title: Isolation, characterization, and in silico, in vitro and in vivo antiulcer studies of isoimperatorin crystallized from Ostericum koreanum.
abstract: BACKGROUND
  Ostericum koreanum (Maxim.) Kitagawa (Apiaceae) roots are traditionally used as an analgesic and antiulcer agent. However, the antiulcer potential of isoimperatorin isolated from O. koreanum has not yet been explored.
  
  
  OBJECTIVE
  To evaluate the antiulcer activity of isoimperatorin isolated from the roots of O. koreanum.
  
  
  METHODS
  Isoimperatorin was isolated as cubic crystals by repeated column chromatography of the ethyl acetate fraction and structure was verified with1H NMR,13C NMR and high-resolution mass spectrometry (HRMS-FAB). The crystals obtained were analyzed with the single crystal X-ray method. The MTT assay was used to determine its cytotoxicity against chondrocytes at different concentrations (0.0-737.74 μM, 24 h). The in vivo antiulcer activity of isoimperatorin (40 mg/kg) was determined against ethanol-, indomethacin- and pyloric ligation-induced ulcers in Sprague-Dawley rats. Furthermore, the effect of isoimperatorin (0.0-737.74 μM, 24 h) on the expression of type II collagen in chondrocytes was determined using western blot method. The in vitro urease inhibitory activity of isoimperatorin (0-80 μM) and molecular docking was also performed against urease.
  
  
  CONCLUSIONS
  Isoimperatorin demonstrated significant inhibitory activity (IC5036.43 μM) against urease as compared to the standard drug thiourea (IC5033.57 μM) without cytotoxic effects. It provided 70.9%, 67.65% and 54.25% protection in ulcer models induced by ethanol, indomethacin and pyloric ligation, respectively. Isoimperatorin showed the highest expression level of type II collagen at 368.87 μM. The docking results confirmed strong binding affinity with the target protein.
  
  
  CONCLUSIONS
  Isoimperatorin may be used to develop antiulcer drugs with decreased side effects.
authors.affiliation: a Department of Biological Sciences College of Natural Sciences , Kongju National University , Gongju , Chungnam , Republic of Korea.
authors.forename: Hussain
authors.initials: H
authors.lastname: Raza
authors.affiliation: a Department of Biological Sciences College of Natural Sciences , Kongju National University , Gongju , Chungnam , Republic of Korea.
authors.forename: Qamar
authors.initials: Q
authors.lastname: Abbas
authors.affiliation: a Department of Biological Sciences College of Natural Sciences , Kongju National University , Gongju , Chungnam , Republic of Korea.
authors.forename: Mubashir
authors.initials: M
authors.lastname: Hassan
authors.affiliation: a Department of Biological Sciences College of Natural Sciences , Kongju National University , Gongju , Chungnam , Republic of Korea.
authors.forename: Seong-Hui
authors.initials: SH
authors.lastname: Eo
authors.affiliation: a Department of Biological Sciences College of Natural Sciences , Kongju National University , Gongju , Chungnam , Republic of Korea.
authors.forename: Zaman
authors.initials: Z
authors.lastname: Ashraf
authors.affiliation: b Department of Chemistry , Chungnam National University , Daejeon , Republic of Korea.
authors.forename: Daeyoung
authors.initials: D
authors.lastname: Kim
authors.affiliation: a Department of Biological Sciences College of Natural Sciences , Kongju National University , Gongju , Chungnam , Republic of Korea.
authors.forename: Abdul Rehman
authors.initials: AR
authors.lastname: Phull
authors.affiliation: a Department of Biological Sciences College of Natural Sciences , Kongju National University , Gongju , Chungnam , Republic of Korea.
authors.forename: Song Ja
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: b Department of Chemistry , Chungnam National University , Daejeon , Republic of Korea.
authors.forename: Sung Kwon
authors.initials: SK
authors.lastname: Kang
authors.affiliation: a Department of Biological Sciences College of Natural Sciences , Kongju National University , Gongju , Chungnam , Republic of Korea.
authors.forename: Sung-Yum
authors.initials: SY
authors.lastname: Seo
mesh_terms: D000818:Animals; D000897:Anti-Ulcer Agents / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D019661:Apiaceae / Q000737:chemistry*; D001665:Binding Sites; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D003460:Crystallization; D018360:Crystallography, X-Ray; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology; D000431:Ethanol; D011564:Furocoumarins / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D007213:Indomethacin; D008024:Ligands; D008026:Ligation; D008297:Male; D013058:Mass Spectrometry; D062105:Molecular Docking Simulation; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D018517:Plant Roots; D010946:Plants, Medicinal; D011485:Protein Binding; D066244:Proton Magnetic Resonance Spectroscopy; D011708:Pylorus / Q000601:surgery; D011817:Rabbits; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D014510:Urease / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism
chemical_list: D000897:Anti-Ulcer Agents; D024043:Collagen Type II; D004791:Enzyme Inhibitors; D011564:Furocoumarins; D008024:Ligands; D010936:Plant Extracts; C055542:isoimperatorin; D000431:Ethanol; D014510:Urease; D007213:Indomethacin
keywords: Medicinal plants; molecular docking; type II collagen; urease inhibition