title: [Effect of 18alpha-glycyrrhizic acid and 18beta-glycyrrhizic acid on P-gp function and expression in Caco-2 cells].
abstract: OBJECTIVE
  The aim of the present study was to evaluate the modulating effect of glycyrrhizic acid C-18 epimers, 18alpha-glycyrrhizic acid (alpha-GL) and 18beta-glycyrrhizic acid (beta-GL) on both P-glycoprotein (P-gp) activity and expression in Caco-2 cell.
  
  
  METHODS
  The effects of P-gp activity were analyzed by rhodamine (Rhd 123) accumulation test, and those of P-gp expression were analyzed by flow cytometry and real-time PCR.
  
  
  RESULTS
  At middle and high concentrations (10, 60 micromol x L(-1)), alpha-GL inhibited the function of P-gp and with on dose dependent while beta-GL induced the function of P-gp at three test concentrations with no dose dependent too. At middle and high concentrations (10, 60 micromol x L(-1)), alpha-GL down-regulated the expression of MDR1 mRNA. At high concentrations (60 micromol x L(-1)), beta-GL up-regulated the expression of MDR1 mRNA; At high concentrations (60 micromol x L(-1)), beta-GL induced the expression of P-gp protein while alpha-GL has no effect on the expression of P-gp protein at three test concentrations.
  
  
  CONCLUSIONS
  The effects of alpha-GL and beta-GL on the expression of MDR1 mRNA and CYP3A mRNA showed the same trend. The character that epimers of GL act on CYP3A and P-gp show similar stereo selectivity whether relate to PXR need further study.
authors: Clinical Pharmacy & Pharmacology Institute, Second Xiangya Hospital, Central South University, Changsha 410011, China. yan.miao@126.com
authors: Miao
authors: M
authors: Yan
authors: Lanfang
authors: L
authors: Li
authors: Huande
authors: H
authors: Li
authors: Pingfei
authors: P
authors: Fang
authors: Ping
authors: P
authors: Xu
authors: Mei
authors: M
authors: Zheng
authors: Danhua
authors: D
authors: Xu
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics* / Q000378:metabolism*; D018938:Caco-2 Cells; D015536:Down-Regulation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D019695:Glycyrrhizic Acid / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D004365:Drugs, Chinese Herbal; D019695:Glycyrrhizic Acid