In the present study, we aimed to explore the mechanism of Rhinoceros Horn and Rehmannia Decoction in treating systemic lupus erythematosus (SLE). First, the active ingredients and their targets of the Chinese medicine components of Rhinoceros Horn and Rehmannia Decoction were searched through TCMSP, TCMID, and BATMAN-TCM databases, and then the drug targets were summarized. Then the disease targets of SLE were retrieved from CTD, OMIM, and TCMIP databases, and the intersection of drug targets and disease targets was analyzed. Cytoscape 3.7.1 software was used to construct a drug-component target-disease network. The protein-protein interaction (PPI) network of therapeutic targets was constructed on the String platform, and its key modules and hub genes were screened. GO and KEGG enrichment analyses were performed in the DAVID database. A total of 22 active ingredients, 209 drug targets, 284 disease targets, and 59 therapeutic targets were screened out. Drug-component-target-disease and PPI network analysis yielded core active ingredients, such as quercetin, kaempferol, and baicalein, and core targets, such as PTGS2, CASP3, MMP9, AKT1, JUN, CXCL8, FOS, and TP53. It mainly involves TNF, PI3K Akt, Toll-like receptor, T cell receptor, and apoptosis signal pathways. It can be seen that Rhinoceros Horn and Rehmannia Decoction may play the role of anti-inflammation, inhibition of abnormal immune response, and apoptosis by regulating inflammation, immunity, and apoptosis signaling pathways. It has the characteristics of multi-center, multi-target, and multi-pathway.
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