Effect of Ginkgo biloba extract on rat hepatic microsomal CYP1A activity: role of ginkgolides, bilobalide, and flavonols

Abstract

The present study investigated the in vitro effect of Ginkgo biloba extracts and some of the individual constituents (ginkgolides, bilobalide, and flavonols such as kaempferol, quercetin, isorhamnetin, and their glycosides) on CYP1A-mediated 7-ethoxyresorufin O-dealkylation in hepatic microsomes isolated from rats induced with beta-naphthoflavone. G. biloba extract competitively inhibited CYP1A activity, with an apparent Ki value of 1.6 +/- 0.4 microg/mL (mean +/- SE). At the concentrations present in the G. biloba extracts, ginkgolides A, B, C, and J and bilobalide did not affect CYP1A activity, whereas kaempferol (IC50 = 0.006 +/- 0.001 microg/mL, mean +/- SE), isorhamnetin (0.007 +/- 0.001 microg/mL), and quercetin (0.050 +/- 0.003 microg/mL) decreased this activity. The monoglycosides (1 and 10 microg/mL) and diglycosides (10 microg/mL) of kaempferol and quercetin but not those of isorhamnetin also inhibited CYP1A activity. The order of inhibitory potency was kaempferol approximately equal to isorhamnetin > quercetin, and for each of these flavonols the order of potency was aglycone >> monoglycoside > diglycoside. In summary, G. biloba extract competitively inhibited rat hepatic microsomal CYP1A activity, but the effect was not due to ginkgolides A, B, C, or J, bilobalide, kaempferol, quercetin, isorhamnetin, or the respective flavonol monoglycosides or diglycosides.

Rapid determination of six metabolites from multiple cytochrome P450 probe substrates in human liver microsome by liquid chromatography/mass spectrometry: application to high‐throughput inhibition screening of terpenoids

“…The monoterpene alcohols (MEN, CAM, and BOR) were reported to potently inhibit the activitities of CYP2A6 and CYP2B, but not other isoenzymes 32, 33. Although flavonols such as kaempferol, quercetin and isorhamnetin in Ginkgo biloba can inhibit the activities of CYP1A2, CYP2C9 and CYP3A4, BIO and GIN‐B do not affect the six CYP isoenzymes tested in the current study 34, 35. Bapiro et al 36.…”

LACK OF EVIDENCE FOR INDUCTION OF CYP2B1, CYP3A23, AND CYP1A2 GENE EXPRESSION BY Panax ginseng AND Panax quinquefolius EXTRACTS IN ADULT RATS AND PRIMARY CULTURES OF RAT HEPATOCYTES

“…Treatment of Animals. Adult male Sprague-Dawley rats (250 -275 g) were purchased from Charles River Canada (Montreal, QC, Canada) and housed in our animal care facility, as described previously (Kuo et al, 2004). Rats were administered P. ginseng extract (30 or 100 mg/kg) or the vehicle (0.9% NaCl) by oral gavage as a single dose or as multiple doses (once daily for 4 consecutive days).…”

“…Protein concentrations were determined using the Bio-Rad Protein Assay Kit. EROD and BROD activities were determined as described previously (Kuo et al, 2004).…”

Molecular Role of Nitric Oxide in Secondary Products Production </span> <span lang="EN-US" style="font-size: 12.0pt; font-family: 'Times New Roman',serif"> in <i>Ginkgo biloba </i>Cell Suspension Culture

“…Ginkgo trees are now widely planted in China, Japan, Korea, France, Germany and the United States for both ornamental and medicinal purposes. Kuo et al (2004) demonstrated that G. biloba extract competitively inhibited rat hepatic microsomal CYP1A-mediated enzyme activity, as determined by experiments performed on extracts containing terpene trilactones and ginkgo flavonol glycosides. Despite the fact that the plant appears to possess antioxidant activity, the mechanism of action of G. biloba is not known.…”