Preventive effect of dioscin against monosodium urate-mediated gouty arthritis through inhibiting inflammasome NLRP3 and TLR4/NF-κB signaling pathway activation: an in vivo and in vitro study.

Monosodium urate (MSU)-mediated inflammation is closely related to gouty arthritis (GA). Dioscin, an active ingredient, has been reported to possess anti-inflammatory property. Nevertheless, the role of dioscin in GA and the underlying mechanism have not been fully understood. In the present study, we investigated the anti-inflammatory effect of dioscin on MSU-induced GA through in vivo and in vitro experiments. Histopathological analysis showed that dioscin alleviated the severity of GA concomitant with the lowered uric acid and creatinine levels. Moreover, the increasing IL-1ß, IL-6, and TNF-α levels induced by MSU were decreased via administration of dioscin in mice and human synoviocytes. Western blotting results suggested that dioscin inhibited the activation of NLRP3 through down-regulating the protein expressions of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), cleaved-caspase-1, as well as IL-1ß. In addition, TLR4, myeloid differentiation primary response gene 88 (MyD88), p-IKKß, p-p65, and NF-κB p65 in nuclei levels were significantly reduced by dioscin. Importantly, dioscin remarkably lowered the NF-κB p65-DNA activity in MSU-treated mice utilizing electrophoretic mobility shift assay (EMSA) analysis. Taken together, dioscin had a protective effect against MSU-initiated inflammatory response via repressing the production of inflammatory cytokines and the activation of inflammasome NLRP3 and TLR4/NF-κB signaling pathway. The above findings revealed that dioscin could be a potential drug for the treatment of GA.

Higher 25-hydroxyvitamin D level is associated with increased risk for Behçet's disease.

BACKGROUND & AIM: Previous studies showed a vitamin D deficiency in patients with Behçet's disease, suggesting potential benefits of vitamin D supplementation in the prevention and treatment of Behçet's disease. Interpretation of these studies may be limited by reverse causality or confounding bias. We aim to determine the causal association between serum 25-hydroxyvitamin D [25(OH)D] and the risk of Behçet's disease by Mendelian randomization. METHODS: An allele score formed by four variants (rs2282679, rs10741657, rs12785878 and rs6013897) that were associated with serum 25(OH)D level, was examined using data of genome-wide association study (GWAS) on 999 Behçet's disease and 4417 healthy individuals of Chinese ancestry and validated using data of GWAS on 1215 Behçet's disease and 1278 controls of Turkish ancestry. The primary outcome was the risk of Behçet's disease, evaluated by an inverse variance weighted average of the associations with genetically determined 25(OH)D levels. RESULTS: The inverse variance weighted estimate showed that genetically increased 25(OH)D level was associated with a higher risk of Behçet's disease. In the Chinese cohort, the odds ratio for Behçet's disease in one standard deviation increase of natural log-transformed 25(OH)D level was 3.82 (95% CI: 1.27-11.42). Data from Turkish cohort confirmed the association with Behçet's disease (OR, 95% CI: 4.18, 1.15-15.12). In overall combination of Chinese and Turkish cohorts, the odds ratio for Behçet's disease per standard deviation increase of natural log-transformed 25(OH)D level was estimated to be 3.96 (95% CI: 1.72-9.13; P = 0.001). No significant evidence of pleiotropy and heterogeneity was detected. CONCLUSIONS: On the basis of evidence in 7909 human beings, this study provides the newest indication that a lifelong higher 25(OH)D level is associated with an increased risk of Behçet's disease. Special attention should be paid to the potential harm of long-term or high-dose use of vitamin D supplements in clinical practice.