Inhibition of human cytochromes P450 by components of Ginkgo biloba

Abstract

The extraction, isolation and characterization of 29 natural products contained in Ginkgo biloba have been described, which we have now tested for their in-vitro capacity to inhibit the five major human cytochrome P450 (CYP) isoforms in human liver microsomes. Weak or negligible inhibitory activity was found for the terpene trilactones (ginkgolides A, B, C and J, and bilobalide), and the flavonol glycosides. However 50% inhibitory activity (IC50) was found at concentrations less than 10 microg L(-1) for the flavonol aglycones (kaempferol, quercetin, apigenin, myricetin, tamarixetin) with CYP1A2 and CYP3A. Quercetin, the biflavone amentoflavone, sesamin, as well as (Z,Z)-4,4'-(1,4-pentadiene-1,5-diyl)diphenol and 3-nonadec-8-enyl-benzene-1,2-diol, were also inhibitors of CYP2C9. The IC50 of amentoflavone for CYP2C9 was 0.019 microg mL(-1) (0.035 microM). Thus, the principal components of Ginkgo biloba preparations in clinical use (terpene trilactones and flavonol glycosides) do not significantly inhibit these human CYPs in-vitro. However, flavonol aglycones, the biflavonol amentoflavone and several other non-glycosidic constituents are significant in-vitro inhibitors of CYP. The clinical importance of these potential inhibitors will depend on their amounts in ginkgo preparations sold to the public, and the extent to which their bioavailability allows them to reach the CYP enzymes in-situ.

The Structure-Activity Correlation on the Inhibitory Effects of Flavonoids on Cytochrome P450 3A Activity

“…6) We showed that the inhibitory effect on CYP3A activity of rutin was significantly weaker than those of quercetin, its aglycon (data not shown). In addition, though the portal serum from rats after oral ingestion of Propolis, which contains many flavonoid aglycones, strongly inhibited the activity of CYP3A, the ingestion of flavonoid-glycoside rich Passion Flower etc.…”

Effects of Pomegranate Juice on Human Cytochrome P450 2C9 and Tolbutamide Pharmacokinetics in Rats

“…Although grape juice, tea, cranberry juice, and a number of natural compounds present in Ginkgo biloba impaired CYP2C9 activity in vitro, these beverages and compounds did not altered CYP2C9-mediated clearance of flurbiprofen in humans (von Moltke et al, 2004;Greenblatt et al, 2006a,b). Furthermore, Eagling et al (1998) reported that caution must be exercised when extrapolating the effects of inhibitors from rats to humans.…”

Effects of Schisandra sphenanthera extract on the pharmacokinetics of midazolam in healthy volunteers

“…In addition to interactions between synthetic drugs, drug-herbal medicine or supplement interactions have also been observed [14]. Some reported studies on herbaldrug interactions have revealed that the extract of herbal supplements including ginkgo leaf, echinacea, and milkthistle inhibited CYP3A4 activity in human liver microsomes [15][16][17]. Interaction between SchE and tacrolimus has been reported in our previous study [9].…”