Feeding of Ginkgo biloba extract (GBE) enhances gene expression of hepatic cytochrome P-450 and attenuates the hypotensive effect of nicardipine in rats.
Ginkgo biloba extract (GBE) has been used clinically for improving peripheral vascular diseases in France and Germany and is ingested widely as a herbal medicine in some countries. However, accurate information about its safety as an herbal medicine has not been sufficiently established. To address this issue, we examined the effect of GBE on hepatic drug metabolizing enzymes and their influence on hypotensive drug in rats. Male rats were fed either a control diet or diet containing GBE (0.5% w/w) for 4 weeks. The feeding of a GBE diet did not change the serum transaminase activity, but increased the liver weight and the phospholipid concentration in the liver. In addition, the GBE diet markedly increased the content of cytochrome P-450 (CYP), and the activity of glutathione S-transferase in the liver. Furthermore, the GBE diet markedly induced levels of CYP2B1/2, CYP3A1 and CYP3A2 mRNA in the liver. The levels of CYP1A1, CYP1A2, CYP2E1, CYP2C11 and CYP4A1 were unchanged. The feeding of GBE for 4 weeks significantly reduced the hypotensive effect of nicardipine that was reported to be metabolized by CYP3A2 in rats. These findings suggest that GBE reduces the therapeutic potency of the Ca2+ channel blocker, nicardipine, via enhancement of cytochrome P-450 expression.
Shinozuka
Kazumasa
K
Department of Pharmacology, School of Pharmaceutical Sciences, Mukogawa Women s Univ., Nishinomiya, Japan. kazumasa@mwu.mukogawa-u.ac.jp
Umegaki
Keizo
K
Kubota
Yoko
Y
Tanaka
Naoko
N
Mizuno
Hideya
H
Yamauchi
Jun
J
Nakamura
Kazuki
K
Kunitomo
Masaru
M
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D004032:Diet; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D015870:Gene Expression / Q000187:drug effects*; D020441:Ginkgo biloba; D005982:Glutathione Transferase / Q000378:metabolism; D007022:Hypotension / Q000201:enzymology / Q000517:prevention & control*; D007527:Isoenzymes / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D009529:Nicardipine / Q000627:therapeutic use*; D010936:Plant Extracts / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000096983:Ginkgo Extract
D002118:Calcium; D002121:Calcium Channel Blockers; D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase; D007527:Isoenzymes; D009529:Nicardipine; D010936:Plant Extracts; D012333:RNA, Messenger; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract