Evaluation of protective effects of costunolide and dehydrocostuslactone on ethanol induced gastric ulcer in mice based on multi pathway regulation.
The aim of the present study was to evaluate the anti ulcerogenic activity of costunolide (Co) and dehydrocostuslactone (De) on ethanol induced gastric ulcer in mice and to elucidate the potential mechanisms of the action involved. Mice were pretreated orally with Co (5 or 20 mg/kg) De (5 or 20 mg/kg) and omeprazole (OME, 20 mg/kg) for 7 consecutive days, followed by ulcer induction using absolute ethanol (0.2 mL/20 g body weight) Treatment with Co had a remarkable gastroprotection compared to the ethanol ulcerated mice that significantly reduced the ulcerative lesion index (ULI) and histopathological damage. Daily intragastric administration of Co exerted a powerful anti inflammatory activity as evidenced by the suppression of nuclear factor (NF) kB, tumor necrosis factor (TNF) a, nitric oxide (NO) inducible nitric oxide synthase (iNOS) cyclooxygenase (COX) 2, as well as increased interleukin (IL) 10. Also, pretreatment with Co effectively inhibited ethanol induced malondialdehyde (MDA) overproduction, increased the depleted superoxide dismutase (SOD) and promoted gastric mucosa epithelial cell proliferation by up regulating proliferating cell nuclear antigen (PCNA) expression. Similarly, De had a protective effect on ethanol induced ulcer, which was dependent on the inhibition of inflammatory cytokines and MDA generation, but independent of IL 10, SOD and PCNA improvement. Conclusively, the results have clearly demonstrated the anti ulcerogenic potential of Co and De on ethanol induced gastric ulcer; nevertheless, the gastroprotective activity of Co was superior to De due to more multi pathway regulation than De. These findings suggested that Co or De could be a new useful natural gastroprotective tool against gastric ulcer, which provided a scientific basis for the gastroprotection of sesquiterpene lactones.
Chemico biological interactions