复方利通颗粒对高尿酸血症大鼠的降血尿酸作用及其潜在分子机制OA

OBJECTIVE:To evaluate the uric acid-lowering effect and safety of Compound Litong granules in hyperuricemic rats,and to explore its potential molecular mechanisms.METHODS:Sprague-Dawley rats were randomly divided into 7 groups according to serum uric acid levels at day 0:solvent control group,model control group,allopurinol group,benzbromarone group,and three Compound Litong granules 0.6,1.2,2.4 g/kg dose groups,with 13 rats in each group.Except for the solvent control group,rats in all other groups were administered 1.0 g/kg potassium oxonate via intragastric gavage daily in the morning to induce hyperuricemia.Six hours later,rats were gavaged with equal volumes of 0.5％carboxymethylcellulose sodium(CMC-Na),0.027 g/kg allopurinol,0.03 g/kg benzbromarone,and 0.6,1.2,2.4 g/kg Compound Litong ganules,respectively.Rats in the solvent control group received equal volumes of 0.5％CMC-Na in both the morning and afternoon.Body weight was recorded weekly throughout the experiment.On days 30 and 45 after the first administration of the test substances,serum uric acid(UA),alanine aminotransferase(ALT),aspartate aminotransferase(AST),creatinine(CREA),and urea(UREA)levels were measured.Meanwhile,network pharmacology and bioinformatics approaches were used to screen active ingredients and targets,construct a protein-protein interaction(PPI)network,perform Gene Ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses,build a"component-target-pathway"network,and conduct molecular docking verification.RESULTS:On day 45 after administration,the serum uric acid levels in the 0.6,1.2,and 2.4 g/kg Compound Litong granules groups were 92±17,92±14,and 93±17 μmol/L,respectively,which were significantly different from that in the model control group(181±35 μmol/L,P<0.01).Meanwhile,CREA and UREA levels decreased significantly(P<0.05).Network pharmacology analysis indicated that Compound Litong granules exerted its uric acid-lowering effect via 53 active ingredients acting on 171 common target genes.The main active components included quercetin,luteolin,and kaempferol,while PTGS2,RELA,TNF,CASP3,STAT3,and IL-6 were predicted as key core targets,mainly involved in pathways related to lipid and atherosclerosis,insulin resistance,and the AGE-RAGE signaling pathway.Molecular docking results showed good binding affinity between the core components and core targets.CONCLUSION:Compound Litong granules primarily promoted uric acid excretion,supplemented by inhibition of uric acid production.It exerted dual effects of urate-lowering and renal protection by regulating inflammation,oxidative stress,metabolic disorders,and transporters via multi-target,multi-pathway synergistic mechanisms.