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

Abstract

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.

Veratrilla baillonii Franch Could Alleviate Lipid Accumulation in LO2 Cells by Regulating Oxidative, Inflammatory, and Lipid Metabolic Signaling Pathways

“…It can regulate the expression of liver detoxification and antioxidant defense genes (Kathirvel et al, 2010). Preliminary results indicate that WVBF can regulate the NRF2 pathway, WVBF treatment of NAFLD cells increased intracellular Nrf2 expression in a dose-dependent manner, suggesting that the antioxidant potential of WVBF could be an important mechanism for improving liver function of NAFLD cells, which is similar to the results of our previous study (Dai et al, 2018).…”

“…The water extract of V. baillonii (WVBF), which contain flavonoids, iridoid glycosides, and other substances (Vaidya et al, 2009;Ge et al, 2016;Yu et al, 2016;Zhang S. R. et al, 2018;Li et al, 2019). WVBF has significant protective effects on oxidative stress-induced liver injury (Dai et al, 2018), diabetic liver injury (Lian et al, 2010), and drug liver toxicity (Huang et al, 2016). However, the effects and underlying mechanism of V. baillonii in NAFLD are still unclear.…”

The Effects of Natural Iridoids and Anthocyanins on Selected Parameters of Liver and Cardiovascular System Functions

“…Researchers particularly focused on six popular iridoid compounds: gentiopicroside, sweroside, swertiamarin, loganic acid, 6-O-β-d-glucosyl-gentiopicroside, and amarogentin. In particular, the latter showed a significant inductive effect on CYP3A4 mRNA levels in HepG2 cells, as well as in the case of acontine-induced toxicity [16]. These results are consistent with the previously published work of other researchers who confirmed the effectiveness of amarogentin on carbon tetrachloride-induced liver fibrosis in mice.…”

“…Iridoids are found in the green parts of plants, mainly in the leaves and young stems, and sometimes in fruits and sprouts. Among the most commonly mentioned iridoids in the therapeutic context, the following stand out above all: gentiopicroside, geniposide, sweroside, loganin, loganic acid, catalpol, and amarogentin ( Figure 1) [8,[11][12][13][14][15][16][17][18][19][20][21][22][23][24][25].…”

Gentiopicroside Ameliorates Oxidative Stress and Lipid Accumulation through Nuclear Factor Erythroid 2-Related Factor 2 Activation

“…GPS is extracted from roots and rhizomes of Gentianaceae, and iridoid glycosides are the main active component of GPS. Several researchers have theoretically investigated that GPS has the function of antioxidation and liver protection [20,21]. However, the association between GPS and PI3K/Akt/Nrf2 signal has not been investigated in NAFLD.…”