Potential Molecular Mechanisms of Zhibai Dihuang Wan in Systemic Lupus Erythematosus Based on Network Biology

Abstract

Systemic lupus erythematosus (SLE) is a refractory autoimmune disease. Zhibai Dihuang Wan (ZDW) has frequently been used for treating SLE in China and been proved to have a prominent role in decreasing SLE patients' morality rate. However, the active substances in ZDW and the molecular mechanisms of ZDW in SLE remain unclear. This study identified the bioactive compounds and delineated the molecular targets and potential pathways of ZDW by using a network biology approach. First, we collected putative targets of ZDW based on TCMSP, GeneCards, and STITCH databases and built a network containing the interactions between the putative targets of ZDW and known therapeutic targets of SLE. Then, the key hubs were imported to DAVID Bioinformatics Resources 6.7 to perform gene ontology biological process (GOBP) and pathway enrichment analysis. A total of 95 nodes including 73 putative targets of ZDW were determined as major hubs in terms of their node degree. The results of GOBP and pathway enrichment analysis indicated that putative targets of ZDW mostly were involved in various pathways associated with inflammatory response and apoptosis. More importantly, eleven putative targets of ZDW (CASP3, BCL2, BAX, CYCS, NFKB1, NFKBIA, IL-6, IL-1β, PTGS2, CCL2, and TNF-α) were recognized as active factors involved in the main biological functions of treatment, implying the underlying mechanisms of ZDW acting on SLE. This study provides novel insights into the mechanisms of ZDW in SLE, from the molecular level to the pathway level.