Human CYP1A1 inhibition by flavonoids

Santes-Palacios, Rebeca; Marroquín-Pérez, Ana L.; Hernández-Ojeda, S.L.; Camacho-Carranza, Rafael; Govezensky, Tzipe; Espinosa-Aguirre, J.J.

doi:10.1016/j.tiv.2019.104681

Cited by 24 publications

(20 citation statements)

References 43 publications

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“…Other naturally occurring polyphenolic compounds, such as galangin (3,5,7-trihydroxyflavone) and apigenin (5,7,4-trihydroxyflavone) also inhibit CYP1A1 and CYP1A2 activities [ 49 ]. Reported values of apparent Ki for the inhibition of CYP1A1by galangin is 0.015 µM [ 50 ] and 0.32 µM apigenin [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Interaction of Thalassia testudinum Metabolites with Cytochrome P450 Enzymes and Its Effects on Benzo(a)pyrene-Induced Mutagenicity

Delgado-Roche¹,

Santes-Palacios

Herrera

et al. 2020

Marine Drugs

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The aim of the present work was to evaluate the effects of Thalassia testudinum hydroethanolic extract, its polyphenolic fraction and thalassiolin B on the activity of phase I metabolizing enzymes as well as their antimutagenic effects. Spectrofluorometric techniques were used to evaluate the effect of tested products on rat and human CYP1A and CYP2B activity. The antimutagenic effect of tested products was evaluated in benzo[a]pyrene (BP)-induced mutagenicity assay by an Ames test. Finally, the antimutagenic effect of Thalassia testudinum (100 mg/kg) was assessed in BP-induced mutagenesis in mice. The tested products significantly (p < 0.05) inhibit rat CYP1A1 activity, acting as mixed-type inhibitors of rat CYP1A1 (Ki = 54.16 ± 9.09 μg/mL, 5.96 ± 1.55 μg/mL and 3.05 ± 0.89 μg/mL, respectively). Inhibition of human CYP1A1 was also observed (Ki = 197.1 ± 63.40 μg/mL and 203.10 ± 17.29 μg/mL for the polyphenolic fraction and for thalassiolin B, respectively). In addition, the evaluated products significantly inhibit (p < 0.05) BP-induced mutagenicity in vitro. Furthermore, oral doses of Thalassia testudinum (100 mg/kg) significantly reduced (p < 0.05) the BP-induced micronuclei and oxidative damage, together with an increase of reduced glutathione, in mice. In summary, Thalassia testudinum metabolites exhibit antigenotoxic activity mediated, at least, by the inhibition of CYP1A1-mediated BP biotransformation, arresting the oxidative and mutagenic damage. Thus, the metabolites of T. testudinum may represent a potential source of chemopreventive compounds for the adjuvant therapy of cancer.

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Section: Discussionmentioning

confidence: 99%

Interaction of Thalassia testudinum Metabolites with Cytochrome P450 Enzymes and Its Effects on Benzo(a)pyrene-Induced Mutagenicity

Delgado-Roche¹,

Santes-Palacios

Herrera

et al. 2020

Marine Drugs

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“…Dietary factors such as phytochemicals affect CYP expression and activity which may be of importance in diet-drug interactions. Several studies evidenced the inhibitory properties of flavonoids by structural interference with CYP proteins [ 167 ]. Additionally, soy components seem to promiscuously modulate several nuclear receptors including AhR, PXR, PPAR and liver X receptor (LXR), altering drug pharmacokinetics and therapeutic efficacy [ 168 ] ( Figure 5 ).…”

Section: Nongenetic Factors Influencing Cytochrome P450s Expression and Activitymentioning

confidence: 99%

The Central Role of Cytochrome P450 in Xenobiotic Metabolism—A Brief Review on a Fascinating Enzyme Family

Esteves

Rueff

Kranendonk

2021

JoX

270

146

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Human Cytochrome P450 (CYP) enzymes constitute a superfamily of membrane-bound hemoproteins that are responsible for the metabolism of a wide variety of clinically, physiologically, and toxicologically important compounds. These heme-thiolate monooxygenases play a pivotal role in the detoxification of xenobiotics, participating in the metabolism of many structurally diverge compounds. This short-review is intended to provide a summary on the major roles of CYPs in Phase I xenobiotic metabolism. The manuscript is focused on eight main topics that include the most relevant aspects of past and current CYP research. Initially, (I) a general overview of the main aspects of absorption, distribution, metabolism, and excretion (ADME) of xenobiotics are presented. This is followed by (II) a background overview on major achievements in the past of the CYP research field. (III) Classification and nomenclature of CYPs is briefly reviewed, followed by (IV) a summary description on CYP’s location and function in mammals. Subsequently, (V) the physiological relevance of CYP as the cornerstone of Phase I xenobiotic metabolism is highlighted, followed by (VI) reviewing both genetic determinants and (VI) nongenetic factors in CYP function and activity. The last topic of the review (VIII) is focused on the current challenges of the CYP research field.

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“…Activated K-RAS also inhibits the degradation of ZNF304 transcription factor which is a transcriptional regulator of tumorsuppressor β1 integrin [34]. However, resveratrol [35], EGCG [36] and myricetin [37] can ameliorate these harmful effects by inhibiting the enzyme CYP1A1, which activates the procarcinogenic form of DMBA to an active carcinogen (while DMBA induce CYP1A1) [38]. This was confirmed by our results, where all tested substances significantly inhibited hypomethylation; moreover, hypermethylation was observed in the flavonoid consuming group compared to the untreated controls compared with other chemopreventive substances (Figs 1-3).…”

Section: Discussionmentioning

confidence: 99%

The effects of flavonoids, green tea polyphenols and coffee on DMBA induced LINE-1 DNA hypomethylation

et al. 2021

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The intake of carcinogenic and chemopreventive compounds are important nutritional factors related to the development of malignant tumorous diseases. Repetitive long interspersed element-1 (LINE-1) DNA methylation pattern plays a key role in both carcinogenesis and chemoprevention. In our present in vivo animal model, we examined LINE-1 DNA methylation pattern as potential biomarker in the liver, spleen and kidney of mice consuming green tea (Camellia sinensis) extract (catechins 80%), a chinese bayberry (Morella rubra) extract (myricetin 80%), a flavonoid extract (with added resveratrol) and coffee (Coffee arabica) extract. In the organs examined, carcinogen 7,12-dimethylbenz(a)anthracene (DMBA)-induced hypomethylation was prevented by all test materials except chinese bayberry extract in the kidneys. Moreover, the flavonoid extract caused significant hypermethylation in the liver compared to untreated controls and to other test materials. The tested chemopreventive substances have antioxidant, anti-inflammatory properties and regulate molecular biological signaling pathways. They increase glutathione levels, induce antioxidant enzymes, which decrease free radical damage caused by DMBA, and ultimately, they are able to increase the activity of DNA methyltransferase enzymes. Furthermore, flavonoids in the liver may inhibit the procarcinogen to carcinogen activation of DMBA through the inhibition of CYP1A1 enzyme. At the same time, paradoxically, myricetin can act as a prooxidant as a result of free radical damage, which can explain that it did not prevent hypomethylation in the kidneys. Our results demonstrated that LINE-1 DNA methylation pattern is a useful potential biomarker for detecting and monitoring carcinogenic and chemopreventive effects of dietary compounds.

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Human CYP1A1 inhibition by flavonoids

Cited by 24 publications

References 43 publications

Interaction of Thalassia testudinum Metabolites with Cytochrome P450 Enzymes and Its Effects on Benzo(a)pyrene-Induced Mutagenicity

Interaction of Thalassia testudinum Metabolites with Cytochrome P450 Enzymes and Its Effects on Benzo(a)pyrene-Induced Mutagenicity

The Central Role of Cytochrome P450 in Xenobiotic Metabolism—A Brief Review on a Fascinating Enzyme Family

The effects of flavonoids, green tea polyphenols and coffee on DMBA induced LINE-1 DNA hypomethylation

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