Abstract
BACKGROUND: Herba Siegesbeckiae (HS, Xixiancao in Chinese) is widely used to treat inflammatory joint diseases such as rheumatoid arthritis (RA) and arthritis, and its molecular mechanisms and active ingredients have not been completely elucidated. METHODS: In this study, the small molecule ligand library of HS was built based on Traditional Chinese Medicine Systems Pharmacology (TCMSP). The essential oil from HS was extracted through hydrodistillation and analyzed by Gas Chromatography-Mass Spectrometer (GC-MS). The target of RA was screened based on Comparative Toxicogenomics Database (CTD). The key genes were output by the four algorithms' maximum neighborhood component (MNC), degree, maximal clique centrality (MCC), and stress in cytoHubba in Cytoscape, while biological functions and pathways were also analyzed. The key active ingredients and mechanism of HS and essential oil against RA were verified by molecular docking technology (Sybyl 2.1.1) in treating RA. The interaction between 6 active ingredients (degree ≥ 5) and CSF2, IL1β, TNF, and IL6 was researched based on the software Ligplot. RESULTS: There were 31 small molecule constituents of HS and 16 main chemical components of essential oil (relative content >1%) of HS. There were 47 chemical components in HS. Networks showed that 9 core targets (TNF, IL1β, CSF2, IFNG, CTLA4, IL18, CD26, CXCL8, and IL6) of RA were based on Venn diagrams. In addition, molecular docking simulation indicated that CSF2, IL1β, TNF, and IL6 had good binding activity with the corresponding compounds (degree > 10).The 6 compounds (degree ≥ 5) of HS and essential oil had good interaction with 5 or more targets. CONCLUSION: This study validated and predicted the mechanism and key active ingredients of HS and volatile oil in treating RA. Additionally, this study provided a good foundation for further experimental studies.