title: Metabolism-mediated interaction potential of standardized extract ofTinospora cordifoliathrough rat and human liver microsomes.
abstract: OBJECTIVE
  Tinospora cordifoliais used for treatment of several diseases in Indian system of medicine. In the present study, the inhibition potential ofT. cordifoliaextracts and its constituent tinosporaside to cause herb-drug interactions through rat and human liver cytochrome enzymes was evaluated.
  
  
  METHODS
  Bioactive compound was quantified through reverse phase high-performance liquid chromatography, to standardize the plant extracts and interaction potential of standardized extract. Interaction potential of the test sample was evaluated through cytochrome P450-carbon monoxide complex (CYP450-CO) assay with pooled rat liver microsome. Influence on individual recombinant human liver microsomes such as CYP3A4, CYP2D6, CYP2C9, and CYP1A2 isozymes was analyzed through fluorescence microplate assay, and respective IC50values were determined.
  
  
  RESULTS
  The content of tinosporaside was found to be 1.64% (w/w) inT. cordifoliaextract. Concentration-dependent inhibition was observed throughT. cordifoliaextract. Observed IC50(μg/ml) value was 136.45 (CYP3A4), 144.37 (CYP2D6), 127.55 (CYP2C9), and 141.82 (CYP1A2). Tinosporaside and extract showed higher IC50(μg/ml) value than the known inhibitors.T. cordifoliaextract showed significantly less interaction potential and indicates that the selected plant has not significant herb-drug interactions relating to the inhibition of major CYP450 isozymes.
  
  
  CONCLUSIONS
  Plant extract showed significantly higher IC50value than respective positive inhibitors against CYP3A4, 2D6, 2C9, and 1A2 isozymes. Consumption ofT. cordifoliamay not cause any adverse effects when consumed along with other xenobiotics.
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: 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: S K
authors.initials: SK
authors.lastname: Milan Ahmmed
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: Ranjit K
authors.initials: RK
authors.lastname: Harwansh
authors.affiliation: Department of Pharmaceutical Technology, School of Natural Product Studies, Jadavpur University, Kolkata, West Bengal, India.
authors.forename: Subrata
authors.initials: S
authors.lastname: Pandit
mesh_terms: D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D041743:Herb-Drug Interactions; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D031610:Tinospora
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D010936:Plant Extracts; D002248:Carbon Monoxide; D003577:Cytochrome P-450 Enzyme System
keywords: Cytochrome P450; Tinospora cordifolia; human liver microsome; reverse phase high-performance liquid chromatography; tinosporaside