Active Components and Pharmacological Mechanism of Qingwei Jianpi Pills in Treatment of Infantile Anorexia
Objective:This study aimed to explore the mechanism of Qingwei Jianpi Pills in the treatment of infantile anorexia(IA)based on network pharmacology.Methods:The active components of Qingwei Jianpi Pills and potential targets were analyzed by searching the TCMSP,DisGeNET,DrugBank,GeneCards,NCBI,OMIM,PharmGKB,and TDD databases.The"drug-component-tar-get"and protein-protein interaction(PPI)networks were constructed respectively.Gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed for core targets.Then,molecular docking was performed on the active components of Qingwei Jianpi Pills and core targets.The anorexia model of young rats was es-tablished by feeding rats with special feed.The food intake,body weight,gastric emptying rate,and intestinal propulsion rate were observed.Serum gastrin(GAS),motilin(MTL),and β-endorphin(β-EP)levels were detected by enzyme-linked immunosorbent(ELISA)method.Experimental verification of prediction results based on network pharmacology was carried out.Results:A total of 74 active components of Qingwei Jianpi Pills were screened.The core components included luteolin,quercetin,wogonin,beta-sitos-terol,kaempferol,stigmasterol,berlambine,naringenin,and nobiletin.There were 185 intersection targets corresponding to the treat-ment of IA.Targets with high degree values included cellular tumor antigen p53(TP53),RAC-alpha serine/threonine-protein ki-nase(AKT1),mitogen-activated protein kinase 3(MAPK3),mitogen-activated protein kinase 1(MAPK1),cyclic AMP response el-ement-binding protein 1(CREB1),and gender receptor(ESR1).A total of 2 902 items were obtained from GO functional enrich-ment analysis,and KEGG pathway analysis involved 184 pathways including lipid and atherosclerosis,PI3 K-AKT signaling path-way,chemical carcinogenic-receptor activation,human cytomegalovirus infection,fluid shear stress,and atherosclerosis.The molecu-lar docking results showed that the core components of Qingwei Jianpi Pills,namely R-berlambine(R)-Canadine,had good binding a-bility with the core target CREB1.There was also good binding ability between bicuculline and CREB1,as well as Beta-Carotene and MAPK3.The verification experiment results showed that Qingwei Jianpi Pills could significantly improve the food intake,body weight,gastric emptying rate,and intestinal propulsion rate of young rats with anorexia and increase the levels of GAS,MTL,and β-EP.Con-clusion:Qingwei Jianpi Pills can regulate serum gastrointestinal hormone levels through multiple targets and multiple pathways,there-by enhancing gastric motility and appetite.Its mechanism of action may be related to the regulation of the gastrointestinal tract by its action on MAPK1,MAPK3,and AKT1 signaling pathways.Animal experiments can further verify that it can promote gastrointestinal peristalsis and affect gastrointestinal hormone secretion,providing a reference for the further development of Qingwei Jianpi Pills.
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