Gastroprotective Effects And Mechanisms Of Ginseng Polysaccharide On Ethanol-induced Injury In Rats

Gastric ulcer is one of the serious gastrointestinal diseases,which poses a significant threat for human beings.It develops as a result of the imbalance between some aggressive and defensive factors.The conventional drugs applied in the clinical studies have an effective impact on gastric ulcer,but followed by a variety of side effects in the long term.Polysaccharides have the gastroprotective effects due to their low toxicity and extensive treatments,however,little is known about the mechanisms.Objective:Our study aims at investigating the gastroprotective effects and mechanisms of Ginseng polysaccharide on ethanol-induced injury in rats.Methods:70 male Wistar rats were divided into 7 groups with 10 animals each: control group,model group,low dose of GPS(100 mg/kg),high dose of GPS(200 mg/kg),low dose of GP(20 mg/kg),high dose of GP(40 mg/kg),OMZ group(40 mg/kg).Control and model group were given distilled water,the rest of groups were administrated with drugs 10 mL/kg each day respectively.All treatments were received by intragastric gavage(i.g.)and recorded the rats weight for two consecutive weeks.The whole animals were deprived of food but allowed free access to water for 24 h before sacrifice.One hour after the last pretreatment,all animals were induced by 0.5 mL/kg 90% ethanol except the rats in the control group.One hour later,all rats were killed decapitation,and the stomachs were removed and dissected.Rats were evaluated the gastric ulcer index(UI)and ulcer inhibition rate.The pathologies of gastric mucosa were objected by Hematoxylinand Eosin(HE)and Periodic acid-Schiff(PAS)staining.The activities of SOD,CAT,MPO and the levels of NO,PGE2,MDA,IL-6,IL-1?,TNF-? in gastric samples were measured by biochemical kits.Based on above,the phosphorylation pattern of NF-?B and STAT3 in stomach were analyzed by Western Blot.Results:(1)UI was significantly increased compared with the control group(P < 0.01).The GPS(100,200 mg/kg),GP(20,40mg/kg)and OMZ groups markedly reduced the changes of UI compared with model group(P < 0.01 or P < 0.05).(2)Pathological examination of gastric tissue stained by HE was completely intact with none of any damage in the control group.Contrary to the control group,stomach sections in model group existed rather substantial gastric erosion such as gastric mucosal epithelium were severely disrupted and massive developments of hyperemia,a mass of inflammatory cells infiltrated into mucosal latent layer.Rats pretreated with GPS at 100 mg/kg decreased gastric damage and infiltrations of inflammatory cells,GPS at 200 mg/kg and OMZ presented a markedly effective protection on the development of inflammatory damage in the gastric mucosa,rats administrated with GP at 20 and 40 mg/kg showed the protection of gastric mucosa and alleviation of mucosal edema.(3)Pathological examination of gastric tissue stained by PAS displayed intact positive PAS staining in control group.Compared with control group,extensive edema,leukocyte infiltration of the submucosal layer were observed,positive staining disappeared,in the model rats.GPS 100 mg/kg group,showed regeneration and restoration of gastric mucosa,GPS 200 mg/kg and OZM groups presented intense regeneration and restoration of gastric mucosa,the effects on regeneration and restoration of gastric mucosa in GP 20 and 40 mg/kg group were better than model group and lower than GPS groups.(4)NO and PGE2 levels were markedly decreased in model group compared with control group(P < 0.01).GPS(100 and 200 mg/kg),GP(20 and 40 mg/kg)and OMZ increased the contents of NO and PGE2 significantly compared with model group(P < 0.01 or P < 0.05).(5)Ethanol-treated rats exhibited substantially increased levels of gastric mucosal MDA,whereas their gastric mucosal SOD and CAT activities were notably decreased compared with control rats(P < 0.01).GPS(100 and 200 mg/kg),GP(20 and 40 mg/kg)and OMZ decreased the content of MDA and activities of gastric mucosal SOD and CAT significantly compared to model group(P < 0.01 or P < 0.05).(6)Model group showed the remarkable increases about the activity of MPO,levels of IL-6,IL-1? and TNF-?,compared with control group(P < 0.01 or P < 0.05).Compared with model group,pretreatments with GPS(100 and 200 mg/kg)showed the substantial reductions about the activity of MPO,levels of IL-6 and IL-1?(P < 0.05),there was a decrease about the level of TNF-? but no statistic meaning(P > 0.05),GP 20 mg/kg and OZM remarkably reduced the activity of MPO and level of IL-6(P < 0.05),and showed a decline for the levels of IL-1? and TNF-? but they were not meaningful statistically(P > 0.05),GP 40 mg/kg significantly decreased the activity of MPO,levels of IL-6,IL-1? and TNF-?(P < 0.05).(7)Model rats displayed a pronounced increase for the phosphorylated NF-?B protein expression and a decrease of I?B? compared with control rats(P < 0.01).GPS and OZM pretreatments remarkably decreased the phosphorylation pattern of NF-?B and increased expression of I?B? compared with model rats(P < 0.01).(8)Model rats notably increased the phosphorylated JAK2 and STAT3 protein expressions(P < 0.01),GPS and OZM pretreatments strikingly decreased the phosphorylation pattern of JAK2 and STAT3 compared with model rats(P < 0.01 or P < 0.05).Conclusions:In this study,GPS and GP exhibited a pronounced gastroprotective effects on ethanol-induced injury in rats.Our results presented GPS and GP significantly increased the contents of NO and PGE2,improved the ability to against aggression,meanwhile,they inhibited the development of oxidative stress and raised the antioxidative bioactivity,the character of anti-inflammation in GPS groups were better than GP groups.The gastroprotective effects of GPS on ethanol-induced injury in rats were highly related to activation of STAT3 and NF-?B signaling pathways...