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Salvianolic acid B modulates the expression of drug-metabolizing enzymes in HepG2 cells |
Qing-Lan Wang, Quoc Wu, Yan-Yan Tao, Cheng-Hai Liu and Hani El-Nezami |
Shanghai, China
Author Affiliations: Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China (Wang QL, Tao YY and Liu CH); Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai 201203, China (Wang QL); School of Public Health and Clinical Nutrition, University of Kuopio, Kuopio, Finland (Wang QL, Wu Q and El-Nezami H), School of Biological Sciences, University of Hong Kong, Hong Kong SAR, China (El-Nezami H)
Corresponding Author: Cheng-Hai Liu, MD, Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China (Tel: 86-21-20256521; Email: Chenghai_liu@yahoo.com.cn) |
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Abstract BACKGROUND: Enzymes involved in drug and xenobiotic metabolism have been considered to exist in two groups: phase I and phase II enzymes. Cytochrome P450 isoenzymes (CYPs) are the most important phase I enzymes in the metabolism of xenobiotics. The products of phase I metabolism are then acted upon by phase II enzymes, including glutathione S-transferases (GSTs). Herbs that inhibit CYPs such as CYP3A4 or that induce GSTs may have the potential to protect against chemical carcinogenesis since the mutagenic effects of carcinogens are often mediated through an excess of CYP-generated reactive intermediates. This study was designed to investigate the effects of salvianolic acid B (Sal B), a pure compound extracted from Radix Salviae Miltiorrhizae, a Chinese herb, on cell proliferation and CYP1A2 and CYP3A4 mRNA expression in the presence or absence of rifampicin, a potent inducer of CYPs and GST protein expression in HepG2 cells.
METHODS: HepG2 cells were incubated with different concentrations of Sal B. Cell proliferation was determined by SYTOX-Green nucleic acid staining. CYP3A4 and CYP1A2 mRNA expression was assayed by real-time PCR. GST protein expression was analyzed by Western blotting.
RESULTS: Low concentrations of Sal B (0-20 µmol/L) had no significant effects on cell proliferation, while higher concentrations (100-250 µmol/L) significantly inhibited proliferation in a concentration-dependent manner. Ten µmol/L Sal B, but not 1 µmol/L, down-regulated CYP3A4 and CYP1A2 mRNA expression after 24 hours of incubation, whereas both 1 and 10 µmol/L Sal B down-regulated CYP3A4 mRNA expression after 96 hours of incubation; moreover, 1 and 10 µmol/L Sal B inhibited CYP3A4 mRNA expression induced by rifampicin. Both 1 µmol/L and 10 µmol/L Sal B increased GST expression.
CONCLUSION: Sal B inhibits CYP3A4 and CYP1A2 mRNA expression and induces GST expression in HepG2 cells.
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