Berg Kerstin, Braun Christine, Krug Isabel, Schrenk Dieter
Food Chemistry and Toxicology, University of Kaiserslautern, Erwin-Schrödinger-Str. 52, 67663 Kaiserslautern, Germany.
Food Chemistry and Toxicology, University of Kaiserslautern, Erwin-Schrödinger-Str. 52, 67663 Kaiserslautern, Germany.
Toxicology. 2015 Jan 2;327:47-52. doi: 10.1016/j.tox.2014.10.001. Epub 2014 Oct 13.
Ginkgolic acids (GAs) are alkylphenols which can be found in the fruits and leaves of Ginkgo biloba L. (Ginkgoaceae) used in herbal teas, drugs and food supplements. Standardized leaf extracts of G. biloba are widely used in the therapy of cognitive decline including Alzheimer's diseases. However, GAs are known to have cytotoxic and allergenic potential and are suspected to possess genotoxic properties. Therefore, we examined in this study the cytotoxicity and mutagenicity of three major GAs with different alkyl or alkenyl groups (13:0, 15:1, 17:1). Cytotoxicity was assessed in male Chinese hamster lung fibroblasts (V79 cells) using the resazurin reduction assay. The substances showed concentration dependent cytotoxic effects after 24h of incubation at concentrations of 50μM and higher. Mutagenicity was determined by using the Ames fluctuation assay in different Salmonella typhimurium strains (TA97a, TA98, TA100 and TA102) with and without exogenous metabolic activation (S9 mix). Furthermore, we analyzed the mutagenic potency of the three major GAs in V79 cells by performing the hypoxanthine phosphoribosyl transferase (HPRT) assay which detects gene mutations at the HPRT locus. None of the mutagenic assays showed any increase in mutagenicity above background. Therefore, these data provide evidence that the GAs tested have some cytotoxic potency but are not mutagenic. Thus, our findings contribute to the risk assessment of preparations containing plant extracts from G. biloba.
银杏酸（GAs）是一种烷基酚，可在银杏科植物银杏的果实和叶子中找到，这些果实和叶子被用于制作花草茶、药物和食品补充剂。银杏叶的标准化提取物被广泛用于治疗包括阿尔茨海默病在内的认知衰退。然而，已知银杏酸具有细胞毒性和致敏潜力，并且被怀疑具有遗传毒性。因此，我们在本研究中检测了三种具有不同烷基或烯基（13:0、15:1、17:1）的主要银杏酸的细胞毒性和致突变性。使用刃天青还原试验在雄性中国仓鼠肺成纤维细胞（V79细胞）中评估细胞毒性。在50μM及更高浓度下孵育24小时后，这些物质表现出浓度依赖性细胞毒性作用。通过在不同的鼠伤寒沙门氏菌菌株（TA97a、TA98、TA100和TA102）中进行Ames波动试验来测定致突变性，试验有或没有外源性代谢激活（S9混合物）。此外，我们通过进行次黄嘌呤磷酸核糖基转移酶（HPRT）试验分析了三种主要银杏酸在V79细胞中的致突变潜力，该试验可检测HPRT位点的基因突变。没有一个致突变试验显示出致突变性高于背景值。因此，这些数据提供了证据，表明所测试的银杏酸具有一定的细胞毒性，但没有致突变性。因此，我们的研究结果有助于对含有银杏植物提取物的制剂进行风险评估。
