title: Interaction potential of Trigonella foenum graceum through cytochrome P450 mediated inhibition.
abstract: OBJECTIVE
  The seeds of Trigonella foenum-graecum (TFG) (family: Leguminosae) are widely consumed both as a spice in food and Traditional Medicine in India. The present study was undertaken to evaluate the inhibitory effect of standardized extract of TFG and its major constituent trigonelline (TG) on rat liver microsome (RLM) and cytochrome P450 (CYP450) drug metabolizing isozymes (CYP3A4 and CYP2D6), which may indicate the possibility of a probable unwanted interaction.
  
  
  METHODS
  Reverse phase-high performance liquid chromatography method was developed to standardize the hydroalcoholic seed extract with standard TG. The inhibitory potential of the extract and TG was evaluated on RLM and CYP isozymes using CYP450-carbon monoxide (CYP450-CO) complex assay and fluorescence assay, respectively.
  
  
  RESULTS
  The content of TG in TFG was found to be 3.38% (w/w). The CYP-CO complex assay showed 23.32% inhibition on RLM. Fluorescence study revealed that the extract and the biomarker had some inhibition on CYP450 isozymes e.g. CYP3A4 and CYP2D6 (IC50 values of the extract: 102.65 ± 2.63-142.23 ± 2.61 µg/ml and TG: 168.73 ± 4.03-180.90 ± 2.49 µg/ml) which was very less compared to positive controls ketoconazole and quinidine. Inhibition potential of TFG was little higher than TG but very less compared to positive controls.
  
  
  CONCLUSIONS
  From the present study, we may conclude that the TFG or TG has very less potential to inhibit the CYP isozymes (CYP3A4, CYP2D6), so administration of this plant extract or its biomarker TG may be safe.
authors.affiliation: Department of Pharmaceutical Technology, School of Natural Product Studies, Jadavpur University, Kolkata, West Bengal, India.
authors.forename: Sk Milan
authors.initials: SM
authors.lastname: Ahmmed
authors.affiliation: Department of Pharmaceutical Technology, School of Natural Product Studies, Jadavpur University, Kolkata, West Bengal, India.
authors.forename: Pulok K
authors.initials: PK
authors.lastname: Mukherjee
authors.affiliation: Department of Pharmaceutical Technology, School of Natural Product Studies, Jadavpur University, Kolkata, West Bengal, India.
authors.forename: Shiv
authors.initials: S
authors.lastname: Bahadur
authors.affiliation: Department of Pharmaceutical Technology, School of Natural Product Studies, Jadavpur University, Kolkata, West Bengal, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Kar
authors.affiliation: Department of Pharmaceutical Technology, School of Natural Product Studies, Jadavpur University, Kolkata, West Bengal, India.
authors.forename: Kakali
authors.initials: K
authors.lastname: Mukherjee
authors.affiliation: Department of Pharmaceutical Technology, School of Natural Product Studies, Jadavpur University, Kolkata, West Bengal, India.
authors.forename: Sanmoy
authors.initials: S
authors.lastname: Karmakar
authors.affiliation: Indian Institute of Chemical Biology, Jadavpur, Kolkata, India.
authors.forename: Arun
authors.initials: A
authors.lastname: Bandyopadhyay
mesh_terms: D000470:Alkaloids / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D019389:Cytochrome P-450 CYP2D6 / Q000187:drug effects*; D051544:Cytochrome P-450 CYP3A / Q000187:drug effects*; D004347:Drug Interactions; D007194:India; D020128:Inhibitory Concentration 50; D007654:Ketoconazole / Q000494:pharmacology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D011802:Quinidine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012639:Seeds; D029910:Trigonella / Q000737:chemistry*
chemical_list: D000470:Alkaloids; D010936:Plant Extracts; C009560:trigonelline; C465260:Cyp3a2 protein, rat; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; D011802:Quinidine; D007654:Ketoconazole
keywords: Cytochrome enzyme; Trigonella foenum graceum; interaction potential; reverse phase-high performance liquid chromatography; trigonelline