Gastroprotective effects of ursolic acid isolated from Ochrosia elliptica on ethanol-induced gastric ulcer in rats

  • Abdelsamed I. Elshamy
  • Abdel-Razik H. Farrag
  • Safaa H. Mohamed
  • Naglaa A. Ali
  • Tarik A. Mohamed
  • Medhat M. Menshawy
  • Asmaa W. Zaglool
  • Thomas Efferth
  • Mohamed-Elamir F. HegazyEmail author
Original Research


The prevention of gastric ulcer pathogenesis or its recurrence is currently one of the main goals of clinical and experimental studies. This study was conducted to investigate the gastroprotective effects of ursolic acid (UA) isolated from the dichloromethane/methanol extract of shoots of Ochrosia elliptica Labill. and investigated for its activity against an ethanol-induced gastric ulcer model in rats. Fifty-six female albino rats were divided into seven groups (eight rats per group): The first group served as control; group 2: absolute ethanol group (5 ml/kg. b.w.); group 3: ranitidine pretreated group (50 mg/kg, i.p.); group 4: UA (100 mg/kg, b.w.); and groups from 5 to 7 were pretreated with UA (25, 50, and 100 mg/kg, b.w.). Then, all animals were sacrificed, and the stomachs were excised for examination. Gastric mucosal injuries were assessed by gross examination, histopathology, immunohistochemistry of caspase-3, and biochemical parameters, including tissue malondialdehyde (MDA) and total antioxidant capacity (TAC) levels. The ethanol group showed severe mucosal injury compared with UA-treated animals, which grossly showed significant reductions of ulcer areas. Histopathologically, they showed marked reductions of mucosal necrosis, edema, and leukocyte infiltrations. Significant increased TAC levels were associated with reduced MDA levels UA-treated rats. In addition, the caspase-3 activity was downregulated. These findings indicated gastroprotective effects of UA at the administered doses comparable with that observed with the control drug ranitidine through suppression of mucosal oxidative stress and antiapoptotic activities. Molecular docking studies showed that UA binds to H+/K+ ATPase more than omeprazole and ranitidine −9.23 vs. −7.09 and 6.29 kcal/mol). In addition, the pKi value of UA was also lower than omeprazole and ranitidine (169.6 nM vs. 6.3 and 26.7 µM). The molecular docking findings suggested the protection role of UA against ethanol-induced gastric ulcer.


Gastric ulcer Ursolic acid Anti-inflammatory activity Apoptosis Oxidative stress Molecular docking 



Financial support for this work was provided by National Research Centre, Giza, Egypt. AIE wishes to gratefully acknowledge Takeda Science Foundation, Japan for the financial support. MEFH gratefully acknowledges the financial support from Alexander von Humboldt Foundation “Georg Foster Research Fellowship for Experienced Researchers”.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Abdelsamed I. Elshamy
    • 1
    • 2
  • Abdel-Razik H. Farrag
    • 3
  • Safaa H. Mohamed
    • 4
  • Naglaa A. Ali
    • 4
  • Tarik A. Mohamed
    • 5
  • Medhat M. Menshawy
    • 6
  • Asmaa W. Zaglool
    • 7
  • Thomas Efferth
    • 8
  • Mohamed-Elamir F. Hegazy
    • 5
    • 8
    Email author
  1. 1.Natural Compounds Chemistry DepartmentNational Research CentreGizaEgypt
  2. 2.Faculty of Pharmaceutical SciencesTokushima Bunri UniversityTokushimaJapan
  3. 3.Departments of PathologyNational Research CentreGizaEgypt
  4. 4.Hormones, National Research CentreCairoEgypt
  5. 5.Chemistry of Medicinal Plants DepartmentNational Research CentreGizaEgypt
  6. 6.Department of Biology, Center of Basic Sciences, College of PharmacyMisr University for Science and Technology6th October CityEgypt
  7. 7.Department of Animal Wealth Development, Faculty of Veterinary MedicineZagazig UniversityZagazigEgypt
  8. 8.Department of Pharmaceutical Biology, Institute of Pharmacy and BiochemistryJohannes Gutenberg UniversityMainzGermany

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