Department of Nutritional Science and Toxicology, University of California, Berkeley, Berkeley, California 94720, United States.
J Agric Food Chem. 2012 Mar 14;60(10):2746-52. doi: 10.1021/jf204525b. Epub 2012 Mar 6.
Aromatic monoterpene, thymol, shows several beneficial activities, such as an antioxidative effect. However, the mechanism of its toxicity remains to be fully defined. In preliminary studies, thymol was characterized as a melanin formation inhibitor in an enzymatic system; however, thymol showed moderate cytotoxicity but not an antimelanogenic effect on B16-F10 melanoma cells. Thymol exhibited cytotoxicity, with an IC(50) value of 400 μM (60.09 μg/mL). This moderate toxic effect was suppressed with the addition of vitamin C and vitamin D, and 20 and 40% of cell viability was increased, respectively. Subsequently, the treatment of L-cysteine on thymol-treated melanoma cells reversed the toxic effect of thymol. Moreover, a significant oxidative stress condition was observed when B16 melanoma cells were cultured with thymol. In conclusion, the antioxidant actions of thymol generate a stable phenoxy radical intermediate, which generates reactive oxygen species and quinone oxide derivatives. Thus, it is proposed that the primary mechanism of thymol toxicity at high doses is due to the formation of antioxidant-related radicals.
芳香单萜，百里香酚，具有多种有益的活性，如抗氧化作用。然而，其毒性的机制仍有待充分定义。在初步研究中，百里香酚在酶系统中被表征为黑色素形成抑制剂；然而，百里香酚对 B16-F10 黑素瘤细胞表现出中等的细胞毒性，但没有抗黑色素生成作用。百里香酚表现出细胞毒性，IC50 值为 400 μM（60.09 μg/mL）。这种中等毒性作用可以通过添加维生素 C 和维生素 D 得到抑制，分别增加了 20%和 40%的细胞活力。随后，用 L-半胱氨酸处理百里香酚处理的黑素瘤细胞，逆转了百里香酚的毒性作用。此外，当 B16 黑素瘤细胞用百里香酚培养时，观察到明显的氧化应激状态。总之，百里香酚的抗氧化作用产生了稳定的苯氧自由基中间体，从而产生了活性氧和醌氧化物衍生物。因此，建议高剂量百里香酚毒性的主要机制是由于形成抗氧化相关的自由基。
