The Protective Effects Of Wei-chang-an-wan And Radix Aucklandiae On Gastric Mucosal Lesion

Wei-chang-an-wan(WCA),a traditional Chinese medicine prescription,has been used to treat irritable bowel syndrome and functional diarrhea.The study was aimed to evaluate the anti-ulcerogenic activity of WCA on gastric ulcer in mice model.To further elucidate the potential mechanisms of the action involved,we investigated the protective effects of Radix Aucklandiae(RA),the main herb in WCA,and its major active components,costunolide(Co)and dehydrocostuslactone(De),on ethanol-induced gastric ulcer.Mice were pretreated orally with WCA(0.1,0.2,0.4 g/kg)followed by ulcer induction using different doses of ethanol(50% and 90%),which induced chronic and acute gastric ulcer,respectively.The results showed that WCA could both inhibit the formation of ethanol induced-chronic and acute ulceration.It significantly decreased the high ulcerative lesion index induced by ethanol.The gastroprotection of WCA were supported by histopathological analysis,where severe gastric submucosal edema,hemorrhagic damage,epithelial cell loss and neutrophil infiltration in ulcer-mice were alleviated.Administration of RA(0.2,0.4,0.8 g/kg)decreased the high ulcer index induced by 90% ethanol in a dose-dependent manner,which was the evidence of gastro-protection of WCA.RA pretreated animals showed considerable increasing in antioxidants that significantly improved the activity of superoxide dismutase(SOD)and inhibited the level of malondialdehyde(MDA)in the plasma.Inflammatory cytokines such as nuclear factor kappa B(NF-?B),cyclooxygenase-2(COX-2),and nitric oxide(NO)were increased and the level of interleukin-10(IL-10),an anti-inflammatory cytokine,was decreased in ethanol-induced ulcerated animals,which were amended by RA pretreatment.Moreover,pretreatment with RA was associated with a further enhancement of proliferating cell nuclear antigen(PCNA)expression in the gastric mucosa.These outcomes suggested that the gastroprotective effects of RA might be mediated by adjustment of antioxidant and inflammatory mediators,and increasing cell proliferation.Co and De possessed properties of protection on ethanol-induced gastric ulcer;nevertheless,the gastroprotective activity of Co was superior to De due to more multi-pathway regulation than De.Pretreatment with Co resulted in a remarkable gastroprotection compared to ethanol-ulcerated mice as manifested by significant reductions in ulcerative lesion index and histopathological damage.The potent gastroprotective effect of Co could be partly mediated by inhibiting ethanol-induced inflammation,oxidative stress and decreased cell proliferation.Moreover,the results demonstrated that pretreatment of Co promoted gastric mucosa epithelial cell proliferation by up-regulating PCNA expression.Similarly,De also 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.In addition,the protective effects of WCA on non-steroidal anti-inflammatory drugs(NSAIDs)induced gastric ulcer were preliminarily investigated in this study.The results showed that WCA(0.1,02,0.4 g/kg)could significantly reduce high gastric ulcer index,and effectively retard gastric mucosal damage caused by indomethacin,characterized by improving the mucosal edema,hemorrhage and erosion.Conclusively,these findings suggested that WCA could be a new useful gastroprotective tool against gastric ulcer,which provided a scientific basis for the clinical application and further development of WCA.