Inhibitory effects of polyphenols on human cytochrome P450 3A4 and 2C9 activity

Kimura, Yuka; Ito, Hideyuki; Ohnishi, Ryoko; Hatano, Tsutomu

doi:10.1016/j.fct.2009.10.041

Cited by 194 publications

(169 citation statements)

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“…Nguyen et al (2003) reported that apigenin significantly increased the cellular accumulation of vinblastine, a P-gp substrate in Panc-1 cells. Ho et al (2001) reported very weak inhibitory effect of apigenin on CYP3A4 mediated metabolism but others recently reported a potent inhibitory effect of apigenin against CYP3A4 activity (Kimura et al, 2010). Therefore, the effect of apigenin on the inhibition of CYP enzyme activity is inconclusive.…”

Section: Introductionmentioning

confidence: 89%

The Promotive Effects of Antioxidative Apigenin on the Bioavailability of Paclitaxel for Oral Delivery in Rats

Choi¹

2010

Biomolecules and Therapeutics

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-This study was to investigate the effect of apigenin on the bioavailability of paclitaxel after oral and intravenous administration in rats. The effect of apigenin on P-glycoprotein (P-gp), cytochrome P450 (CYP)3A4 activity was evaluated. The pharmacokinetic parameters of paclitaxel were determined in rats after oral (40 mg/kg) or intravenous (5 mg/kg) administration of paclitaxel with apigenin (0.4, 2 and 8 mg/kg) to rats. Apigenin inhibited CYP3A4 activity with 50% inhibition concentration (IC50) of 1.8 μM. In addition, apigenin significantly inhibited P-gp activity. Compared to the control group, apigenin significantly increased the area under the plasma concentration-time curve (AUC, p＜0.05 by 2 mg/kg, 59.0% higher; p＜0.01 by 8 mg/kg, 87% higher) of oral paclitaxel. Apigenin also significantly (p＜0.05 by 2 mg/kg, 37.2% higher; p＜0.01 by 8 mg/kg, 59.3% higher) increased the peak plasma concentration (C max ) of oral paclitaxel. Apigenin significantly increased the terminal half-life (t1/2, p＜0.05 by 8 mg/kg, 34.5%) of oral paclitaxel. Consequently, the absolute bioavailability (A.B.) of paclitaxel was significantly (p＜0.05 by 2 mg/kg, p＜0.01 by 8 mg/kg) increased by apigenin compared to that in the control group, and the relative bioavailability (R.B.) of oral paclitaxel was increased by 1.14-to 1.87-fold. The pharmacokinetics of intravenous paclitaxel were not affected by the concurrent use of apigenin in contrast to the oral administration of paclitaxel. Accordingly, the enhanced oral bioavailability by apigenin may be mainly due to increased intestinal absorption caused via P-gp inhibition by apigenin rather than to reduced renal and hepatic elimination of paclitaxel. The increase in the oral bioavailability might be mainly attributed to enhanced absorption in the gastrointestinal tract via the inhibition of P-gp and reduced first-pass metabolism of paclitaxel via the inhibition of the CYP3A subfamily in the small intestine and/or in the liver by apigenin. It appears that the development of oral paclitaxel preparations as a combination therapy is possible, which will be more convenient than the i.v. dosage form.

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Section: Introductionmentioning

confidence: 89%

The Promotive Effects of Antioxidative Apigenin on the Bioavailability of Paclitaxel for Oral Delivery in Rats

Choi¹

2010

Biomolecules and Therapeutics

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“…Synthetic antioxidants may result in liver swelling and influence liver enzyme activities (Yoshihara et al, 2010). Therefore, considering these reports and the present trends towards naturally preserved food products, herbs and spices have been targeted as sources of natural antioxidants (Kimura et al, 2010;Brewer, 2011). The use of these plant materials as natural antioxidants for food, cosmetics and other application becomes necessary because of food safety issues: (1) safety, since they are part of food man has been eating for thousands of years *Corresponding author.…”

Section: Introductionmentioning

confidence: 99%

Extraction, fractionation and assessment of antioxidant activities of active components of Aframomum sceptrum seeds

Okwuchi¹

2015

Afr. J. Biochem. Res.

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A simple procedure of extraction, fractionation and assessment of organoleptic and antioxidant properties of Aframomum sceptrum seeds was carried out, and the results were compared with a currently used synthetic antioxidant, butylated hydroxy toluene (BHT). Extraction was carried out using Soxhlet extractor and fractionation of the ethanolic extract was accomplished using vacuum liquid chromatography (VLC). Various fractions of the ethanolic extract were obtained but similar fractions were pooled together to yield six fractions (F1-F6) as guided by thin layer chromatography (TLC) analysis. Fractions obtained were subjected to sensory, chemical, spectroscopic and storage assessment in order to evaluate their antioxidant potentials. Sensory characterization and antioxidant storage tests showed that fractions F4 and F5 had non-bitter taste and yellow colour in contrast to bitter taste and dark brown colour of the crude extract. Statistical analysis (P= 0.05) showed that the antioxidant effectiveness (AE) of the fractionated extracts F4 and F5 were 62.57 and 59.13% for groundnut oil and 64.50 and 62.91% for red palm oil, respectively, and compared favourably with the standard synthetic antioxidant used. The fractions can be used to extend the shelf life of food products.

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“…These biological activities are reported to vary with the number and substitution positions of hydroxyl and/or methoxy groups in the flavonoid molecules (124)(125)(126). Inhibition of P450 enzymes by diverse flavonoid erivatives has been extensively studied in several laboratories (127)(128)(129)(130)(131)(132)(133)(134)(135)(136)(137).…”

Section: Inhibition Of P450 Enzymes By Flavonoid Derivativesmentioning

confidence: 99%

Inhibition of Carcinogen-Activating Cytochrome P450 Enzymes by Xenobiotic Chemicals in Relation to Antimutagenicity and Anticarcinogenicity

Shimada

2017

ToxicolRes

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A variety of xenobiotic chemicals, such as polycyclic aromatic hydrocarbons (PAHs), aryl-and heterocyclic amines and tobacco related nitrosamines, are ubiquitous environmental carcinogens and are required to be activated to chemically reactive metabolites by xenobiotic-metabolizing enzymes, including cytochrome P450 (P450 or CYP), in order to initiate cell transformation. Of various human P450 enzymes determined to date, CYP1A1, 1A2, 1B1, 2A13, 2A6, 2E1, and 3A4 are reported to play critical roles in the bioactivation of these carcinogenic chemicals. In vivo studies have shown that disruption of Cyp1b1 and Cyp2a5 genes in mice resulted in suppression of tumor formation caused by 7,12-dimethylbenz[a]anthracene and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, respectively. In addition, specific inhibitors for CYP1 and 2A enzymes are able to suppress tumor formation caused by several carcinogens in experimental animals in vivo, when these inhibitors are applied before or just after the administration of carcinogens. In this review, we describe recent progress, including our own studies done during past decade, on the nature of inhibitors of human CYP1 and CYP2A enzymes that have been shown to activate carcinogenic PAHs and tobacco-related nitrosamines, respectively, in humans. The inhibitors considered here include a variety of carcinogenic and/or non-carcinogenic PAHs and acethylenic PAHs, many flavonoid derivatives, derivatives of naphthalene, phenanthrene, biphenyl, and pyrene and chemopreventive organoselenium compounds, such as benzyl selenocyanate and benzyl selenocyanate; o-XSC, 1,2-, 1,3-, and 1,4-phenylenebis(methylene)selenocyanate.

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Inhibitory effects of polyphenols on human cytochrome P450 3A4 and 2C9 activity

Cited by 194 publications

References 23 publications

The Promotive Effects of Antioxidative Apigenin on the Bioavailability of Paclitaxel for Oral Delivery in Rats

The Promotive Effects of Antioxidative Apigenin on the Bioavailability of Paclitaxel for Oral Delivery in Rats

Extraction, fractionation and assessment of antioxidant activities of active components of Aframomum sceptrum seeds

Inhibition of Carcinogen-Activating Cytochrome P450 Enzymes by Xenobiotic Chemicals in Relation to Antimutagenicity and Anticarcinogenicity

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