Conclusion
This research elucidated the pharmacological mechanisms of TFLA against gouty arthritis, implicating various ingredients, targets, and signaling pathways. Animal experiments confirmed TFLA's efficacy in alleviating inflammation in acute gouty arthritis by modulating Toll-like receptor signaling and NLRP3 expression.
Methods
We identified 55 major compounds in TFLA via ultrahigh-performance liquid chromatography connected to quadrupole time-of-flight mass spectrometry (UPLC-TQF-MS/MS). Databases were employed for the prediction of potential targets, followed by PPI network construction as well as GO and KEGG analyses. After network-pharmacology-based analysis, a rat gouty arthritis model was used to validate the anti-inflammatory mechanism of TFLA.
Results
UPLC-TQF-MS/MS and network pharmacology analyses revealed 55 active ingredients and 160 targets of TFLA associated with gouty arthritis, forming an ingredient-target-disease network. The PPI network identified 20 core targets, including TLR2, TLR4, IL6, NFκB, etc. Functional enrichment analyses highlighted the Toll-like receptor signaling pathway as significantly enriched by multiple targets, validated in in vivo experiments. Animal experiments demonstrated that TFLA improved pathological changes in gouty joint synovium, with decreased ankle joint circumference, serum IL6, IL10, and TNFα levels, as well as reduced protein and mRNA expression of NLRP3, TLR2, and TLR4 in ankle joint synovial tissue observed in the middle- and high-dose TFLA and positive control groups compared to the model group (p < 0.05).