Irene, Malandrino Salvatore, Bonassi Stefano, Pacchierotti Francesca
Laboratory of Biosafety and Risk Assessment, ENEA CR Casaccia, Via Anguillarese 301, 00123 Rome, Italy.
Laboratory of Biosafety and Risk Assessment, ENEA CR Casaccia, Via Anguillarese 301, 00123 Rome, Italy.
Food Chem Toxicol. 2017 Nov;109(Pt 1):486-496. doi: 10.1016/j.fct.2017.09.042. Epub 2017 Sep 22.
The use of Ginkgo biloba leaf extract as nutraceutical is becoming increasingly common. As a consequence, the definition of a reliable toxicological profile is a priority for its safe utilization. Recently, contrasting data have been reported on the carcinogenic potential of Ginkgo biloba extract in rodent liver. We measured viability, Reactive Oxygen Species (ROS), apoptosis, colony-forming efficiency, genotoxicity by comet assay, and gene expression changes associated with hepato-carcinogenicity in human cells of hepatic origin (HepG2 and THLE-2) treated with different concentrations (0.0005-1.2 mg/mL) of GinkgoselectPlus. Our analyses highlighted a decrease of cell viability, not due to apoptosis, after treatment with high doses of the extract, which was likely due to ROS generation by a chemical reaction between extract polyphenols and some components of the culture medium. Comet assay did not detect genotoxic effect at any extract concentration. Finally, the array analysis detected a slight decrease in the expression of only one gene (IGFBP3) in Ginkgo-treated THLE-2 cells as opposed to changes in 28 genes in Aflatoxin B1 treated-cells. In conclusion, our results did not detect any significant genotoxic or biologically relevant cytotoxic effects and gross changes in gene expression using the Ginkgo extract in the hepatic cells tested.
银杏叶提取物作为营养保健品的使用正变得越来越普遍。因此，确定可靠的毒理学特征对于其安全使用至关重要。最近，关于银杏叶提取物在啮齿动物肝脏中的致癌潜力，已有相互矛盾的数据报道。我们用不同浓度（0.0005 - 1.2 mg/mL）的GinkgoselectPlus处理肝源性人细胞（HepG2和THLE - 2），测量了细胞活力、活性氧（ROS）、细胞凋亡、集落形成效率、彗星试验检测的遗传毒性以及与肝癌发生相关的基因表达变化。我们的分析强调，高剂量提取物处理后细胞活力下降，但并非由细胞凋亡引起，这可能是由于提取物中的多酚与培养基中的某些成分发生化学反应产生了ROS。在任何提取物浓度下，彗星试验均未检测到遗传毒性作用。最后，阵列分析检测到，与黄曲霉毒素B1处理的细胞中28个基因发生变化相反，银杏叶处理的THLE - 2细胞中仅一个基因（IGFBP3）的表达略有下降。总之，我们的结果表明，在所测试的肝细胞中，使用银杏叶提取物未检测到任何显著的遗传毒性或生物学相关的细胞毒性作用以及基因表达的总体变化。
