Mechanisms of rehmannioside A against systemic lupus erythematosus based on network pharmacology, molecular docking and molecular dynamics simulation

Abstract Background The effect of rehmannioside A (RA) on systemic lupus erythematosus (SLE) is not clear and needs further study. Methods SLE-related targets were obtained from the DisGeNet and GeneCards databases, while RA-related targets were obtained from the SwissTarget and SuperPred databases. A protein-protein interaction network of potential targets was constructed using the String platform. After selecting the potential targets, GO and KEGG enrichment analyses were performed via the R packages. The relationships between RA and various core targets were assessed via molecular docking. Molecular dynamics simulation was conducted for optimal core protein–compound complexes obtained by molecular docking. Results The top 5 targets in the ranking of degree value were HSP90AA1, HIF1A, PIK3CA, MTOR, and TLR4. GO functional enrichment analysis revealed that 715 biological processes, 18 cellular components and 72 molecular functions were enriched while KEGG pathway enrichment analysis revealed 128 enriched signaling pathways. Molecular docking showed that RA had the highest binding affinity for MTOR, suggesting that MTOR is a key target of RA against SLE. Molecular dynamics simulations revealed good binding abilities between RA and MTOR. Conclusions RA exerts its effects on SLE through multiple targets and pathways. MTOR may be a key target of RA against SLE.