Screening of Human CYP1A2 and CYP3A4 Inhibitors from Seaweed In Silico and In Vitro

Yim, Sung-Kun; Kim, Kian; Chun, Sang-Ho; Oh, TaeHawn; Jung, WooHuk; Jung, Kyungsook; Yun, Chul‐Ho

doi:10.3390/md18120603

Cited by 25 publications

(19 citation statements)

References 36 publications

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“…Our results are in agreement with an experimental study mentioning that resveratrol modified the metabolism of aripiprazole by CYP2D6 and CYP3A4 [64]. The predicted inhibitory activity of quercetin on CYP1A2 is supported by a previous study [65] showing that quercetin is able to change the metabolism of melatonin by CYP1A2. Quercetin was also reported to be a strong inhibitor of CYP2D6 and a moderate inhibitor of CYP3A4 [66].…”

Section: Computational Pharmacokinetics and Pharmacogenomics Profiles Of Natural Compoundssupporting

confidence: 92%

3D-ALMOND-QSAR Models to Predict the Antidepressant Effect of Some Natural Compounds

et al. 2021

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The current treatment of depression involves antidepressant synthetic drugs that have a variety of side effects. In searching for alternatives, natural compounds could represent a solution, as many studies reported that such compounds modulate the nervous system and exhibit antidepressant effects. We used bioinformatics methods to predict the antidepressant effect of ten natural compounds with neuroleptic activity, reported in the literature. For all compounds we computed their drug-likeness, absorption, distribution, metabolism, excretion (ADME), and toxicity profiles. Their antidepressant and neuroleptic activities were predicted by 3D-ALMOND-QSAR models built by considering three important targets, namely serotonin transporter (SERT), 5-hydroxytryptamine receptor 1A (5-HT1A), and dopamine D2 receptor. For our QSAR models we have used the following molecular descriptors: hydrophobicity, electrostatic, and hydrogen bond donor/acceptor. Our results showed that all compounds present drug-likeness features as well as promising ADME features and no toxicity. Most compounds appear to modulate SERT, and fewer appear as ligands for 5-HT1A and D2 receptors. From our prediction, linalyl acetate appears as the only ligand for all three targets, neryl acetate appears as a ligand for SERT and D2 receptors, while 1,8-cineole appears as a ligand for 5-HT1A and D2 receptors.

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Section: Computational Pharmacokinetics and Pharmacogenomics Profiles Of Natural Compoundssupporting

confidence: 92%

3D-ALMOND-QSAR Models to Predict the Antidepressant Effect of Some Natural Compounds

et al. 2021

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“…The results showed that cineole and its derivatives had no predicted inhibitory effects as the predicted value was 0 ( Table 2 ). Importantly, ketoconazole (positive control) was predicted accurately with a value of one, indicating that it is a potent CYP3A4 inhibitor [ 21 ].…”

Section: Resultsmentioning

confidence: 99%

In Vitro Hepatic Assessment of Cineole and Its Derivatives in Common Brushtail Possums (Trichosurus vulpecula) and Rodents

Chand

Nimick

Cridge

et al. 2021

Biology

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Folivore marsupials, such as brushtail possum (Trichosurus Vulpecula) and koala (Phascolarctos cinereus), can metabolise higher levels of dietary terpenes, such as cineole, that are toxic to eutherian mammals. While the highly efficient drug metabolising enzymes, cytochrome P450 3A (CYP3A) and phase II conjugating enzymes (UDP-glucuronosyltransferase, UGT), are involved in the metabolism of high levels of dietary terpenes, evidence for inhibitory actions on these enzymes by these terpenes is scant. Thus, this study investigated the effect of cineole and its derivatives on catalytic activities of hepatic CYP3A and UGT in mice, rats, and possums. Results showed that cineole (up to 50 µM) and its derivatives (up to 25 µM) did not significantly inhibit CYP3A and UGT activities in mice, rats, and possums (both in silico and in vitro). Interestingly, basal hepatic CYP3A catalytic activity in the possums was ~20% lower than that in rats and mice. In contrast, possums had ~2-fold higher UGT catalytic activity when compared to mice and rats. Thus, these basal enzymatic differences may be further exploited in future pest management strategies.

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“…Commercially, FX and SX are sold as health supplements because these compounds are believed to possess a variety of health benefits [ 20 , 21 , 22 ]. However, in previous studies, FX inhibited the activity of CYP1A2 and CYP3A4 with an IC50 of 30.3 μM and 24.4 μM, respectively [ 33 , 34 , 35 ]. These CYPs are responsible for the metabolism of more than 60% of commonly prescribed drugs [ 36 ].…”

Section: Discussionmentioning

confidence: 97%

“…Ultra-pure argon (99.99%), nitrogen (99.99%), and carbon dioxide were supplied from Daechang Gas (Songha-dong, Gwangju, South Korea). Fucoxanthin (FX) and siphonaxanthin (SX) were extracted and purified from sporophyll of Undaria pinnatifida and Codium fragile , respectively, for a previous study [ 35 ].…”

Section: Methodsmentioning

confidence: 99%

Antiviral Activity of Two Marine Carotenoids against SARS-CoV-2 Virus Entry In Silico and In Vitro

Yim

Kim

Warren

et al. 2021

IJMS

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The marine carotenoids fucoxanthin and siphonaxanthin are powerful antioxidants that are attracting focused attention to identify a variety of health benefits and industry applications. In this study, the binding energy of these carotenoids with the SARS-CoV-2 Spike-glycoprotein was predicted by molecular docking simulation, and their inhibitory activity was confirmed with SARS-CoV-2 pseudovirus on HEK293 cells overexpressing angiotensin-converting enzyme 2 (ACE2). Siphonaxanthin from Codium fragile showed significant antiviral activity with an IC50 of 87.4 μM against SARS-CoV-2 pseudovirus entry, while fucoxanthin from Undaria pinnatifida sporophyll did not. The acute toxicities were predicted to be relatively low, and pharmacokinetic predictions indicate GI absorption. Although further studies are needed to elucidate the inhibition of viral infection by siphonaxanthin, these results provide useful information in the application of these marine carotenoids for the treatment and prevention of COVID-19.

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Screening of Human CYP1A2 and CYP3A4 Inhibitors from Seaweed In Silico and In Vitro

Cited by 25 publications

References 36 publications

3D-ALMOND-QSAR Models to Predict the Antidepressant Effect of Some Natural Compounds

3D-ALMOND-QSAR Models to Predict the Antidepressant Effect of Some Natural Compounds

In Vitro Hepatic Assessment of Cineole and Its Derivatives in Common Brushtail Possums (Trichosurus vulpecula) and Rodents

Antiviral Activity of Two Marine Carotenoids against SARS-CoV-2 Virus Entry In Silico and In Vitro

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