Study On The Intervention And Metabolic Mechanism Of Modified Huanglian Decoction On Peptic Ulcer Model Mice

Objective:In this study,the 1H NMR metabolomics analysis of the gastric mucosa and duodenum tissue samples of peptic ulcer model mice,combined with histopathological observation,was conducted to explore the repair effect of Modified Huanglian Decoction on the mucosa damage of peptic ulcer mice and the metabolic response mechanism of Modified Huanglian Decoction on the gastric mucosa and duodenum tissue.Methods:40 SPF KM mice were randomly divided into blank group,model group,western medicine group and Chinese medicine group according to random number table method.Except for the normal group,peptic ulcer model was induced by binding cold stress method in the other three groups.After successful modeling,mice in the traditional Chinese medicine group were treated with Modified Huanglian decoction,while mice in the western medicine group were treated with esomeprazole magnesium enteric-coated tablet aqueous solution.The pathological changes of gastric mucosa and duodenum were observed by HE staining.Ultra-high performance liquid mass spectrometry(UHPLMS)was used to detect the effective components in the decoction of modified coptis decoction.Using 1H NMR technique in nuclear magnetic resonance(NMR)metabolomics detection,through the analysis of the pattern recognition method metabolites qualitative metabolic profile differences between groups,and select different metabolites,through the analysis of the online website(https://www.metaboanalyst.ca/)to find related metabolic pathways.Results:The histopathology showed that the epithelial structure of gastric mucosa in blank group was complete,the glands in lamina propria were compact and the cells were orderly arranged.In model group,the upper layer and lamina propria of gastric mucosa were damaged with large defects,and capillary bleeding and inflammatory cell infiltration were observed in the glands.The gastric mucosa of mice in the traditional Chinese medicine group and the western medicine group was intact,with clear and orderly glands and clear cell structure.No inflammatory cell infiltration,no obvious congestion and edema were observed between the two groups.In the upper layer of duodenal mucosa of mice in blank group,model group and traditional Chinese medicine group,intestinal villi were arranged neatly and protruded into the intestinal cavity.In the lamina propria,the glands are dense and cells are closely arranged.The duodenal tissue structure is complete.The glands are compact and clear,and the cells are neatly arranged,without obvious inflammatory cells.The intestinal villi of the duodenal mucosa of mice in the western medicine group were sparse,disorderly and detached,and the upper cortex was separated from the lamina propria,but the glands were closely arranged.UHPLC-MS results showed that a total of 56 components were found in the decoction of flavorized Coptidis decoction,including 8 components of Coptidis,including Coptidine,Evoidolide,Berberine,Epicerberine,Tetrandrine,Rhizophorine,Magnolinine,Phellodone and Phellodolide.There are 7 species in Pinellia tuber,respectively:valeraldehyde oxime,2-aminobutyric acid,1-octene,tempartic acid,citral,urine black acid,gingerolenone;There are 5 kinds of cassia twig,respectively:cassia aldehyde,coumarin,cassia acetate ester,calamin,β-cubeb;There are 7 species in Codonopsis,which are L-proline,isoleucine,aspartic acid,glutamic acid,methionine,phenylalanine and L-arginine.There are four kinds of jujube,respectively:malic acid,aximinobin,N-methyl-nothyline,betulinic acid;There were 7 species of dried ginger,which were β-cairnene,1,8-eucalyptin,α-gingerene,β-sweet myrrh,6-gingerone,6gingerol,hexahydrocurcumin.There are 6 kinds of glycyrrhizin,respectively:glycyrrhizin,glycyrrhizin,isoglycyrrhizin,glycyrrhizin,neoglycyrrhizin,isoglycyrrhizin;There are 6 species in the herb,respectively:apigenin,luteolin,kaempferin,quercetin,quercitrin,isoquercitrin;There are 6 species in Paeonia lactiflora,respectively:paeonol,paeoniflorin,paeoniflorin,oxypaeoniflorin,benzoylpaeoniflorin,gallic paeoniflorin.1H NMR results showed that 18 metabolic markers were found in the gastric mucosa,which were related to 15 metabolic pathways,namely:D-glutamine and D-glutamate metabolism;Metabolism of alanine,aspartic acid and glutamate;Glutathione metabolism;Glyceride metabolism;Glycine,serine and threonine metabolism;Carbamyl-tRNA biosynthesis;Phosphoinositol metabolism;Cysteine and methionine metabolism;Arginine biosynthesis;Glycerolipid metabolism;Metabolism of arginine and proline;Pyruvate metabolism;Glyoxylic acid and dicarboxylic acid metabolism;Phosphatidylinositol signaling pathway;Galactose metabolism.Nineteen metabolites were found in the duodenum,which were related to 12 metabolic pathways:synthesis and degradation of ketone bodies;Biosynthesis of phenylalanine,tyrosine and tryptophan;Phenylalanine metabolism;Glyceride metabolism;Niacin and niacinamide metabolism;Metabolism of alanine,aspartic acid and glutamate;Butyrate metabolism;Glycine,serine,threonine metabolism;Pyruvate metabolism;Glycerol phospholipid metabolism;Degradation of valine,leucine and isoleucine;Sphingolipid metabolism.Conclusion:Modified Huanglian Decoction can promote gastric mucosa repair in mice with peptic ulcer.It was found that the decoction of Modified Huanglian decoction had anti-oxidation,anti-inflammatory and anti-tumor effects by UHLMS.Through the expression of 1H NMR metabolites,it was found that Modified Huanglian Decoction could affect the expression of metabolites through metabolic pathways such as neurotransmitter metabolism,amino acid metabolism,REDOX reaction and glucose metabolism,which is the possible mechanism of Modified Huanglian Decoction in promoting ulcer healing,and other related molecular response mechanisms still need to be further studied.