OBJECTIVE: To probe into the mechanism of synergistic effect and toxicity reduction of processing semen crotonis pulveratum by using network pharmacology. METHODS: The components and targets of croton and semen crotonis pulveratum were obtained and screened by integrative pharmacology-based research platform of traditional Chinese medicine（TCMIP） V2.0. Pharmacokinetic and toxicological parameters of Croton were obtained by admetSAR-2.0. Protein-protein interaction network of common targets of croton and semen crotonis pulveratum

and specific targets of croton was constructed by STRING 11.0. Kyoto encyclopedia of genes and genomes（KEGG） enrichment analysis were performed by DAVID. Cytoscape 3.8.0 was used to construct the component-target-pathway network and perform network topology analysis. RESULTS: There were 6 common components and 202 common targets in croton and semen crotonis pulveratum. There were 31 specific components and 107 specific targets in croton. The common components of croton and semen crotonis pulveratum could pass through the blood brain barrier and be absorbed by human small intestine. The pharmacodynamics of croton involved nicotine addiction

GABAergic synapse and Rap1 signaling pathway. The toxicity of croton involved fatty acid metabolism and PPAR signaling pathway. The mechanism of processing semen crotonis pulveratum may be related to nervous system pathways such as amphetamine addiction and long-term potentiation. CONCLUSIONS: Processing semen crotonis pulveratum has synergistic effect and toxicity reduction

which is related to multiple targets and pathways. To explore the predicted targets and pathways is helpful to explain the mechanism of processing semen crotonis pulveratum.