Exploratory study on the efficacy of Lingze mixture in gouty arthritis rats and preliminary analysis of its potential mechanisms via transcriptome sequencing

Lingze mixture (LM), a traditional Chinese herbal formula, has demonstrated clinical efficacy in treating gouty arthritis (GA). However, its pharmacological mechanisms remain largely unexplored. This study aimed to conduct an exploratory investigation into the anti-inflammatory effects of LM in a GA rat model and to preliminarily identify potential signaling pathways involved through transcriptome analysis. A rat GA model was induced by monosodium urate (MSU) injection. Animals were treated with LM at low, medium, or high doses, with etoricoxib as a positive control. Synovial inflammation was assessed histologically (H&E staining). Protein expression of TLR4, MyD88, and NF-κB was detected by immunohistochemistry (IHC). To generate mechanistic hypotheses, RNA sequencing (RNA-seq) was performed on synovial tissues from the blank, model, and medium-dose LM groups. LM treatment significantly attenuated MSU-induced synovitis and dose-dependently reduced the protein levels of TLR4, MyD88, and NF-κB. Transcriptome analysis revealed significant enrichment of the TLR4/MyD88/NF-κB and MAPK signaling pathways in the model group. Notably, medium-dose LM treatment appeared to modulate these pathways, along with alanine, aspartate, and glutamate metabolism. Our findings confirm the anti-gout efficacy of LM in vivo and provide preliminary evidence suggesting its action may be associated with the modulation of the TLR4/MyD88/NF-κB pathway. This study offers valuable mechanistic clues and a foundation for further in-depth investigation into LM's mode of action.