The Pharmacodynamic Studies Of Anti-peptic Ulcer Of The Effective Parts Of Pomegranate Peel Polyphenols

Objection:1.To produce the effective parts of pomegranate peel polyphenols on pilot-scale.2.To study single dose toxicity of the effective parts of pomegranate peel polyphenols,to evaluate their safety,and to provide a theoretical basis for measurement of pharmacodynamic experiment design.3.To study its function and mechanism of anti-ulcer effect of the effective parts of pomegranate peel polyphenols.Methods:The median lethal dose of the effective parts of pomegranate peel polyphenols was calculated by Bliss method,toxicity and death in each group of mice were observed and recorded,to observe morphological changes in various organs by HE.Using ethanol induced gastric ulcer model,to study inhibition and protective of gastric ulcer rats in different concentrations of the effective parts of pomegranate peel polyphenols,the gastric mucosa levels of NO was calculated by nitrate reductase assay,the gastric mucosa levels of MDA was calculated by TBA,the gastric mucosa levels of SOD was calculated by Hydroxylamine,the gastric mucosa levels of PGE2 was calculated by ELISA.Using pylorus ligation induced gasttic ulcer,to study inhibition of gastric ulcer rats in different concentrations of the effective parts of pomegranate peel polyphenols.To calculate the sera and gastric mucosa levels of EGF、TGF-α by ELISA,the level of ulcer tissue protein of EGF,TGF-α,EGFR,IL-8 and NFкB-p65 was calculated by streptavidin-perosidase.Results:The LD50 and 95%confidence limit of the effective parts of pomegranate peel polyphenols were8520.9mg·kg-1 and 7291.2-9914.4mg·kg-1,respectively;the effective parts of pomegranate peel polyphenols was significantly reduced the gastric ulcer index in rats,the effective parts of pomegranate peel polyphenols of high dose group ulcer inhibition rate was98%,significant enhanced mucosal defense and antioxidant capacity,promoted ulcer healing and inhibited the occurrence and development of ulcers.ELISA results showed the effective parts of pomegranate peel polyphenols in the high dose group was promoted the rat epithelial cells synthesize and secrete PGE2(P<0.05),improved mucosal regeneration function.In addition, the effective parts of pomegranate peel polyphenols can reduce the gastric ulcer induced by pyloric ligation method.The effective parts ofpomegranate peel polyphenols of high dose group ulcer inhibition rate was 77%.ELISA results showed the effective parts of pomegranate peel polyphenols of low,middle and high dose groups were significantly increased serum and gastric tissue of EGF,TGF-a(P<0.01),promoted the synthesis and release EGF and epithelial cell proliferation,enhanced gastric mucosal defense,repaired and regeneration.Immunohistochemical results showed the effective parts of pomegranate peel polyphenols of the high dose group was enhanced the expression of mucosa gastric ulcer of EGF and EGFR(P<0.01),the effective parts of pomegranate peel polyphenols of high dose group was significantly enhanced the protein expression of TGF-a(P<0.01);at the same time,significantly inhibited the expression of NF-кB and IL-8.Conclusion:The effective parts of pomegranate peel polyphenols was inhibited peptic ulcer formation in rats.The effective parts of pomegranate peel polyphenols was increased the level of NO,SOD,PGE2,EGF,TGF-a,enhanced the protein expression of EGF,EGFR,TGF-a,reduced the level of MDA and inhibited the expression of inflammatory cytokines IL-8 and NF-кB,it was proved the effective parts of pomegranate peel polyphenols can enhance gastric mucosal defenses,maintain the integrity of the mucosal barrier,promote ulcer healing and reduce the relapse.