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Article: Salvianolic acid B modulates the expression of drug-metabolizing enzymes in HepG2 cells

TitleSalvianolic acid B modulates the expression of drug-metabolizing enzymes in HepG2 cells
Authors
KeywordsCYP1A2
CYP3A4
Drug metabolizing enzymes
Glutathione S-transferases
HepG2 cells
Salvianolic acid B
Issue Date2011
PublisherThe First Affiliated Hospital, Zhejiang University School of Medicine. The Journal's web site is located at http://www.hbpdint.com/
Citation
Hepatobiliary And Pancreatic Diseases International, 2011, v. 10 n. 5, p. 502-508 How to Cite?
AbstractBACKGROUND: 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. © 2011, Hepatobiliary Pancreat Dis Int.
Persistent Identifierhttp://hdl.handle.net/10722/140887
ISSN
2015 Impact Factor: 1.724
2015 SCImago Journal Rankings: 0.717
ISI Accession Number ID
Funding AgencyGrant Number
National Natural Science Foundation of China30901943
Program for New Century Excellent Talents in UniversityNCET-04-0437
E-institute of Shanghai Municipal Education CommissionE03008
Innovative Research Team in Universities of Shanghai Municipal Education Commission
Funding Information:

This work was supported by grants from the National Natural Science Foundation of China (30901943), the Program for New Century Excellent Talents in University (NCET-04-0437), the E-institute of Shanghai Municipal Education Commission (E03008) and the Innovative Research Team in Universities of Shanghai Municipal Education Commission.

References

 

DC FieldValueLanguage
dc.contributor.authorWang, QLen_HK
dc.contributor.authorWu, Qen_HK
dc.contributor.authorTao, YYen_HK
dc.contributor.authorLiu, CHen_HK
dc.contributor.authorElNezami, Hen_HK
dc.date.accessioned2011-09-23T06:20:58Z-
dc.date.available2011-09-23T06:20:58Z-
dc.date.issued2011en_HK
dc.identifier.citationHepatobiliary And Pancreatic Diseases International, 2011, v. 10 n. 5, p. 502-508en_HK
dc.identifier.issn1499-3872en_HK
dc.identifier.urihttp://hdl.handle.net/10722/140887-
dc.description.abstractBACKGROUND: 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. © 2011, Hepatobiliary Pancreat Dis Int.en_HK
dc.languageengen_US
dc.publisherThe First Affiliated Hospital, Zhejiang University School of Medicine. The Journal's web site is located at http://www.hbpdint.com/en_HK
dc.relation.ispartofHepatobiliary and Pancreatic Diseases Internationalen_HK
dc.subjectCYP1A2en_HK
dc.subjectCYP3A4en_HK
dc.subjectDrug metabolizing enzymesen_HK
dc.subjectGlutathione S-transferasesen_HK
dc.subjectHepG2 cellsen_HK
dc.subjectSalvianolic acid Ben_HK
dc.subject.meshBenzofurans - pharmacology-
dc.subject.meshCytochrome P-450 CYP1A2 - biosynthesis - genetics-
dc.subject.meshCytochrome P-450 CYP3A - biosynthesis - genetics-
dc.subject.meshGlutathione Transferase - biosynthesis-
dc.subject.meshLiver Neoplasms - enzymology - genetics - pathology-
dc.titleSalvianolic acid B modulates the expression of drug-metabolizing enzymes in HepG2 cellsen_HK
dc.typeArticleen_HK
dc.identifier.emailElNezami, H: elnezami@hkucc.hku.hken_HK
dc.identifier.authorityElNezami, H=rp00694en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/S1499-3872(11)60085-4en_HK
dc.identifier.pmid21947724-
dc.identifier.scopuseid_2-s2.0-80053209620en_HK
dc.identifier.hkuros194010en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-80053209620&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume10en_HK
dc.identifier.issue5en_HK
dc.identifier.spage502en_HK
dc.identifier.epage508en_HK
dc.identifier.isiWOS:000295148900007-
dc.publisher.placeChinaen_HK
dc.identifier.scopusauthoridWang, QL=35785535100en_HK
dc.identifier.scopusauthoridWu, Q=36801000100en_HK
dc.identifier.scopusauthoridTao, YY=24588217500en_HK
dc.identifier.scopusauthoridLiu, CH=36063265000en_HK
dc.identifier.scopusauthoridElNezami, H=6603690577en_HK

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