title: In vitro studies of berberine metabolism and its effect of enzyme induction on HepG2 cells.
abstract: BACKGROUND
  Berberine (BER) and BER-original herbal medicines have a variety of pharmacological functions and have been widely used in clinical. However, its effect of enzyme induction on cytochrome P450 (CYP) in human hepatocytes is unknown.
  
  
  METHODS
  Metabolism of berberine and its effect on main metabolic enzymes in HepG2 cell in vitro was investigated. Cocktail probe drugs, mRNA expression and protein expression were used to evaluate the metabolism potency. Meanwhile, an UPLC-MS/MS method was validated for the analysis of BER and four probe drugs in HepG2 cell.
  
  
  RESULTS
  BER significantly increased the metabolism of midazolam, phenacetin and tolbutamide by inducing the CYP1A2 and 3A4 enzyme in a dose-dependent manner, the mRNA and protein expression of CYP1A2 and 3A4 were increased by berberine at 1000ng·mL(-1). The activity of CYP1A2 and 3A4 could be induced by BER more than 500ng·mL(-1) in HepG2 cell, which was confirmed by the increase of its mRNA and protein expression.
  
  
  CONCLUSIONS
  BER increases the metabolism of cocktail drugs such as midazolam, phenacetin and tolbutamide by increasing the mRNA and protein expression of CYP1A2 and 3A4.
authors.affiliation: Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China. Electronic address: piaoliumu828@163.com.
authors.forename: Han-Ming
authors.initials: HM
authors.lastname: Cui
authors.affiliation: Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.
authors.forename: Qiu-Yan
authors.initials: QY
authors.lastname: Zhang
authors.affiliation: Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.
authors.forename: Jia-Long
authors.initials: JL
authors.lastname: Wang
authors.affiliation: Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.
authors.forename: Jian-Long
authors.initials: JL
authors.lastname: Chen
authors.affiliation: Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Zhang
authors.affiliation: Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China. Electronic address: xiaolintong66@sina.com.
authors.forename: Xiao-Lin
authors.initials: XL
authors.lastname: Tong
mesh_terms: D001483:Base Sequence; D001599:Berberine / Q000378:metabolism* / Q000494:pharmacology; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers; D004790:Enzyme Induction / Q000187:drug effects*; D056945:Hep G2 Cells; D006801:Humans; D066298:In Vitro Techniques; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D053719:Tandem Mass Spectrometry
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; D001599:Berberine; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A
keywords: Berberine; CYP enzyme; Drug metabolism; Drug–drug interaction; HepG2 cell; Metabolic enzyme induction