Resveratrol alleviates MSU-induced gouty arthritis in rats through inhibition of HIF-1α- and NLRP3-derived IL-1ß secretion in macrophages.

Gouty arthritis is an acute and chronic joint inflammatory joint disease characterized by the deposition of monosodium urate (MSU) crystals in joints and periarticular tissues. Resveratrol (3, 5, 4-trihydroxy-trans-stilbene, RV), a natural polyphenolic compound, has anti-inflammatory and antioxidant properties. The purpose of this study was to investigate the effect of resveratrol on rats with gouty arthritis and its molecular mechanism. THP-1-derived macrophages were induced by lipopolysaccharide (LPS) and MSU to create an in vitro gout cell inflammation model, and rats were injected with MSU crystals into the right ankle joint for an in vivo acute gouty arthritis model. We investigated the anti-inflammatory properties of resveratrol using these in vitro and in vitro models. Our findings suggested that resveratrol effectively reduced ankle swelling and synovial inflammation in a dose-dependent manner in rats with acute gouty arthritis, with almost the same effect as colchicine treatment. In MSU-treated THP-1-derived macrophages, resveratrol inhibited NLRP3 inflammasome activation and IL-1ß secretion. Furthermore, resveratrol and the HIF-1α inhibitor PX478 both inhibited the expression of the NLRP3 inflammasome, IL-1ß, and HIF-1α. This study demonstrated that resveratrol significantly improved the symptoms of acute gouty arthritis and its potential mechanism may be IL-1ß reduction via HIF-1α modulation and inhibition of NLRP3 inflammasome activation. Our study might offer a novel sight for the treatment of gouty arthritis.

A metabonomic study to explore potential markers of asymptomatic hyperuricemia and acute gouty arthritis.

BACKGROUND: Acute gouty arthritis (AGA) is a metabolic disease with acute arthritis as its main manifestation. However, the pathogenesis of asymptomatic hyperuricemia (HUA) to AGA is still unclear, and metabolic markers are needed to early predict and diagnose. In this study, gas chromatography (GC)/liquid chromatography (LC)-mass spectrometry (MS) was used to reveal the changes of serum metabolites from healthy people to HUA and then to AGA, and to find the pathophysiological mechanism and biological markers. METHODS: Fifty samples were included in AGA, HUA, and healthy control group, respectively. The metabolites in serum samples were detected by GC/LC-MS. According to the statistics of pairwise grouping, the statistically significant differential metabolites were obtained by the combination of multidimensional analysis and one-dimensional analysis. Search the selected metabolites in KEGG database, determine the involved metabolic pathways, and draw the metabolic pathway map in combination with relevant literature. RESULTS: Using metabonomics technology, 23 different serum metabolic markers related to AGA and HUA were found, mainly related to uric acid metabolism and inflammatory response caused by HUA/AGA. Three of them are completely different from the previous gout studies, nine metabolites with different trends from conventional inflammation. CONCLUSIONS: In conclusion, we analyzed 150 serum samples from AGA, HUA, and healthy control group by GC/LC-MS to explore the changes of these differential metabolites and metabolic pathways, suggesting that the disease progression may involve the changes of biomarkers, which may provide a basis for disease risk prediction and early diagnosis.