Inhibitory effects of polyphenols and their colonic metabolites on CYP2D6 enzyme using two different substrates

Fliszár-Nyúl, Eszter; Mohos, Violetta; Csepregi, Rita; Mladěnka, Přemysl; Poór, Miklós

doi:10.1016/j.biopha.2020.110732

Cited by 8 publications

(4 citation statements)

References 64 publications

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“…Polyphenols from Rhus verniciflua show inhibitory activity of AKR 1B10 from humans [ 29 ]. Plant polyphenols inhibit human cytochrome P450, another detoxifying enzyme [ 30 ]. AKR2E8 reduced benzaldehyde, hexanal, heptanal, nonanal, trans-2-nonenal, and citral present in mulberry leaves.…”

Section: Discussionmentioning

confidence: 99%

Novel silkworm (Bombyx mori) sulfotransferase swSULT ST3 is involved in metabolism of polyphenols from mulberry leaves

et al. 2022

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Polyphenols in plants are important for defense responses against microorganisms, insect herbivory, and control of feeding. Owing to their antioxidant, anti-cancer, and anti-inflammatory activities, their importance in human nutrition has been acknowledged. However, metabolism of polyphenols derived from mulberry leaves in silkworms (Bombyx mori) remains unclear. Sulfotransferases (SULT) are involved in the metabolism of xenobiotics and endogenous compounds. The purpose of this study is to investigate the metabolic mechanism of polyphenols mediated by B. mori SULT. Here, we identified a novel SULT in silkworms (herein, swSULT ST3). Recombinant swSULT ST3 overexpressed in Escherichia coli effectively sulfated polyphenols present in mulberry leaves. swSULT ST3 showed high specific activity toward genistein among the polyphenols. Genistein-7-sulfate was produced by the activity of swSULT ST3. Higher expression of swSULT ST3 mRNA was observed in the midgut and fat body than in the hemocytes, testis, ovary, and silk gland. Polyphenols inhibited the aldo-keto reductase detoxification of reactive aldehydes from mulberry leaves, and the most noticeable inhibition was observed with genistein. Our results suggest that swSULT ST3 plays a role in the detoxification of polyphenols, including genistein, and contributes to the effects of aldo-keto reductase in the midgut of silkworms. This study provides new insight into the functions of SULTs and the molecular mechanism responsible for host plant selection in lepidopteran insects.

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Section: Discussionmentioning

confidence: 99%

Novel silkworm (Bombyx mori) sulfotransferase swSULT ST3 is involved in metabolism of polyphenols from mulberry leaves

et al. 2022

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“…Other polyphenols (chrysin, quercetin, myricetin, acacetin, isorhamnetin, pinocembrin, tangeretin, naringenin, luteolin, diosmetin, fisetin, baicalein, kaempferol, resveratrol, bergamottin, chlorogenic acid, etc.) and their conjugated metabolites have also exhibited the ability to potently inhibit the catalytic activity of hepatic or intestinal cytochrome P450 enzymes (Fliszar‐Nyul et al., 2020; Mohos, Fliszar‐Nyul, Ungvari, Bakos, et al., 2020; Ostlund et al., 2017; Santes‐Palacios et al., 2020; Saric Mustapic et al., 2018).…”

Section: Current Strategies For Improving Bioavailability Of Nutraceu...mentioning

confidence: 99%

A review of recent progress in improving the bioavailability of nutraceutical‐loaded emulsions after oral intake

Chen

Liu

et al. 2022

Comp Rev Food Sci Food Safe

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Increasing awareness of the health benefits of specific constituents in fruits, vegetables, cereals, and other whole foods has sparked a broader interest in the potential health benefits of nutraceuticals. Many nutraceuticals are hydrophobic substances, which means they must be encapsulated in colloidal delivery systems. Oil‐in‐water emulsions are one of the most widely used delivery systems for improving the bioavailability and bioactivity of these nutraceuticals. The composition and structure of emulsions can be designed to improve the water dispersibility, physicochemical stability, and bioavailability of the encapsulated nutraceuticals. The nature of the emulsion used influences the interfacial area and properties of the nutraceutical‐loaded oil droplets in the gastrointestinal tract, which influences their digestion, as well as the bioaccessibility, metabolism, and absorption of the nutraceuticals. In this article, we review recent in vitro and in vivo studies on the utilization of emulsions to improve the bioavailability of nutraceuticals. The findings from this review should facilitate the design of more efficacious nutraceutical‐loaded emulsions with increased bioactivity.

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“…CYP enzymes and some proteins having pharmacokinetic significance may interact with a variety of natural compounds during metabolic transformation and this causes food–drug interactions 16 . There are reports dealing with the interactions of some flavonoids with biotransformation including CYP enzymes 17,18 .…”

Section: Introductionmentioning

confidence: 99%

“…15 CYP enzymes and some proteins having pharmacokinetic significance may interact with a variety of natural compounds during metabolic transformation and this causes food-drug interactions. 16 There are reports dealing with the interactions of some flavonoids with biotransformation including CYP enzymes. 17,18 The significance of the CYP2D6 enzyme in metabolism was identified by the United States Food and Drug Administration (FDA), therefore the need for extensive and detailed studies in this field has also been implied.…”

Section: Introductionmentioning

confidence: 99%

The analysis of methylxanthine fractions obtained from Camellia sinensis cultivated in Turkey and effects on the in vitro inhibition of CYP2D6 enzyme

Attar

Yapaöz

2022

Biotech and App Biochem

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Tea is a worldwide consumed herbal beverage and it was aimed in this study to reveal the major fractions of green and black tea in order to enlighten the in vitro inhibition potency on the well-known drug metabolizing enzyme CYP2D6 activity. Methylxanthine fractions were extracted from green and black tea and a yield of 0.265 g (1.06%) for 25 g of dried black tea and 0.302 g (1.2%) for 25 g of green tea was calculated. High-performance liquid chromatography analysis represented that the major components of the methylxanthine fractions were caffeine, theobromine, and theophylline. Methylxanthine content of black tea was 368.25 ± 4.6 μg/ml caffeine, 89.30 ± 2.3 μg/ml theobromine, and 3.40 ± 0.5 μg/ml theophylline, whereas that of green tea was 176.50 ± 3.7 μg/ml caffeine, 53.85 ± 1.4 μg/ml theobromine, and 2.06 ± 0.7 μg/ml theophylline. The results of concentration-dependent inhibition studies were 76% green tea, 75% black tea, and 55% caffeine at concentration of 10 mg/ml. The inhibition rates of green and black tea on CYP2D6 activity were 76% and 75%, respectively, where that of quinidine, the well-known inhibitor of CYP2D6, was 82%. Our results indicate that green and black tea is very likely to modify the CYP2D6 enzyme activity.

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Inhibitory effects of polyphenols and their colonic metabolites on CYP2D6 enzyme using two different substrates

Cited by 8 publications

References 64 publications

Novel silkworm (Bombyx mori) sulfotransferase swSULT ST3 is involved in metabolism of polyphenols from mulberry leaves

Novel silkworm (Bombyx mori) sulfotransferase swSULT ST3 is involved in metabolism of polyphenols from mulberry leaves

A review of recent progress in improving the bioavailability of nutraceutical‐loaded emulsions after oral intake

The analysis of methylxanthine fractions obtained from Camellia sinensis cultivated in Turkey and effects on the in vitro inhibition of CYP2D6 enzyme

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