The inhibition by flavonoids of 2-amino-3-methylimidazo[4,5-f]quinoline metabolic activation to a mutagen: a structure–activity relationship study

Edenharder, R.; Rauscher, R.; Platt, Karl L.

doi:10.1016/s0027-5107(97)00085-7

Cited by 62 publications

(41 citation statements)

References 31 publications

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“…Indeed, a number of¯avonoids have been shown to inhibit the N-oxidation of IQ to its corresponding hydroxylamine. 18 In the current study, at the same concentrations at which the antimutagenic activity was evident, both the oligomeric and polymeric procyanidins inhibited the O-dealkylation of methoxy-and ethoxyresoru®n, selective substrates for CYP1A2 and A1 respectively. 34 It is also possible that the procyanidins may exert, at least partly, their antigenotoxic effects by scavenging the metabolically generated reactive intermediates.…”

Section: Discussionsupporting

confidence: 47%

“…A number of polyphenolics suppressed the mutagenicity of chemical carcinogens, largely by inhibiting their bioactivation. 17,18 Indeed, all three mechanisms have been implicated in the antimutagenic activity of aqueous tea infusions, 19,20 although the¯avanols, the major polyphenolics in tea, are unlikely to be responsible for these effects. 16,21 All emphasis, however, has been placed on monomeric polyphenolics, and the role of higher-molecularweight compounds, also present in substantial amounts in plant material, 22,23 has been largely ignored.…”

Section: ±3mentioning

confidence: 99%

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Modulation of the mutagenicity of food carcinogens by oligomeric and polymeric procyanidins isolated from grape seeds: synergistic genotoxicity withN-nitrosopyrrolidine

Catterall¹,

Souquet²,

Cheynier³

et al. 2000

J. Sci. Food Agric.

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Section: Discussionsupporting

confidence: 47%

Section: ±3mentioning

confidence: 99%

Modulation of the mutagenicity of food carcinogens by oligomeric and polymeric procyanidins isolated from grape seeds: synergistic genotoxicity withN-nitrosopyrrolidine

Catterall¹,

Souquet²,

Cheynier³

et al. 2000

J. Sci. Food Agric.

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“…Our results suggest that silibinin may be useful in further characterising human CYP3A enzymes. Indeed, structure-activity relationships of flavonoids with respect to effects on other cytochrome P450 enzymes have been established (Siess et al 1995;Edenharder et al 1997;Lee et al 1998), but these data have not yet been used to obtain information on the binding site characteristics of the enzymes.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory Effects of Silibinin on Cytochrome P‐450 Enzymes in Human Liver Microsomes

Beckmann-Knopp¹,

Rietbrock²,

Weyhenmeyer³

et al. 2000

Pharmacology & Toxicology

129

101

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Silibinin, the main constituent of silymarin, a flavonoid drug from silybum marianum used in liver disease, was tested for inhibition of human cytochrome P-450 enzymes. Metabolic activities were determined in liver microsomes from two donors using selective substrates. With each substrate, incubations were carried out with and without silibinin (concentrations 3.7-300 mM) at 37ae in 0.1 M KH 2 PO 4 buffer containing up to 3% DMSO. Metabolite concentrations were determined by HPLC or direct spectroscopy. First, silibinin IC 50 values were determined for each substrate at respective K M concentrations. Silibinin had little effect (IC 50 Ͼ200 mM) on the metabolism of erythromycin (CYP3A4), chlorzoxazone (CYP2E1), S(π)-mephenytoin (CYP2C19), caffeine (CYP1A2) or coumarin (CYP2A6). A moderate effect was observed for high affinity dextromethorphan metabolism (CYP2D6) in one of the microsomes samples tested only (IC 50 Ω173 mM). Clear inhibition was found for denitronifedipine oxidation (CYP3A4; IC 50 Ω29 mM and 46 mM) and S(ª)-warfarin 7-hydroxylation (CYP2C9; IC 50 Ω43 mM and 45 mM). When additional substrate concentrations were tested to assess enzyme kinetics, silibinin was a potent competitive inhibitor of dextromethorphan metabolism at the low affinity site, which is not CYP2D6 (K i,c Ω2.3 mM and 2.4 mM). Inhibition was competitive for S(ª)-warfarin 7-hydroxylation (K i,c Ω18 mM and 19 mM) and mainly non-competitive for denitronifedipine oxidation (K i,n Ω9 mM and 12 mM). With therapeutic silibinin peak plasma concentrations of 0.6 mM and biliary concentrations up to 200 mM, metabolic interactions with xenobiotics metabolised by CYP3A4 or CYP2C9 cannot be excluded.

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“…3 The Lineweavere-Burk plots analysis of α-glucosidase (a), α-amylase (b) and pancreatic lipase (c) inhibitory effects by quercetagetin the molecule of quercetin. Edenharder et al (1997) reported that the enzyme activity could be inhibited by the flavanone and its structure, hydroxyl replaced on C6 of flavanone had a significant influence on enzyme inhibition activities. We speculated that C6-OH group weakened the inhibitory activities of quercetagetin to α-glucosidase and α-amylase.…”

Section: Abtsmentioning

confidence: 99%

In vitro antioxidant, anti-diabetic and antilipemic potentials of quercetagetin extracted from marigold (Tagetes erecta L.) inflorescence residues

Wang

Chen

et al. 2016

J Food Sci Technol

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Quercetagetin, the major flavonoid in marigold (Tagetes erecta L.) inflorescence residues was extracted and purified. The content of quercetagetin after the purification was 89.91 ± 0.26 %. The in vitro antioxidant activity of quercetagetin and its potential in controlling diabetes mellitus and obesity were investigated and compared to quercetin and rutin. The 50 % inhibitory concentration (IC 50 ) values of quercetagetin on scavenging 1, 1-diphenyl-2-picrylhydrazyl (DPPH), 2,2-azinobis-(3-ethylbenzothiazolin-6-sulfonic acid) (ABTS) and hydroxyl radicals were 27.12 ± 1.31 μmol/L, 12.16 ± 0.56 μmol/L and 1833.97 ± 6.66 μmol/L, respectively. The IC 50 values of quercetagetin on α-glucosidase, α-amylase and pancreatic lipase were 180.11 ± 3.68 μmol/L, 137.71 ± 3.55 μmol/L and 2327.58 ± 12.37 μmol/L, respectively. These results indicated that quercetagetin exhibited strong in vitro antioxidant, anti-diabetic and antilipemic activities. Lineweaver-Burk plots analysis elucidated that quercetagetin inhibited α-glucosidase and α-amylase non-competitively, while its inhibition against pancreatic lipase was involved in a mixed-type pattern. Moreover, strong correlations were found between ABTS ·+ /DPPH · scavenging activities and lipase inhibitory activity (R 2 > 0.90), as well as ·OH scavenging activity and α-amylase inhibitory activity (R 2 = 0.8967).

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The inhibition by flavonoids of 2-amino-3-methylimidazo[4,5-f]quinoline metabolic activation to a mutagen: a structure–activity relationship study

Cited by 62 publications

References 31 publications

Modulation of the mutagenicity of food carcinogens by oligomeric and polymeric procyanidins isolated from grape seeds: synergistic genotoxicity withN-nitrosopyrrolidine

Modulation of the mutagenicity of food carcinogens by oligomeric and polymeric procyanidins isolated from grape seeds: synergistic genotoxicity withN-nitrosopyrrolidine

Inhibitory Effects of Silibinin on Cytochrome P‐450 Enzymes in Human Liver Microsomes

In vitro antioxidant, anti-diabetic and antilipemic potentials of quercetagetin extracted from marigold (Tagetes erecta L.) inflorescence residues

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