The aim of this study was to explore the molecular network regulation mechanism of Coptidis Rhizoma and Scutellariae Radix (SRCR) on treatment of Helicobacter pylori (Hp) associated peptic ulcer (PU) based on network pharmacology and bioinformatics methods,and to screen out the core genes and key microRNAs.Firstly,the main active ingredients and possible targets of SRCR were retrieved through the Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP).GSE70394 gene expression profile data was downloaded from the GEO database.The microarray data of differentially expressed genes in Hp infected human gastric epithelial cells were homogenized by R software,and the volcano map and cluster heat map of differentially expressed genes were drawn.Secondly,STRING database was used to construct the protein interaction network between SRCR component target and Hp- infected human GES cells.The functions of GO and the enrichment of KEGG pathways of the above-mentioned characteristic genes were analyzed by DAVID database.Then,the core genes involved in the treatment of Hp related PU by SRCR were screened out by cytohubba plug-in unit.The key microRNAs regulating the core genes were predicted by using the TargetScan and miRBase databases.Finally,41 active components and 216 potential targets of SRCR were retrieved.The quality of GEO chip data was good.With P< 0.05 and︱logFC︱≥ 2 as the screening conditions,128 differentially expressed genes were obtained,including 77 up-regulated genes and 51 down-regulated genes.127 characteristic gene targets were further obtained for the treatment of HpPU by SRCR.Go analysis of these targets showed that the biological process involved 55 items such as inflammatory response,immune response,etc.Cell components included 11 items such as extracellular space,exosomes,nuclei,etc.Molecular functions included 15 items such as growth factor activity,epidermal growth factor receptor binding,etc.KEGG results showed that 33 signaling pathways,including cytokine receptor interaction pathway,nod like receptor signaling pathway,NF-κB signaling pathway,etc.were closely related to the treatment of Hp related PU by SRCR.Ten core genes regulated by SRCR,such as CXCL8,IL10,IL1B,etc.were screened out by cytohubba.Ten of the most functional microRNAs,such as mir-93-5p,mir-374b-5p,mir-3937,etc.which may be regulated by SRCR,were further screened out.The above results indicate that the treatment of HpPU with SRCR has the characteristics of multi-component,multi-target,and multi-channel synergy.SRCR can exert its therapeutic effect on HpPU by regulating the coding RNA (gene) and non-coding RNA (microRNA).