Department of Pharmaceutical Sciences, University of Bologna, Bologna, Italy.
Toxicol In Vitro. 2011 Feb;25(1):64-72. doi: 10.1016/j.tiv.2010.09.008. Epub 2010 Sep 18.
Guaiazulene (GA) is widely used as a natural ingredient in many health care products and solutions. Although it has been reported to have interesting biological effects, GA and azulene derivatives have been proven to be cytotoxic against normal human cells and human tumor cells; moreover, guaiazulene has shown photomutagenic properties on bacterial strains. Therefore, we evaluated and compared the cytotoxicity of GA at different concentrations on human gingival fibroblast (HGF) cell cultures under normal conditions and under UV irradiation (UV-A dose: 6.4 J/cm(2)). The compound tested was found to significantly reduce cell viability (dose-dependent trend, IC(50) 72.1 μM), decrease protein procollagen α1 type I synthesis, a marker for HGF protein, and COL1A1 mRNA expression. The cytotoxic effects were accompanied by activation of an intrinsic apoptotic pathway, studied using transmission electron microscopy (TEM) and caspase-3 activation. The light exposure of the cell culture treated decreased GA-induced cell death (IC(50) 128.9 μM), suggesting a photoprotective effect due to the photodegradation of the toxic agent, guaiazulene. Furthermore, the products of the photodegradation reaction of GA proved not to be toxic against HGFs.
Guaiazulene (GA) 被广泛用作许多保健产品和解决方案中的天然成分。尽管已经报道它具有有趣的生物学效应，但 GA 和薁衍生物已被证明对正常人类细胞和人类肿瘤细胞具有细胞毒性；此外，guiaiazulene 对细菌菌株表现出光致突变特性。因此，我们在正常条件和紫外线照射下（UV-A 剂量：6.4 J/cm(2)）评估并比较了 GA 在不同浓度下对人牙龈成纤维细胞 (HGF) 细胞培养物的细胞毒性。测试的化合物被发现显著降低细胞活力（剂量依赖性趋势，IC(50)72.1 μM），降低细胞外基质中 COL1A1 基因的表达，这是 HGF 蛋白的标志物，减少前胶原蛋白 α1 型 I 的合成。细胞毒性作用伴随着内在凋亡途径的激活，使用透射电子显微镜 (TEM) 和 caspase-3 激活进行研究。用 TEM 观察到细胞培养物经光照后，GA 诱导的细胞死亡减少（IC(50)128.9 μM），这表明由于有毒物质 guaiazulene 的光降解，存在光保护作用。此外，GA 光降解反应的产物对 HGFs 没有毒性。
