In vitro and in vivo cytochrome P450 3A enzyme inhibition by Aframomum melegueta and Denniettia tripetala extracts

Nduka, Sunday Odunke; Okonta, Mathew Jegbefume; Ajaghaku, Daniel Lotanna; Ukwe, Chinwe Victoria

doi:10.1016/j.apjtm.2017.06.006

Cited by 5 publications

(3 citation statements)

References 18 publications

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“…The drug interactions are caused by either CYP450 inhibition or induction. Enzyme induction or inhibition by food, drugs, and medicinal herbs, for instance, can be responsible for changes in the metabolic capacity of these enzymes [ 4 ], although inhibition is considered more important in terms of adverse clinical outcomes.…”

Section: Introductionmentioning

confidence: 99%

Development and Validation of a Novel HPLC Method to Analyse Metabolic Reaction Products Catalysed by the CYP3A2 Isoform: In Vitro Inhibition of CYP3A2 Enzyme Activity by Aspirin (Drugs Often Used Together in COVID-19 Treatment)

2022

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Aspirin (also known as acetylsalicylic acid) is a drug intended to treat fever, pain, or inflammation. Treatment of moderate to severe cases of COVID-19 using aspirin along with dexamethasone has gained major attention globally in recent times. Thus, the purpose of this study was to use High-Performance Liquid Chromatography (HPLC) to evaluate the in vitro inhibition of CYP3A2 enzyme activity using aspirin in rat liver microsomes (RLMs). In this study, an efficient and sensitive HPLC method was developed using a reversed phase C18 column (X Bridge 4.6 mm × 150 mm, 3.5 µm) at 243 nm using acetonitrile and water (70:30 v/v). The linearity (r2 > 0.999), precision (<15%), accuracy and recovery (80–120%), limit of detection (5.60 µM and 0.06 µM), limit of quantification (16.98 µM and 0.19 µM), and stability of the newly developed method were validated for dexamethasone and 6β-hydroxydexamethasone, respectively, following International Conference on Harmonization (ICH) guidelines. This method was applied in vitro to measure CYP3A2 activity. The results showed that aspirin competitively inhibits 6β-hydroxylation (CYP3A2 activity) with an inhibition constant (Ki) = 95.46 µM and the concentration of the inhibitor causing 50% inhibition of original enzyme activity (IC50) = 190.92 µM. This indicated that there is a minimal risk of toxicity when dexamethasone and aspirin are co-administrated and a very low risk of toxicity and drug interaction with drugs that are a substrate for CYP3A2 in healthcare settings.

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Section: Introductionmentioning

confidence: 99%

Development and Validation of a Novel HPLC Method to Analyse Metabolic Reaction Products Catalysed by the CYP3A2 Isoform: In Vitro Inhibition of CYP3A2 Enzyme Activity by Aspirin (Drugs Often Used Together in COVID-19 Treatment)

2022

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“…In 2017, D. tripetala powder was shown to be tolerated by rats when incorporated into their diet as a form of botanical pesticide ( Nwosu et al, 2017 ). The aqueous and petroleum ether extracts were also found to elicit inhibitory effects on the activity of CYP3A enzymes in vitro (in rat liver and intestinal microsomes) and in vivo in rats ( Nduka et al, 2017 ). In 2018, ethanolic extracts of D. tripetala fruits were shown to enhance the testosterone levels as well as the number and motility of sperm in rats ( Obiandu and Green, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Dennettia tripetala Combats Oxidative Stress, Protein and Lipid Dyshomeostasis, Inflammation, Hepatic Injury, and Glomerular Blockage in Rats

Omage

Orhue

Omage

2021

Prev. Nutr. Food Sci.

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Dennettia tripetala, better known as 'pepperfruit', is a medicinal plant consumed in West Africa. D. tripetala possesses strong antioxidant properties and contains uvariopsine, an alkaloid which improves bile secretion and liver function. In the present study, the ethanolic extract of D. tripetala fruits was tested for its ability to alleviate pathophysiological conditions bordering on oxidative stress, including protein and lipid dyshomeostasis, inflammation, and hepatic and glomerular injury. Male albino Wistar rats were administered carbon tetrachloride twice a week for two weeks, and the ethanolic extract of D. tripetala fruits was administered from days 8∼14. The serum, liver, and kidneys of the rats were then subjected to biochemical assays and imaging. The extract restored the activities of liver marker enzymes in serum and the concentrations of lipids and proteins in both circulation and the liver to normal. The extract also restored the activities of antioxidant enzymes in liver and kidneys, and the concentrations of urea and creatinine in the blood. The extract also repaired the altered structures of the liver and kidney. Overall, D. tripetala elicited strong medicinal effects in rats. This study showed that the fruits of D. tripetala contain substances that could be extracted or synthesized for use in drugs for the treatment of liver and kidney disease.

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“…The CYP3A enzyme converts ERY into N-desmethylerythromycin and formaldehyde; therefore, the activity of CYP3A is proportional to the amount of formaldehyde formed. Nduka et al [ 14 , 15 ] used this principle to study the effects of Aframomum melegueta , Denniettia , and Millettia aboensis extracts on CYP3A activity in intestinal and liver microsomes. The cytochrome P450 enzymes in liver microsomes of poultry (turkey, duck, quail, and chicken) that are orthologous to cytochrome P450 enzymes in human and mouse liver microsomes are CYP1A1/2, CYP2A6, and CYP3A4 [ 16 , 17 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of Erythromycin and Clarithromycin Metabolites Formed in Chicken Liver Microsomes Using Liquid Chromatography–High-Resolution Mass Spectrometry

Wang

Nam

Kim

et al. 2021

Foods

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Nontargeted analysis can be used for the rapid screening and confirmatory analysis of veterinary drugs and their metabolites, which are important for the comprehensive safety evaluation of animal-derived foods. Here, a novel nontargeted screening approach based on liquid chromatography coupled with electrospray ionization–high-resolution mass spectrometry (LC/ESI–HR-MS) was developed to determine erythromycin, clarithromycin, and their metabolites in chicken liver microsomes. Erythromycin and clarithromycin were incubated in vitro in the presence of NADPH for 60 min to generate metabolites in chicken liver microsomes. After the incubation, the supernatant was extracted using ultrasonic shaking, orbital shaking, and centrifugation before analysis using LC/ESI-HR-MS in positive ion mode on an Agilent Eclipse Plus C18 column (100 mm × 2.1 mm; i.d. 3.5 µm) with 0.1 percent formic acid-water and acetonitrile as the mobile phases for gradient elution at 0.4 mL/min. The results show that erythromycin can produce N-desmethyl-erythromycin A in chicken liver microsomes, but clarithromycin cannot produce N-desmethyl-clarithromycin in chicken liver microsomes. The N-desmethyl-erythromycin A and N-desmethyl-clarithromycin were tentatively identified in chicken liver microsomes using the established quick analytic method, which will provide a theoretical foundation for future research on pharmacokinetics and drug elimination in poultry.

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In vitro and in vivo cytochrome P450 3A enzyme inhibition by Aframomum melegueta and Denniettia tripetala extracts

Abstract: Herbal preparations containing these plants' extracts should be used with caution especially in patients on CYP450 3A substrate medications.

Cited by 5 publications

References 18 publications

Development and Validation of a Novel HPLC Method to Analyse Metabolic Reaction Products Catalysed by the CYP3A2 Isoform: In Vitro Inhibition of CYP3A2 Enzyme Activity by Aspirin (Drugs Often Used Together in COVID-19 Treatment)

Development and Validation of a Novel HPLC Method to Analyse Metabolic Reaction Products Catalysed by the CYP3A2 Isoform: In Vitro Inhibition of CYP3A2 Enzyme Activity by Aspirin (Drugs Often Used Together in COVID-19 Treatment)

Dennettia tripetala Combats Oxidative Stress, Protein and Lipid Dyshomeostasis, Inflammation, Hepatic Injury, and Glomerular Blockage in Rats

Identification of Erythromycin and Clarithromycin Metabolites Formed in Chicken Liver Microsomes Using Liquid Chromatography–High-Resolution Mass Spectrometry

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