Induction of cyp3a in primary cultures of human hepatocytes by ginkgolides a and B.
1. The present study was designed to determine the effects of ginkgolide A, ginkgolide B and quercetin on CYP3A protein expression and enzyme activity in primary cultures of human hepatocytes. 2. Hepatocytes were pretreated with ginkgolide A, ginkgolide B and quercetin (at 1, 3, 10 and 30 micromol/L) for 48 h and then exposed to testosterone (250 micromol/L) for 30 min. Rifampin (10 micromol/L) and phenobarbital (2 mmol/L) were used as positive controls. The CYP3A activity was measured by the amount of 6beta-hydroxytestosterone in the culture medium and CYP3A protein in hepatocyte lysate was semiquantified by immunoblotting. 3. Compared with the vehicle control, ginkgolides A and B, at 30 micromol/L, significantly induced CYP3A protein expression (2.1- and 2-fold, respectively; both P < 0.01) and markedly induced CYP3A-mediated testosterone 6beta-hydroxylation (2.5-fold each; P < 0.05 for ginkgolide A; P > 0.05 for ginkgolide B). Quercetin had no apparent induction. 4. Ginkgolide A and ginkgolide B can induce CYP3A protein expression and enzyme activity in primary cultures of human hepatocytes at higher doses.
He
Nu
N
Department of Pharmacology and Toxicology, Morehouse School of Medicine, Atlanta, GA 30310, USA. nhe@msm.edu
Cai
Hong-Bo
HB
Xie
Hong-Guang
HG
Collins
Xavior
X
Edeki
Timi I
TI
Strom
Stephen C
SC
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D002478:Cells, Cultured; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D046934:Ginkgolides / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology; D041743:Herb-Drug Interactions; D006801:Humans; D006900:Hydroxylation; D007783:Lactones / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010634:Phenobarbital / Q000494:pharmacology; D011794:Quercetin / Q000494:pharmacology; D012293:Rifampin / Q000494:pharmacology; D013739:Testosterone / Q000378:metabolism
D004365:Drugs, Chinese Herbal; D046934:Ginkgolides; D007783:Lactones; D013739:Testosterone; D003577:Cytochrome P-450 Enzyme System; D011794:Quercetin; C045856:ginkgolide B; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C477042:ginkgolide A; D012293:Rifampin; D010634:Phenobarbital