Caffeic Acid Attenuates Monosodium Urate Crystal-Induced Gouty Arthritis in Rats: Experimental Evaluation and Molecular Docking Analysis with NLRP3

CONTEXT: Gouty arthritis is an inflammatory joint disorder associated with elevated uric acid levels and deposition of monosodium urate (MSU) crystals in the joints. Although existing treatments can control uric acid levels and inflammation, there is continued interest in identifying naturally occurring compounds with potential anti-inflammatory and antioxidant properties. Caffeic acid is a naturally occurring phenolic compound with reported antioxidant and anti-inflammatory activities; however, its effects in MSU crystal-induced gouty arthritis have not been sufficiently characterised. Therefore, this study was undertaken to investigate the protective effects of caffeic acid in experimental gouty arthritis and to explore its potential interaction with the NLRP3 protein using molecular docking. OBJECTIVE: The present study investigated the anti-gout potential of caffeic acid in an MSU crystal-induced gouty arthritis rat model and explored its potential interaction with the NLRP3 protein through molecular docking. METHODS: Twenty-four female Wistar rats were randomly divided into four groups (n = 6): normal control, disease control, caffeic acid-treated (50 mg/kg, orally), and standard allopurinol-treated (10 mg/kg, orally). Hyperuricemia was induced using potassium oxonate followed by MSU crystal injection in all groups except normal control. Total duration of experiment was 30 days. Body weight, paw volume, serum inflammatory cytokines, renal function biomarkers, radiographic changes, and histopathological alterations were evaluated at the end of experiment. Molecular docking was performed to assess the interaction of caffeic acid with the NLRP3 protein. RESULTS: Caffeic acid significantly reduced paw edema and improved body weight compared with the disease control group (p < 0.05). Treatment decreased the serum inflammatory cytokines, uric acid, creatinine, and urea levels (p < 0.001), while improving radiographic and histopathological features of gouty arthritis. Molecular docking demonstrated favorable binding of caffeic acid with the NLRP3 protein (binding affinity: -6.8 kcal/mol), suggesting a potential interaction with inflammasome-associated pathways. CONCLUSION: Caffeic acid exhibited anti-inflammatory, antihyperuricemic, and renoprotective effects in experimental gouty arthritis. Molecular docking suggested a potential interaction between caffeic acid and NLRP3; however, direct experimental validation of NLRP3 inflammasome activation or inhibition was not performed in the present study.