Biologically Active Secondary Metabolites from <i>Ginkgo biloba</i>

Bedir, Erdal; Tatli, Irem I; Khan, Riaz; Zhao, Jianping; Takamatsu, Satoshi; Walker, Larry; Goldman, Peter; Khan, Ikhlas A.

doi:10.1021/jf011682s

Cited by 78 publications

(74 citation statements)

References 22 publications

(43 reference statements)

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“…Flavonol glycosides are hydrolyzed to the corresponding aglycones by the ␤-glucosidases present in intestinal microflora, and the resulting aglycones are absorbed (Cermak and Wolffram, 2006). Kaempferol and quercetin aglycones appear to be more potent than the corresponding glycosides in various biological activities; for example, antioxidant activity (Bedir et al, 2002). In the present study, 3-O-glucoside (a monoglycoside) and 3-O-rutinoside (a diglycoside) of kaempferol, quercetin, and isorhamnetin did not affect CYP2B6 catalytic activity.…”

Section: Discussionmentioning

confidence: 59%

Inhibition of Human CYP2B6-Catalyzed Bupropion Hydroxylation by Ginkgo biloba Extract: Effect of Terpene Trilactones and Flavonols

Lau

Chang²

2009

Drug Metab Dispos

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ABSTRACT:Cytochrome P450 2B6 (CYP2B6) is expressed predominantly in human liver. It catalyzes the oxidative biotransformation of various drugs, including bupropion, which is an antidepressant and a tobacco use cessation agent. Serious adverse effects of high dosages of bupropion have been reported, including the onset of seizure. As Ginkgo biloba extract may be consumed with bupropion or another CYP2B6 drug substrate, potential exists for an herb-drug interaction. Therefore, we investigated the effect of G. biloba extract and some of its chemical constituents (terpene trilactones and flavonols) on the in vitro catalytic activity of CYP2B6 as assessed by the bupropion hydroxylation assay with recombinant enzyme and hepatic microsomes. The amount of hydroxybupropion was quantified by a novel and validated ultraperformance liquid chromatography/mass spectrometry method. Enzyme kinetic analysis indicated that G. biloba extract competitively inhibited hepatic microsomal CYP2B6-catalyzed bupropion hydroxylation (apparent K i was 162 ؎ 14 g/ml). Bilobalide and ginkgolides A, B, C, and J were not responsible for the inhibition of CYP2B6 catalytic activity by the extract. Whereas the 3-O-glucoside and 3-O-rutinoside of quercetin, kaempferol, and isorhamnetin had no effect, the corresponding aglycones (10 and 50 g/ml) decreased hepatic microsomal bupropion hydroxylation. The inhibition of CYP2B6 by kaempferol was competitive (apparent K i was 10 ؎ 1 g/ml). In summary, G. biloba extract and its flavonol aglycones are naturally occurring inhibitors of in vitro CYP2B6 catalytic activity and bupropion hydroxylation. Future studies are needed to investigate whether G. biloba extract interacts in vivo with bupropion or other clinically important CYP2B6 drug substrates.Cytochrome P450 2B6 (CYP2B6) is expressed mainly in human liver, although this enzyme has also been detected in various extrahepatic tissues (Gervot et al., 1999). Considerable variability exists not only in hepatic expression of CYP2B6 mRNA (280-fold) (Chang et al., 2003) and protein (Ͼ288-fold) (Hesse et al., 2004) but also CYP2B6 enzyme activity (80-fold) (Faucette et al., 2000). The basis for the interindividual variability may relate to pharmacogenetics (Hofmann et al., 2008) and the fact that this enzyme is subject to induction by various drugs and other chemicals in a mechanism that involves transcription factors such as the constitutive androstane receptor (Sueyoshi et al., 1999), which also exhibits large interindividual differences (240-fold) in hepatic expression (Chang et al., 2003). The magnitude of CYP2B6 catalytic activity may also be altered as a result of enzyme inhibition by various synthetic drugs (Turpeinen et al., 2004;Walsky et al., 2006); naturally occurring compounds, including phenethyl isothiocyanate (Nakajima et al., 2001), -viniferin (Piver et al., 2003, and citral ; and herbal supplements, such as Woohwangcheongsimwon , Andrographis paniculata extract (Pekthong et al., 2008), and curcuminoid extract (Volak et al., 2008). Important CYP2...

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Section: Discussionmentioning

confidence: 59%

Inhibition of Human CYP2B6-Catalyzed Bupropion Hydroxylation by Ginkgo biloba Extract: Effect of Terpene Trilactones and Flavonols

Lau

Chang²

2009

Drug Metab Dispos

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“…In the HSQC spectra, correlations appeared between the anomeric proton signal at δ 5.55 (assigned to the 1´-position of glucose) and the carbon signal at δ 95.7 for the Z isomer, and the anomeric proton signal at δ 5.52 (assigned to the 1'-position of glucose) also correlates to the carbon signal at δ 95.5 for the E isomer. The anomeric proton signal at δ 4.72 corresponds to a rhamnose unit (assigned to the 1"-position of rhamnose) and correlates to the carbon signal at δ 102.2, suggesting that the bond between the two sugars is at the position 1"-6', [16,17]. This notion has been confirmed by a Tollen´s test, since no reducing sugars were found.…”

Section: Resultsmentioning

confidence: 69%

A Novel Antioxidant Phenyl Disaccharide from Populus tremula Knotwood

et al. 2007

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Abstract:The complete characterization of two compounds obtained from the acetone extract of Populus tremula knotwood has been was achieved using LC-DAD-MS, MS/MS, IR and NMR. The new compounds were unequivocally identified as a mixture of the ester isomers of the (E) and (Z) p-coumarate of 1-O-rutinose. The isomers showed the capacity to inhibit lipid peroxidation induced by tert-butylhydroperoxide and to trap peroxyl radicals, as determined by a chemiluminescence method. These new phenyl disaccharides also showed a significant ORAC (oxygen radical absorbance capacity) value, i.e. 11.7 µM TE (Trolox Equivalents).

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“…All these compounds share a distinct structural characteristic, an 8-aryl substituent in apigenin skeleton, which has never been reported in family Selaginellaceae, and also rarely discovered from natural resources [30]. Unciflavones A (1) and B (2) have an acrylate side chain at the position of C-8″ and unciflavone C (3) possess a rare C6-C4 unit at the C-8 position of flavonoid skeleton, which are discovered for the first time.…”

Section: Resultsmentioning

confidence: 99%

Unciflavones A–F, six novel flavonoids from Selaginella uncinata (Desv.) Spring

Zou

et al. 2014

Fitoterapia

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Biologically Active Secondary Metabolites from Ginkgo biloba

Cited by 78 publications

References 22 publications

Inhibition of Human CYP2B6-Catalyzed Bupropion Hydroxylation by Ginkgo biloba Extract: Effect of Terpene Trilactones and Flavonols

Inhibition of Human CYP2B6-Catalyzed Bupropion Hydroxylation by Ginkgo biloba Extract: Effect of Terpene Trilactones and Flavonols

A Novel Antioxidant Phenyl Disaccharide from Populus tremula Knotwood

Unciflavones A–F, six novel flavonoids from Selaginella uncinata (Desv.) Spring

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