The Toll-like Receptor-2/4 Antagonist, Sparstolonin B, and Inflammatory Diseases: A Literature Mining and Network Analysis.

Background: Sparstolonin B (SsnB) is characterized as a new toll-like receptor (TLR)-2/4 antagonist. However, the effects of SsnB on different inflammatory diseases have not been systemically reviewed.

Methods: We investigated the effects of SsnB on inflammatory diseases with data mining and network analysis of literature, including frequency description, cluster analysis, association rule mining, functional enrichment, and protein-protein interaction (PPI) mining.

Results: A total of 27 experimental reports were included. The ARRIVE 2.0 guidelines were used to evaluate the quality of animal studies. Frequency analysis revealed 13 different diseases (cardio-cerebrovascular system diseases account for 23.53%), 12 pharmacological effects (anti-inflammatory effect accounts for 53.85%), and 67 therapeutic targets. The overview of investigation sequence of SsnB studies was depicted by Sankey diagram. Cluster analysis classified the therapeutic targets for SsnB into four main categories: (1) NF-κB; (2) IL-1β, IL-6, and TNF-α; (3) TLR2, TLR4, and MyD88; (4) the other targets. Moreover, the Apriori association discovered two main association pairs: (1) TNF-α, IL-1β, and IL-6 and (2) TLR2, TLR4, and MyD88 (support range 33.33-50%, confidence range 83.33-88.89%). Functional enrichment of the therapeutic targets for SsnB showed that the top enriched items in the biological process were mainly the response to lipopolysaccharide (LPS)/bacterial origin and regulation of cytokine production. Finally, the PPI network and hub gene selection by maximal clique centrality (MCC) algorithm indicated the top ranked proteins were TNF-α, IL-1β, IL-6, AKT1, PPAR-γ, TLR4, CCL2, and TLR2.

Conclusion: These results emphasized the importance of TLR2/TLR4-MyD88-NF-κB-IL-1β/IL-6/TNF-α pathways as therapeutic targets of SsnB in inflammatory diseases.