Effects of Ginkgo biloba extract and tanshinone on cytochrome P-450 isozymes and glutathione transferase in rats.
OBJECTIVE
To investigate the effects of Ginkgo biloba extract (GbE) and tanshinone (Tan) on cytochrome P450 (CYP) isozymes and glutathione transferase (GT) in rats.


METHODS
Several CYP-dependent reactions were monitored in liver and kidney microsomes of male rats treated ig with GbE and Tan daily for 10 d. The activity of GT, the levels of malondialdehyde (MDA) and nitric oxide (NO) in the tissues were also determined.


RESULTS
CYP1A1, 1A2, and 2B1 activities in the liver were all significantly increased (2-9.5 fold) by pretreatment with GbE or Tan (P<0.01). An induction (1.4 fold) of CYP 2E1 activity was observed at the higher dose of GbE treatment (P<0.01), but a reduction (1.9 fold) after Tan administration (P<0.01). Whereas GbE could induce CYP3A (1.6 fold) (P<0.01) but Tan had no effects. Furthermore, the activities of CYP 1A1 (5.6-8.9 fold) and 1A2 (2.6 fold) in the kidney were induced by GbE (P<0.01). The activity of GT in rat liver receiving Tan was significantly increased (P<0.05) and a dramatic reduction in the activity of GT in the kidney was observed in the GbE-treated group (P<0.01). In addition, the GbE treatment markedly decreased the levels of MDA and NO in the tissues of rats (P<0.01).


CONCLUSIONS
The modulation of CYP isozymes by GbE and Tan may result in altered metabolism of coadministered drugs. In addition, GbE is an active antioxidant and nitric oxide inhibitor in vivo.
Yang
Xiu-Fen
XF
Department of Clinical Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Wang
Nai-Ping
NP
Lu
Wen-Hong
WH
Zeng
Fan-Dian
FD
D045784:Abietanes; D000818:Animals; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology*; D020441:Ginkgo biloba / Q000737:chemistry; D005982:Glutathione Transferase / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008861:Microsomes / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010616:Phenanthrenes / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D045784:Abietanes; D000975:Antioxidants; D004365:Drugs, Chinese Herbal; D007527:Isoenzymes; D010616:Phenanthrenes; C021751:tanshinone; D009569:Nitric Oxide; D008315:Malondialdehyde; D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase