Root of Gentiana lutea commercially available as gentian root, a natural antidote for different types of poisons, possess antioxidative, immunomodulatory, cytoprotective and anti-inflammatory, and adverse, genotoxic and mutagenic effects. It has monoterpenes loganic acid, swertiamarin, gentiopicroside and sweroside as most abundant constituents. In this study, we assessed the toxicity of monoterpenes’ reactive molecular fragments using in silico prediction by VEGA-QSAR platform. Further, we compared the data obtained with in vitro geno- and cyto- toxicity testing of the above monoterpenes and the G. lutea root extract (GE), on human primary unstimulated and mitogen-stimulated peripheral blood mononuclear cells (PBMCs). Viability was assessed by TB and XTT tests after 48 h treatment. DNA damage was evaluated by alkaline comet assay on unstimulated cells, whereas cytokinesis-block micronucleus assay was employed on mitogen-stimulated PBMCs. Stability of compounds throughout treatment was monitored by UPLC. The observed in vitro results had highest compliance with in silico IRFMN/ISSCAN-CGX prediction model. Compounds showed high stability during experiment while treatment with single compounds reduced number of viable cells and increased DNA damage. GE treatment had toxic impact on unstimulated PBMCs but no significant genotoxic influence on mitogen-stimulated PBMCs. In summary, the mild GE effect suggests that the complexity of crude GE extract chemical composition may attenuate the toxicity of the tested monoterpenes loganic acid, swertiamarin, gentiopicroside and sweroside.

中文翻译：

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龙胆根提取物及其单萜化合物的毒性评估

的根黄龙胆市售龙胆根，对不同类型的毒药的天然解毒剂，抗氧化具备，免疫调节，细胞保护和抗发炎，且不良，遗传毒性和诱变作用。它具有单萜类的鼠尾酸，stertiamarin，龙胆苦苷和sweroside作为最丰富的成分。在这项研究中，我们使用VEGA-QSAR平台进行计算机预测，评估了单萜类反应性分子片段的毒性。此外，我们比较了获得的数据在体外上述单萜geno-和cyto-毒性测试和G.黄体根提取物（GE），用于人类原代未刺激和有丝分裂原刺激的外周血单核细胞（PBMC）。治疗48小时后，通过TB和XTT测试评估生存力。通过对未刺激的细胞进行碱彗星试验评估DNA损伤，而对有丝分裂原刺激的PBMC采用胞质阻滞微核试验。通过UPLC监测整个治疗过程中化合物的稳定性。观察到的体外结果与计算机模拟的一致性最高IRFMN / ISSCAN-CGX预测模型。化合物在实验过程中显示出高稳定性，而用单一化合物处理可减少活细胞数量并增加DNA损伤。GE处理对未刺激的PBMC具有毒性影响，但对促分裂原刺激的PBMC没有明显的遗传毒性影响。总而言之，温和的GE效应表明，GE粗提物化学成分的复杂性可能会减弱所测试的单萜类对数酸，斯威蒂马林，龙胆苦味子苷和苦味子苷的毒性。