Induction of cytochrome P450 1A1 expression by ginsenoside Rg1 and Rb1 in HepG2 cells
ABSTRACT Transcriptional activation of the human CYP1A1 gene (coding for cytochrome P450 1A1) is mediated by the aryl hydrocarbon receptor. In the present study we have examined interaction of the ginsenoside Rg1 and Rb1 with the carcinogen activation pathway mediated by the aryl hydrocarbon receptor in HepG2 cells. RT-PCR was used to determine the CYP1A1 mRNA levels. The results showed that in HepG2 cells CYP1A1 mRNA expression was significantly increased in a concentration- and time- dependent manner by ginsenoside Rg1 and Rb1. Ginsenoside Rg1 and Rb1 activated the DNA-binding capacity of the aryl hydrocarbon receptor for the xenobiotic responsive element of CYP1A1 as measured by the electrophoretic-mobility shift assay (EMSA). Rg1 and Rb1 were able to activate the ability of the aryl hydrocarbon receptor to bind to an oligonucleotide containing the xenobiotic-responsive element (XRE) of the cyp1a1 promoter. These results indicate that Rg1 and Rb1's effects on CYP1A1 induction are mediated by the aryl hydrocarbon receptor. Since CYP1A1 and aryl hydrocarbon receptor play important roles in carcinogenesis, development, differentiation and many other essential physiological functions, these results suggest that the chemopreventive effect of Panax ginseng may be due, in part, to ginsenoside Rg1 and Rb1's ability to compete with aryl hydrocarbons for both the aryl hydrocarbon receptor and CYP1A1. Rg1 and Rb1 may thus be natural ligands and substrates of the aryl hydrocarbon receptor or have relationship with aryl hydrocarbon receptor pathway. These properties might be of help for future studies in P. ginseng and chemoprevention in chemical-induced cancer.
- SourceAvailable from: Donghua Hu[Show abstract] [Hide abstract]
ABSTRACT: Artemisinin has been used to treat malaria for centuries in the context of traditional Chinese medicine. In the present study, the effects of artemisinin on pregnane X receptor (PXR)-mediated CYP3A expression and its therapeutic role in inflammatory bowel disease were investigated. LS174T cells exposed to artemisinin at various concentrations and for different periods of time were examined with respect to the specific induction of CYP3A4 and PXR mRNA expression. Transient transfection experiments showed transcriptional activation of the CYP3A4 gene through artemisinin to be PXR-dependent. An electrophoretic-mobility shift assay (EMSA) showed that artemisinin activates the DNA-binding capacity of the PXR for the CYP3A4 element. These results indicate that the induction of CYP3A4 by artemisinin is mediated through the activation of PXR. Using animal models, it was demonstrated that artemisinin abrogates dextran sulfate sodium (DDS)-induced intestinal inflammation. Preadministration of artemisinin ameliorated the clinical hallmarks of colitis in DSS-treated mice as determined by body weight loss and assessment of diarrhea, rectal bleeding, colon length, and histology. Artemisinin was found to prevent or reduce the severity of colonic inflammation by inducing CYP3A expression by activation of PXR.European Journal of Pharmacology 05/2014; 738. DOI:10.1016/j.ejphar.2014.04.050 · 2.68 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor that mediates many of the biological and toxicological actions of structurally diverse chemicals. In this study, we examined the ability of a series of ginsenosides extracted from ginseng, a traditional Chinese medicine, to bind to and activate/inhibit the AHR and AHR signal transduction. Utilizing a combination of ligand and DNA binding assays, molecular docking and reporter gene analysis, we demonstrated the ability of selected ginsenosides to directly bind to and activate the guinea pig cytosolic AHR, and to stimulate/inhibit AHR-dependent luciferase gene expression in a recombinant guinea pig cell line. Comparative studies revealed significant species differences in the ability of ginsenosides to stimulate AHR-dependent gene expression in guinea pig, rat, mouse and human cell lines. Not only did selected ginsenosides preferentially activate the AHR from one species and not others, mouse cell line was also significantly less responsive to these chemicals than rat and guinea pig cell lines, but the endogenous gene CYP1A1 could still be inducted in mouse cell line. Overall, the ability of these compounds to stimulate AHR signal transduction demonstrated that these ginsenosides are a new class of naturally occurring AHR agonists.PLoS ONE 06/2013; 8(6):e66258. DOI:10.1371/journal.pone.0066258 · 3.53 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Over the past several decades, the pharmacological effects of ginsenosides in Panax ginseng roots have been extensively investigated. Here, we developed a method for producing specific ginsenosides (F1 and F2) with good yields (F1:162 mg/g, F2:305 mg/g) using β-glycosidase purified from Aspergillus niger. In addition, each ginsenoside (at least 25 species) was separated and purified by high performance liquid chromatography (HPLC) using five different types of solvents and different purification steps. In addition, the Rg3:Rh2 mixture (1:1, w/w) was shown to inhibit a specific lung cancer cell line (NCI-H232) in vivo, displaying an anticancer effect at a dose lower than achieved using treatments with single Rg3 or Rh2. This finding suggests that the combination of ginsenosides for targeting anticancer is more effective than the use of a single ginsenoside from ginseng or red ginseng.Biotechnology and Bioprocess Engineering 06/2012; 17(3). DOI:10.1007/s12257-011-0678-2 · 1.22 Impact Factor