title: CYP450 mediated inhibition potential of Swertia chirata: An herb from Indian traditional medicine.
abstract: BACKGROUND
  An Ayurvedic herb, Swertia chirata (SC) have been used in treating various ailments such as hyperglycemia, leishmania, liver infections, inflammation, abdominal pain, bacterial infection, malaria etc. in Indian Systems of Medicine (ISM).
  
  
  OBJECTIVE
  Study was designed to investigate the inhibition potential of the standardized SC extract along with its bioactive molecule ursolic acid on hepatic drug metabolizing isozymes (CYP3A4 and CYP2D6) and further some heavy metals were also analysed of the plant material.
  
  
  METHODS
  The hydro-alcoholic extract was standardized with standard ursolic acid by reverse phase-high performance liquid chromatography (RP-HPLC) method and the heavy metals content were analyzed through atomic absorption spectroscopy (AAS). The effect of extract on rat liver microsome (RLM) and individual CYP isozymes (CYP3A4 and CYP2D6) was investigated through CYP450-CO complex assay and fluorescence microplate assay respectively.
  
  
  RESULTS
  The content of ursolic acid was found to be 2.66% (w/w) in the SC extract and heavy metal contents along with trace elements were within the prescribed limits as per WHO guidelines. The inhibitory potential of SC extract on RLM was found to be 23.64±1.80%. CYP3A4 and CYP2D6 inhibitory effect of SC and ursolic acid (IC50: 197.49±2.68, 211.45±3.54 and IC50: 229.25±2.52, 212.66±1.26 µg/mL) was less as compared to that known inhibitors, ketoconazole and quinidine respectively.
  
  
  CONCLUSIONS
  The current study revealed that S. chirata has less inhibition potential with two major drug metabolizing isozymes CYP3A4 and CYP2D6. SC extract and ursolic acid showed significantly (P<0.001) less inhibitory potential on RLM. The Ayurvedic herb (SC) has shown less inhibitory activity in a concentration dependent manner against the tested two CYP450 enzymes. The tested heavy metals and trace elements present SC was within limit. Therefore, the traditional use of S. chirata may be safe in respect of both tested isozymes.
authors.affiliation: School of Natural Product Studies, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India.
authors.forename: Sk Milan
authors.initials: SM
authors.lastname: Ahmmed
authors.affiliation: School of Natural Product Studies, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India. Electronic address: naturalproductm@gmail.com.
authors.forename: Pulok K
authors.initials: PK
authors.lastname: Mukherjee
authors.affiliation: School of Natural Product Studies, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India.
authors.forename: Shiv
authors.initials: S
authors.lastname: Bahadur
authors.affiliation: School of Natural Product Studies, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India.
authors.forename: Ranjit K
authors.initials: RK
authors.lastname: Harwansh
authors.affiliation: School of Natural Product Studies, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Kar
authors.affiliation: CSIR- Indian Institute of Chemical Biology, Kolkata 700032, India.
authors.forename: Arun
authors.initials: A
authors.lastname: Bandyopadhyay
authors.affiliation: Department of Botany and Microbiology, Addiriyah Chair for Environmental Studies, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
authors.forename: Naif Abdullah
authors.initials: NA
authors.lastname: Al-Dhabi
authors.affiliation: Department of Botany and Microbiology, Addiriyah Chair for Environmental Studies, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
authors.forename: V
authors.initials: V
authors.lastname: Duraipandiyan
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D041743:Herb-Drug Interactions / Q000502:physiology; D007194:India; D020128:Inhibitory Concentration 50; D007654:Ketoconazole / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008519:Medicine, Traditional / Q000379:methods; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D029967:Swertia / Q000737:chemistry*; D014315:Triterpenes / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000097245:Ursolic Acid
chemical_list: D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D007654:Ketoconazole; D010936:Plant Extracts; D014315:Triterpenes; D000097245:Ursolic Acid
keywords: Cytochrome P450; Indian traditional medicine; Inhibition potential; Swertia chirata; Ursolic acid