Investigating the Molecular Mechanism of Xijiao Dihuang Decoction for the Treatment of SLE Based on Network Pharmacology and Molecular Docking Analysis.

objectiveTo elucidate the main mechanism of Xijiao Dihuang decoction (XJDHT) for the treatment of systemic lupus erythematosus (SLE).

methodsTCMSP, BATMAN-TCM, ETCM, and TCMID databases and literature search were used to screen the potential active compounds of XJDHT, and TCMSP and SwissProt databases were searched to predict the targets of the compounds. The targets of SLE were obtained from Genegards, OMIM, and DisGeNET databases, and Venn online platform was used to obtain the intersection targets of XJDHT and SLE. Afterwards, the PPI network was constructed by using the STRING database, and the core targets were identified by network topology analysis. GO and KEGG enrichment analyses were performed through R software, and molecular docking of the top three core targets and their corresponding compounds were accomplished by Autodock Vina and Pymol softwares.

resultsThere were 30 potential active ingredients, 289 potential targets, and 129 intersection targets screened from the above databases. Network topology analysis identified 23 core targets, such as AKT1, TNF, IL6, IL1B, and INS. GO enrichment analysis obtained 2555 terms and mainly clustering on the react to lipopolysaccharide, membrane raft, and ubiquitin-like protein ligase binding. KEGG enrichment analysis obtained 187 signaling pathways, mainly concentrating on the lipid and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, fluid shear stress, and atherosclerosis. Molecular docking verified that the active compounds of XJDHT have the strong binding activity to the core targets.

conclusionThis study preliminarily uncovers the mechanism of XJDHT acting on SLE through a "multicompound, multitarget, and multipathway" manner. XJDHT may achieve the treatment of SLE by inhibiting the proinflammatory factors, inflammatory signal cvtokines, proliferation, injury, and apoptosis processes. In summary, the present study would provide a promising theoretical basis for further clinical and experimental studies.