FI Al-Jenoobi, AA Al-Thukair, FA Abbas, MJ Ansari, KM Alkharfy, AM Al-Mohizea, SA Al-Suwayeha, S Jamil. Effect of black seed on Dextromethorphan O-and N- Demethylation in human liver microsomes and healthy human subjects. Drug Metabolism Letters, 2010; 4(1):51-55. (Scopus H index 18).
Abstract: Objective: To investigate the effects of black seed on the metabolic activities of CYP3A4 and CYP2D6 in human
liver microsomes and in human subjects using dextromethorphan as a probe drug. Methods: CYP2D6-mediated Odemethylation
and CYP3A4-mediated N-demethylation of dextromethorphan (DEX) to dextrorphan (DOR) and 3-
methoxymorphinan (3-MM), respectively, were utilized to assess the metabolic activities of the two enzymatic pathways.
In the in vitro experiments, DEX was incubated with microsomes and NADPH in absence or presence of black seed extract
(10–100 μg/ml) and the formation of the metabolites were measured by HPLC. In the clinical study, four healthy
volunteers received a single oral dose of DEX 30 mg alone in phase I, and along with last dose of black seed (2.5 g twice
daily for seven days) in phase II. Activities of the two enzymes were evaluated based on the urinary metabolic ratios
(MRs), which were calculated from eight-hour urine collections. DEX and its metabolites were assayed in urine samples
by HPLC following a liquid-liquid extraction. Results: Black seed extracts significantly inhibited the formation of both
metabolites in microsomes. The maximum inhibition was observed at the highest extract concentration (i.e., 100 μg/ml),
which was about 80% and 60% for DOR and 3-MM, respectively. In the clinical study, the urinary MRs of DEX/DOR
and DEX/3-MM increased by factors of 127 and 1.6-fold, respectively, after consumption of black seed. Conclusion:
Black seed significantly inhibited CYP2D6 and CYP3A4 mediated metabolism of DEX in human liver microsomes and
healthy human volunteers indicating that it has the potential to interact with CYP2D6 and CYP3A4 substrates.
Effect of black seed on Dextromethorphan O-and N- Demethylation in human liver microsomes and health
محتويات مواقع أعضاء هيئة التدريس بما فيها من نصوص وملفات وصور وأبحاث وأية مواد أخرى هي مسئولية عضو هيئة التدريس بالكامل بصفته صاحب الموقع وبما له من صلاحية مطلقة في الإضافة والحذف، وتخلي الجامعة مسئوليتها عن محتويات تلك المواقع.
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