Computer-Aided (In Silico) Modeling of Cytochrome P450-Mediated Food–Drug Interactions (FDI)

Guttman, Yelena; Kerem, Zohar

doi:10.3390/ijms23158498

Cited by 13 publications

(6 citation statements)

References 101 publications

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“…Cytochrome P450 (CYP) enzymes play a vital role in metabolizing various substances in the body, including drugs and xenobiotics [ 39 ]. Inhibition of these enzymes can affect drug clearance and increase the risk of toxicity [ 40 ]. Additionally, the evaluation of toxic behavior suggests that none of the promising compounds are hERG blockers, which eliminates the risk of cardiac toxicity.…”

Section: Discussionmentioning

confidence: 99%

LC/MS-MS Analysis of Phenolic Compounds in Hyoscyamus albus L. Extract: In Vitro Antidiabetic Activity, In Silico Molecular Docking, and In Vivo Investigation against STZ-Induced Diabetic Mice

et al. 2023

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This study aimed to investigate the chemical composition and antidiabetic properties of cultivated Hyoscyamus albus L. The ethanol extract was analyzed using LC-MS/MS, and 18 distinct phenolic compounds were identified. Among these, p-coumaric acid (6656.8 ± 3.4 µg/g), gallic acid (6516 ± 1.7 µg/g), luteolin (6251.9 ± 1.3 µg/g), apigenin (6209.9 ± 1.1 µg/g), and rutin (5213.9 ± 1.3 µg/g) were identified as the most abundant polyphenolic molecules. In the in vitro antidiabetic experiment, the ability of the plant extract to inhibit α-glucosidase and α-amylase activities was examined. The results indicated that the extract from H. albus L. exhibited a higher inhibitory effect on α-amylase compared to α-glucosidase, with an IC50 of 146.63 ± 1.1 µg/mL and 270.43 ± 1.1 µg/mL, respectively. Docking simulations revealed that luteolin, fisetin, and rutin exhibited the most promising inhibitory activity against both enzymes, as indicated by their high contrasting inhibition scores. To further investigate the in vivo antidiabetic effects of H. albus L., an experiment was conducted using STZ-induced diabetic mice. The results demonstrated that the plant extract effectively reduced the levels of cholesterol and triglycerides. These findings suggest that H. albus L. may have therapeutic potential for managing hyperlipidemia, a common complication associated with diabetes. This highlights its potential as a natural remedy for diabetes and related conditions.

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Section: Discussionmentioning

confidence: 99%

LC/MS-MS Analysis of Phenolic Compounds in Hyoscyamus albus L. Extract: In Vitro Antidiabetic Activity, In Silico Molecular Docking, and In Vivo Investigation against STZ-Induced Diabetic Mice

et al. 2023

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“…CYP or Cytochrome 450 is an enzyme that plays a role in the digestive system and Phase 1 metabolic processes. 46 These three test compounds had no inhibition of these various types of CYP enzymes. The last pharmacokinetic parameter to consider is the excretory system.…”

Section: Discussionmentioning

confidence: 96%

In silico Study of Antiviral Activity of Polyphenol Compounds from Ocimum basilicum by Molecular Docking, ADMET, and Drug-Likeness Analysis

Kurnia¹,

Putri²,

Tumilaar³

et al. 2023

AABC

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The SARS-CoV-2 virus is a disease that has mild to severe effects on patients, which can even lead to death. One of the enzymes that act as DNA replication is the main protease, which becomes the main target in the inhibition of the SARS-CoV-2 virus. In finding effective drugs against this virus, Ocimum basilicum is a potential herbal plant because it has been tested to have high phytochemical content and bioactivity. Apigenin-7-glucuronide, dihydrokaempferol-3-glucoside, and aesculetin are polyphenolic compounds found in Ocimum basilicum. Purpose: The purpose of this study was to analyze the mechanism of inhibition of the three polyphenolic compounds in Ocimum basilicum against the main protease and to predict pharmacokinetic activity and the drug-likeness of a compound using the Lipinski Rule of Five. Patients and Methods: The method used is to predict the molecular docking inhibition mechanism using Autodock 4.0 tools and use pkcsm and protox online web server to analyze ADMET and Drug-likeness. Results:The binding affinity for apigenin-7-glucuronide was −8.77 Kcal/mol, dihydrokaempferol-3-glucoside was −8.96 Kcal/mol, and aesculetin was −5.79 Kcal/mol. Then, the inhibition constant values were 375.81 nM, 270.09 nM, and 57.11 µM, respectively. Apigenin-7-glucuronide and dihydrokaempferol-3-glucoside bind to the main protease enzymes on the active sites of CYS145 and HIS41, while aesculetin only binds to the active sites of CYS145. On ADMET analysis, these three compounds met the predicted pharmacokinetic parameters, although there are some specific parameters that must be considered especially for aesculetin compounds. Meanwhile, on drug-likeness analysis, apigenin-7-glucuronide and dihydrokaempferol-3-glucoside compounds have one violation and aesculetin have no violation. Conclusion: Based on the data obtained, Apigenin-7-glucuronide and dihydrokaempferol-3-glucoside are compounds that have more potential to have an antiviral effect on the main protease enzyme than aesculetin. Based on pharmacokinetic parameters and druglikeness, three compounds can be used as lead compounds for further research.

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“…Increasing our understanding on PK and PD interaction mechanisms and utilization of novel experimental procedures will allow the gap on the available evidence regarding food effects on drugs to decrease. The incorporation of biomedical methods will allow the better prediction of potential interactions even through in silico methods during drug development or through big-data analysis [192][193][194]. From the citizen's perspective, the harnessing of digital evolution in relation to health promotion also cannot go unnoticed.…”

Section: Discussionmentioning

confidence: 99%

Drug-Food Interactions with a Focus on Mediterranean Diet

Spanakis

Patelarou

2022

Applied Sciences

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There is a growing interest among people in western countries for adoption of healthier lifestyle habits and diet behaviors with one of the most known ones to be Mediterranean diet (Med-D). Med-D is linked with daily consumption of food products such as vegetables, fruits, whole grains, seafood, beans, nuts, olive oil, low-fat food derivatives and limited consumption of meat or full fat food products. Med-D is well-known to promote well-being and lower the risk of chronic conditions such as cardiovascular diseases, diabetes, and metabolic syndrome. On the other hand bioactive constituents in foods may interfere with drugs’ pharmacological mechanisms, modulating the clinical outcome leading to drug-food interactions (DFIs). This review discusses current evidence for food products that are included within the Med-Dand available scientific data suggest a potential contribution in DFIs with impact on therapeutic outcome. Most cases refer to potential modulation of drugs’ absorption and metabolism such as foods’ impact on drugs’ carrier-mediated transport and enzymatic metabolism as well as potential synergistic or antagonistic effects that enhance or reduce the pharmacological effect for some drugs. Adherence to Med-D can improve disease management and overall well-being, but specific foods should be consumed with caution so as to not hinder therapy outcome. Proper patient education and consultation from healthcare providers is important to avoid any conflicts and side effects due to clinically significant DFIs.

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Computer-Aided (In Silico) Modeling of Cytochrome P450-Mediated Food–Drug Interactions (FDI)

Cited by 13 publications

References 101 publications

LC/MS-MS Analysis of Phenolic Compounds in Hyoscyamus albus L. Extract: In Vitro Antidiabetic Activity, In Silico Molecular Docking, and In Vivo Investigation against STZ-Induced Diabetic Mice

LC/MS-MS Analysis of Phenolic Compounds in Hyoscyamus albus L. Extract: In Vitro Antidiabetic Activity, In Silico Molecular Docking, and In Vivo Investigation against STZ-Induced Diabetic Mice

In silico Study of Antiviral Activity of Polyphenol Compounds from Ocimum basilicum by Molecular Docking, ADMET, and Drug-Likeness Analysis

Drug-Food Interactions with a Focus on Mediterranean Diet

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