Food & Function 2018-04-07

Hepatoprotective activity of iridoids, seco-iridoids and analogs glycosides from Gentianaceae on HepG2 cells via CYP3A4 induction and mitochondrial pathway

Kang Dai, Xue-Jia Yi, xianju Huang, Azhar Muhammad, Mei Li, Jun Li, Guang-Zhong Yang, Yue Gao

Index: 10.1039/C8FO00168E

Full Text: HTML

Abstract

Gentianaceae herbs extracts have been widely used as food additives, teas or medicinal remedies for various human body diseases and disorders. Here, the potential effects of the iridoids, seco-iridoids and analogs 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 analogs compounds from 50 gentian species to the active sites of human CYP3A4 enzyme. The docking scores of 29 iridoids, seco-iridoids and analogs 24 glycosides were calculated from free energy of ligand-protein complexes using computer-assisted docking simulation. After comprehensive evaluation, 6 of those 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 most obvious inductive effect on CYP3A4 mRNA levels in HepG2 cells. Moreover, amarogentin was further studied in acontine-induced toxicity in HepG2 cells to determine the potential mechanisms. Amarogentin treatment for 48 h dose-dependently attenuated the aconitine-mediated decrease of the mtDNA, ATP depletion, oxidative stress and ΔΨm loss of HepG2 hepatocytes. These results elucidate that the hepatoprotective effects are caused by facilitation of drug metabolism, amelioration of mitochondrial dysfunction and reduction of oxidative stress. Our data demonstrate that naturally found iridoids, seco-iridoids and analogs glycosides in gentian may be responsible for the hepatoprotective effects of gentian extracted compounds and thus may be useful in food industry or clinical practice.