Universidade de Franca, Franca, Brazil.
Institute of Natural Sciences - Federal University of Alfenas, Alfenas, Brazil.
Drug Chem Toxicol. 2022 May;45(3):1302-1307. doi: 10.1080/01480545.2020.1822389. Epub 2020 Oct 13.
This study evaluated the cytotoxic, genotoxic, and the modulatory effects on DNA damage of hypericin in Chinese hamster lung fibroblasts (V79 cells). The hypericin is a natural polycyclic quinone, mainly extracted from St. John's Wort ( L.). Along with hyperforin, the hypericins are responsible for the antidepressant activity of St. John's Wort. Cytotoxicity was assessed by the XTT colorimetric assay and the nuclear division index (NDI). The genotoxic activity was studied by the micronucleus test at concentrations of 30, 60, 120, and 240 μg/mL. Mutagenic agents, methyl methanesulfonate (MMS, 44 μg/mL), doxorubicin (DXR, 0.5 μg/mL), and etoposide (VP16, 1 μg/mL) were used in combination with different concentrations of hypericin in order to evaluate the modulatory effect on DNA damage. Results showed that the hypericin was cytotoxic at concentrations above 156.2 μg/mL and genotoxic above 120 μg/mL. The hypericin significantly reduced DNA damage frequency induced by DXR, at concentrations of 30 and 60 μg/mL, and MMS at a concentration of 30 μg/mL, but was unable to reduce damage when combined with VP-16. These results demonstrate the non-photoactivated hypericin toxicological safety limits, its protective effect on DNA damage and provide a basis for future studies that may characterize better its chemopreventive mechanism.
本研究评估了金丝桃素对中国仓鼠肺成纤维细胞(V79 细胞)的细胞毒性、遗传毒性和 DNA 损伤的调节作用。金丝桃素是一种天然多环醌,主要从贯叶连翘(L.)中提取。与金丝桃素一样,金丝桃素类化合物是贯叶连翘抗抑郁作用的主要成分。通过 XTT 比色法和核分裂指数(NDI)评估细胞毒性。在 30、60、120 和 240μg/mL 浓度下通过微核试验研究遗传毒性活性。将甲基甲磺酸酯(MMS,44μg/mL)、阿霉素(DXR,0.5μg/mL)和依托泊苷(VP16,1μg/mL)等诱变剂与不同浓度的金丝桃素组合使用,以评估对 DNA 损伤的调节作用。结果表明,金丝桃素在浓度高于 156.2μg/mL 时具有细胞毒性,在浓度高于 120μg/mL 时具有遗传毒性。金丝桃素在 30 和 60μg/mL 浓度下显著降低了 DXR 诱导的 DNA 损伤频率,在 30μg/mL 浓度下也降低了 MMS 的损伤频率,但与 VP-16 联合使用时无法降低损伤频率。这些结果表明非光活化金丝桃素的毒性安全限制,其对 DNA 损伤的保护作用,并为未来可能更好地表征其化学预防机制的研究提供了依据。