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.

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This manuscript was aimed to explore the hepato-protective effect of water extract of Veratrilla baillonii Franch. (Gentianaceae) (WVBF) on serious hepatic toxicity induced in mice treated with Aconitum brachypodum Diels (Ranunculaceae) at transcriptome level. The physiological and pathological symptoms were evaluated as the markers for hepato toxicity induced by A. brachypodum Diels (CFA) extracted compounds. Moreover, gene chip method was used to compare and investigate the gene expression level of WVBF on CFA induced-liver toxicity to identify the potential target of WVBF and CFA on liver. The results showed that WVBF had a significant detoxification effect on CFA-induced acute hepatic toxicity. There were 130 genes with lower expression and 124 genes expressed at higher rate in CFA treated group as compared with normal control group, while there are 67 genes down-regulated and 74 genes up-regulated in WVBF treated group in comparison with CFA treated group. WVBF could attenuate CFA-induced liver damage in mice through regulating oxidative stress, inflammatory injury and cell apoptosis/necrosis pathways. On the other hand, WVBF and CFA may have potential synergetic effects on the target genes of certain diseases such as inflammation, cancer and diabetes.