Allicin Aplealleviates Gouty Arthritis by Regulating the Gut-Joint Axis, Reducing XOD Activity, Inhibiting Oxidative Stress, and Suppressing NLRP3 Inflammasome Activation.

Abstract

Background: Gouty arthritis (GA) is a common joint inflammation closely related to hyperuricemia and urate crystal deposition, and its incidence is on the rise worldwide. Allicin, the primary biologically active component found in freshly crushed garlic extracts, has been reported to possess many beneficial biological functions.

Methods: An animal model was used to evaluate the efficacy of allicin on GA rats, and 16S rRNA sequencing and metabolomics were used to explore changes in the gut microbiota and metabolites. Fecal microbiota transplantation (FMT) and fibroblast-like synoviocytes (FLS) used to explore the mechanism of allicin treating GA.

Results: The results showed that allicin effectively improved the general state of GA rats, inhibited XOD activity, and significantly reduced ROS production and activation of the NLRP3 inflammasome, thereby exerting therapeutic efficacy to protect the kidneys and joints. Examination of the gut microbiota showed that the composition of the gut microbiota of GA rats improved after allicin treatment (increase in Lactobacillus). Metabolomic analysis revealed a significant increase in gut microbial short-chain fatty acid metabolites (butyric acid) following allicin treatment. Furthermore, FMT confirmed that allicin significantly alleviated GA and increased butyric acid content in a gut microbe-dependent manner. Finally, the role of butyric acid in inhibiting ROS generation and NLRP3 inflammasome activation in FLS was elucidated.

Conclusion: This study highlights allicin as a promising therapeutic candidate for GA, emphasizing its potential to inhibit oxidative stress and inflammatory responses by regulating the gut-joint axis.