title: Isolation, identification and molecular docking studies of a new isolated compound, from Onopordon acanthium: a novel angiotensin converting enzyme (ACE) inhibitor.
abstract: BACKGROUND
  Onopordon acanthium (also known as Scotch thistle) is a medicinal plant of the Asteraceae family that is widely distributed in Europe and Asia. This plant has been long used in traditional medicine as a hypotensive, cardiotonic and diuretic agent.
  
  
  OBJECTIVE
  The present study is designed to isolate an active compound with ACE inhibition activity from O. acanthium, measure antioxidant activity, predict domain specificity and pharmacokinetic properties of the isolated compound.
  
  
  METHODS
  Methanolic extract of O. acanthium seeds, has been subjected to a repeated column chromatography to give a pure compound with Angiotensin Converting Enzyme (ACE) inhibition activity. The ACE inhibition activity was determined using hippuryl-L-histidyl-L-leucine (HHL) as substrate in an in vitro ACE assay. Structure of the pure compound, isolated from O. acanthium has been established by spectroscopic methods, including Infrared (IR), Nuclear Magnetic Resonance (NMR) and Mass spectrum analysis. In addition, antioxidant activity of the new isolated compound, was measured using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and compared with those of BHT and Trolox as positive controls. Enzyme type inhibition and ACE-C or N domain specificity of the new compound was further evaluated through molecular modeling and docking studies.
  
  
  RESULTS
  Structure of the pure compound, isolated from O. acanthium (83±1% ACE inhibition activity at concentration of 330 μg/ml), has been established. The isolated compound possessed acceptable antioxidant activity (IC50 value of 2.6±0.04 μg/ml) in comparison with BHT (IC50 value of 10.3±0.15 μg/ml) and Trolox (IC50 value of 3.2±0.06 μg/ml). Molecular docking predicted competitive type enzyme inhibition and approximately similar affinity of the isolated compound for ACE-C and N domains.
  
  
  CONCLUSIONS
  The results derived from computational and in vitro experiments, confirm the potential of the isolated compound, from O. acanthium as a new antihypertensive compound and give additional scientific support to an anecdotal use of O. acanthium in traditional medicine to treat cardiovascular disease such as hypertension.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Niusha
authors.initials: N
authors.lastname: Sharifi
authors.forename: Effat
authors.initials: E
authors.lastname: Souri
authors.forename: Seyed Ali
authors.initials: SA
authors.lastname: Ziai
authors.forename: Gholamreza
authors.initials: G
authors.lastname: Amin
authors.forename: Mohsen
authors.initials: M
authors.lastname: Amini
authors.forename: Massoud
authors.initials: M
authors.lastname: Amanlou
mesh_terms: D000179:Acrylates / Q000302:isolation & purification / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D019659:Asteraceae; D049934:Isocoumarins / Q000302:isolation & purification / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D010936:Plant Extracts / Q000494:pharmacology*; D012639:Seeds
chemical_list: C586024:(E)-1-oxo-3,4-dihydro-1H-isochromen-7-yl 3-(3,4-dihydroxyphenyl)acrylate; D000179:Acrylates; D000806:Angiotensin-Converting Enzyme Inhibitors; D049934:Isocoumarins; D010936:Plant Extracts
keywords: Angiotensin Converting Enzyme; Antioxidant activity; Hypertension; Molecular docking; Onopordon acanthium