Comprehensive Investigation of Stereoselective Food Drug Interaction Potential of Resveratrol on Nine P450 and Six UGT Isoforms in Human Liver Microsomes

Ji, Seung-Bae; Park, Soyoung; Bae, Subin; Seo, Hyung-Ju; Kim, Sin-Eun; Lee, Gyung-Min; Wu, Zhexue; Liu, Kwang-Hyeon

doi:10.3390/pharmaceutics13091419

Cited by 8 publications

(9 citation statements)

References 60 publications

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“…The inhibitory potentials of chrysophanol (IC 50 = 1.99 µM) and physcion (IC 50 = 2.16 µM) against CYP1A2 in HLMs were higher than those observed against rCYP1A2 (IC 50 = 0.29 and 0.88 µM, respectively) [16]. This could be attributed to the differences in incubation conditions, such as enzyme source (HLM versus rCYP1A2) or CYP1A2 probe substrate (phenacetin versus melatonin) [16,23]. For example, the IC 50 value of mollugin for CYP1A2-mediated POD activity in rCYP1A2 was five-fold higher than that in HLMs [27].…”

Section: Inhibition Of Cyp1a2 Activity By Five Major Phytochemicals F...mentioning

confidence: 90%

“…Electrospray ionization was performed in the positive-and negative-ion modes at 4.0 and −3.5 kV, respectively. For each metabolite, quantitation was carried out in selected reaction monitoring (SRM) mode using the following precursor-to-product ion transition: m/z 152 > 110 for acetaminophen (CYP1A2), m/z 214 > 186 for resorufin (CYP1A1 and CYP1A2), m/z 163 > 107 for 7-hydroxycoumarin (CYP2A6), m/z 256 > 238 for 6-hydroxybupropion (CYP2B6), m/z 328 > 283 for N-desethylamodiaquine (CYP2C8), m/z 287 > 89 for 5-hydroxytolbutamide (CYP2C9), m/z 362 > 214 for 4-hydroxyomeprazole (CYP2C9), m/z 258 > 157 for dextrorphan (CYP2D6), m/z 184 > 120 for 6-hydroxychlorzoxazone (CYP2E1), m/z 342 > 203 for 1 -hydroxymidazolam (CYP3A), and m/z 295 > 100 for trimipramine (IS) [23,24].…”

Section: Lc-ms/ms Analysismentioning

confidence: 99%

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Potent and Selective Inhibition of CYP1A2 Enzyme by Obtusifolin and Its Chemopreventive Effects

Park

Park²,

Durai³

et al. 2022

Pharmaceutics

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Obtusifolin, a major anthraquinone component present in the seeds of Cassia tora, exhibits several biological activities, including the amelioration of memory impairment, prevention of breast cancer metastasis, and reduction of cartilage damage in osteoarthritis. We aimed to evaluate the inhibitory effects of obtusifolin and its analogs on CYP1A enzymes, which are responsible for activating procarcinogens, and investigate its inhibitory mechanism and chemopreventive effects. P450-selective substrates were incubated with human liver microsomes (HLMs) or recombinant CYP1A1 and CYP1A2 in the presence of obtusifolin and its four analogs. After incubation, the samples were analyzed using liquid chromatography-tandem mass spectrometry. Molecular docking simulations were performed using the crystal structure of CYP1A2 to identify the critical interactions between anthraquinones and human CYP1A2. Obtusifolin potently and selectively inhibited CYP1A2-mediated phenacetin O-deethylation (POD) with a Ki value of 0.031 µM in a competitive inhibitory manner in HLMs, whereas it exhibited negligible inhibitory effect against other P450s (IC50 > 28.6 µM). Obtusifolin also inhibited CYP1A1- and CYP1A2-mediated POD and ethoxyresorufin O-deethylation with IC50 values of <0.57 µM when using recombinant enzymes. Our molecular docking models suggested that the high CYP1A2 inhibitory activity of obtusifolin may be attributed to the combination of hydrophobic interactions and hydrogen bonding. This is the first report of selective and potent inhibitory effects of obtusifolin against CYP1A, indicating their potential chemopreventive effects.

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Section: Inhibition Of Cyp1a2 Activity By Five Major Phytochemicals F...mentioning

confidence: 90%

Section: Lc-ms/ms Analysismentioning

confidence: 99%

Potent and Selective Inhibition of CYP1A2 Enzyme by Obtusifolin and Its Chemopreventive Effects

Park

Park²,

Durai³

et al. 2022

Pharmaceutics

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“…Here it is important to comment that a drug interaction effect of RSV (especially in high doses) has already been described in the literature, mainly related to drug-and carcinogen-metabolizing enzymes such as cytochrome. 35 Most studies were performed in vitro and in animal models; in humans, few studies emphasize this issue, 36 but they point out that the main negative effects in relation to RSV occur at high supplementation dosages. In clinical trials, there was observed modified pharmacokinetics of carbamazepine (a CYP3A substrate) 37 and chlorzoxazone (a CYP2E1 substrate) 38 when RSV was used for 10 days at 500 mg. High intakes of RSV have also been reported to inhibit the activity of CYP3A4 in vitro and in vivo, which metabolized drugs as 3-hydroxy3-methylglutarylcoenzyme A reductase inhibitors, calcium-channel antagonists, antiarrhythmic agents, human immunodeficiency virus protease 36 Although it has been reported that resveratrol seems to be a low-affinity substrate of CYP3A4, 39 in a clinical trial, it has observed an increase in the bioavailability of CYP3A4, a weak induction of CYP1A1 and CYP1A2, and a reduction in the activity of CYP2D6 and CYP2C9 after administering 1 g of RSV per day for 4 weeks.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol Treatment of Autism Spectrum Disorder—A Pilot Study

et al. 2022

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Objectives: Considering autism spectrum disorder (ASD) as a neurodevelopmental condition associated with immune system impairments, we aimed to evaluate the potential benefits, efficacy, tolerability, and safety of the anti-inflammatory, antioxidant, and neuroprotective trans-resveratrol (RSV) in behavioral impairments and in a set of 8 microRNAs (miR) related to the immune system in pediatric subjects with ASD. Methods:This is an open-label pilot trial over a 3 months (90 days) study follow-up period designed to assess the effect of 200 mg/d RSV on 5 boys aged 10 to 13 (11.8 ± 1.1) years diagnosed with ASD according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Results:The RSV treatment significantly reduced the Aberrant Behavior Checklist total score ( P = 0.042) and Irritability ( P = 0.041), with no alteration in Stereotypical Behavior ( P = 0.066), Hyperactivity ( P = 0.068), and Lethargy/Social Withdrawal ( P = 0.078) subscales. On the Clinical Global Impression scale, 3 individuals showed marked improvement in behavior; one showed mild improvement, and the other had no changes. The RSV treatment increased the miR-195-5p ( P = 0.043), an important modulator of targets related to inflammatory and immunological pathways. RSVadministration did not present adverse effects and did not alter clinical laboratory results.Conclusions: RSV is a safe molecule for administrating in the pediatric population, able to modulate behavior alterations and molecules associated with the immune system, becoming a promising therapeutic strategy for large-scale studies in ASD, to investigate both behavioral and molecular approaches.

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“…Resveratrol can protect from cardiac insufficiency and cardiac fibrosis, induced by high blood pressure, by inhibiting the PTEN/AKT/Smad2/3 and NF-kB signaling pathway, resulting in heart protection. For example, it inhibits cytochrome P450 (CYP) [ 60 ].…”

Section: Wine Bioactive Compounds: Modulation Of Biochemical Pathways...mentioning

confidence: 99%

Moderate Wine Consumption and Health: A Narrative Review

et al. 2022

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Although it is clearly established that the abuse of alcohol is seriously harmful to health, much epidemiological and clinical evidence seem to underline the protective role of moderate quantities of alcohol and in particular of wine on health. This narrative review aims to re-evaluate the relationship between the type and dose of alcoholic drink and reduced or increased risk of various diseases, in the light of the most current scientific evidence. In particular, in vitro studies on the modulation of biochemical pathways and gene expression of wine bioactive components were evaluated. Twenty-four studies were selected after PubMed, Scopus and Google Scholar searches for the evaluation of moderate alcohol/wine consumption and health effects: eight studies concerned cardiovascular diseases, three concerned type 2 diabetes, four concerned neurodegenerative diseases, five concerned cancer and four were related to longevity. A brief discussion on viticultural and enological practices potentially affecting the content of bioactive components in wine is included. The analysis clearly indicates that wine differs from other alcoholic beverages and its moderate consumption not only does not increase the risk of chronic degenerative diseases but is also associated with health benefits particularly when included in a Mediterranean diet model. Obviously, every effort must be made to promote behavioral education to prevent abuse, especially among young people.

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Comprehensive Investigation of Stereoselective Food Drug Interaction Potential of Resveratrol on Nine P450 and Six UGT Isoforms in Human Liver Microsomes

Cited by 8 publications

References 60 publications

Potent and Selective Inhibition of CYP1A2 Enzyme by Obtusifolin and Its Chemopreventive Effects

Potent and Selective Inhibition of CYP1A2 Enzyme by Obtusifolin and Its Chemopreventive Effects

Resveratrol Treatment of Autism Spectrum Disorder—A Pilot Study

Moderate Wine Consumption and Health: A Narrative Review

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