Gentianaceae herb extracts have been widely used as food additives, teas or medicinal remedies for various diseases and disorders of the human body. Herein, the potential effects of iridoids, seco-iridoids and analog glycosides from gentian on acontine-induced hepatotoxicity were investigated in HepG2 cells to obtain metabolic data of drug-biotarget interactions. Molecular docking analysis was performed to assess the binding efficiencies of 53 iridoids, seco-iridoids and analog compounds obtained from 50 gentian species to the active sites of human CYP3A4 enzyme. The docking scores of 29 iridoids, seco-iridoids and 24 analog glycosides were calculated from the free energy of ligand–protein complexes using a computer-assisted docking simulation. After comprehensive evaluation, 6 of these compounds, i.e., gentiopicroside, sweroside, swertiamarin, loganic acid, 6-O-β-D-glucosyl-gentiopicroside and amarogentin were selected to evaluate their hepatoprotective effects. Quantitative real-time PCR was used to measure the expression levels of CYP3A4 mRNA in HepG2 cells. Amarogentin displayed the most clear inductive effect on CYP3A4 mRNA levels in the HepG2 cells. Moreover, amarogentin was further studied for acontine-induced toxicity in the HepG2 cells to determine the potential mechanisms. Amarogentin displayed obvious inductive effect on CYP3A4 mRNA levels in the HepG2 cells. These results elucidated that the hepatoprotective effects were caused by the facilitation of drug metabolism, amelioration of mitochondrial dysfunction and reduction of oxidative stress. Our data demonstrated that the naturally found iridoids, seco-iridoids and analog glycosides in gentian may be responsible for the hepatoprotective effects of gentian-extracted compounds and thus, this study may be useful in the food industry or in clinical practice.

中文翻译：

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龙胆科的环烯醚草酮，癸二糖苷和类似物苷通过CYP3A4诱导和线粒体途径对HepG2细胞的保肝活性†

龙胆科草药提取物已被广泛用作食品添加剂，茶或用于治疗人体各种疾病的药物。在本文中，研究了来自龙胆的鸢尾酮，癸二糖皮质激素和类似物苷对HepG2细胞中阿仑替尼诱导的肝毒性的潜在影响，以获得药物-生物靶相互作用的代谢数据。进行了分子对接分析以评估从50个龙胆物种获得的53种鸢尾，类脂环糊精和类似化合物与人CYP3A4酶活性位点的结合效率。使用计算机辅助的对接模拟，根据配体-蛋白质复合物的自由能，计算出29种环烯醚酮，癸二糖苷和24种类似糖苷的对接分数。经过综合评估，这些化合物中有6种，即，龙胆苦苷，苦参碱，苦参碱，对数酸，6- O- β- D选择了葡糖基-龙胆苦苷和a青素以评估其对肝脏的保护作用。实时荧光定量PCR检测CYP3A4 mRNA在HepG2细胞中的表达水平。Amarogentin对HepG2细胞中的CYP3A4 mRNA水平显示出最明显的诱导作用。此外，进一步研究了Amarogentin在HepG2细胞中的阿Continent诱导的毒性，以确定潜在的机制。Amarogentin对HepG2细胞中CYP3A4 mRNA的表达具有明显的诱导作用。这些结果阐明了肝保护作用是由促进药物代谢，减轻线粒体功能障碍和减轻氧化应激引起的。我们的数据表明，自然发现的虹彩，