Abstract
Background: Lamiophlomis rotata (LR) showed favorable clinical effect and safety on rheumatoid arthritis (RA), but its active ingredients and mechanisms against RA remain unknown. The aim of this work was to explore the active ingredients and mechanisms of LR against RA by network pharmacology.Methods: Compounds from LR were identified using literature retrieval and screened by absorption, distribution, metabolism, excretion, and toxicity (ADMET) evaluation. Genes related to the selected compounds or RA were identified using public databases, and the overlapping genes between compounds and RA target genes were identified using Venn diagram. Then, the interactions network between compounds and overlapping genes was constructed, visualized, and analyzed by Cytoscape software. Finally, pathway enrichment analysis of overlapping genes was carried out on Database for Annotation, Visualization, and Integrated Discovery (DAVID) platform.Results: A total of 148 compounds in LR were identified, and ADMET screen results indicated that 67 compounds exhibited good potential as active ingredients. A total of 90 compounds-related genes and 1,871 RA-related genes were identified using public databases, and 48 overlapping genes between them were identified. Cytoscape results suggested that the active ingredients and target genes of LR against RA consisted of 23 compounds and 48 genes, and luteolin and AKT1 were the uppermost active ingredient and hub gene, respectively. DAVID results exhibited that the mechanisms of LR against RA were related to 34 signaling pathways, and the key mechanism of LR against RA might be to induce apoptosis of synovial cells by inactivating PI3K-Akt signaling pathway.Conclusion: The active ingredients and mechanisms of LR against RA were firstly investigated using network pharmacology. This work provides scientific evidence to support the clinical effect of LR on RA, and a research basis for further expounding the active ingredients and mechanisms of LR against RA.
Highlights
Rheumatoid arthritis (RA), a chronic autoimmune disease, can cause cartilage and bone damage as well as disability
A total of 148 compounds in Lamiophlomis rotata (LR) were identified by literatures retrieval, and the names, molecular formulas of these compounds are listed in Supplementary Table S1
The results suggested that the therapeutic effect of LR on RA was directly related to the 23 compounds and 48 genes
Summary
Rheumatoid arthritis (RA), a chronic autoimmune disease, can cause cartilage and bone damage as well as disability. RA is characterized by joint inflammation, but is more like a syndrome that consists of extra-articular manifestations, such as rheumatoid nodules, pulmonary involvement or vasculitis, and systemic comorbidities (Smolen et al, 2016). Because inflammation is the main driving factor to cause clinical symptoms, joint damage, disability, and comorbidity in RA patients, anti-inflammation is a key therapeutic strategy (Smolen et al, 2007). For the past few years, TCM has been increasingly important strategy for treatment of RA in China due to its good therapeutic effect and low toxic side effects. Lamiophlomis rotata (LR) showed favorable clinical effect and safety on rheumatoid arthritis (RA), but its active ingredients and mechanisms against RA remain unknown. The aim of this work was to explore the active ingredients and mechanisms of LR against RA by network pharmacology
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