Bioinformatics-based Identification of the Mechanism Whereby Astragalus Membranaceus Inhibits Inflammation and Autophagy in Lupus Nephritis

Background. Lupus nephritis (LN) is an autoimmune disease, and effective treatment can improve the prognosis of patients. Several studies have demonstrated that Astragalus membranaceus can effectively suppress the progression of LN, but the underlying mechanism is still unclear. Thus, this study aimed to investigate the mechanism whereby Astragalus membranaceus exerts this therapeutic effect against LN. Method. Astragalus targets and LN-related targets were obtained from the TCMSP database and WGCNA analysis, respectively. Then we obtain the compound targets and constructed the protein interaction network of the compound targets. The top 10 core targets were identified. And We have validated it. We performed GO and KEGG enrichment analyses on the compound targets to identify the functional and genomic pathways enriched among these targets. Molecular docking of Astragalus membranaceus with the core targets was performed . Result. We identified 214 AM targets and 102 LN-related targets. Among them, we obtained 10 core targets, IL-1β, EGF, CCND1, CASP3, STAT1, PTGS2, and PPARγ were found to have high diagnostic values for LN. In the validation dataset GSE99339, all the core targets were significantly expressed, except for EGF deletion. The results of the KEGG enrichment analysis showed that 7 out of 23 valid targets were significantly enriched in the mitogen-activated protein kinase pathway (p=1.14E-05). The molecular-docking results showed that AM with IL-1β, CASP3, STAT1, and PPARγ had good binding properties. Conclusion. The therapeutic effect of AM against LN might be related to suppression of inflammation and autophagy, and the bioinformatics-based results presented here provide a theoretical basis for the clinical application of AM in LN.