Association between vegetarian diet and gouty arthritis: A retrospective cohort study.

BACKGROUND AND AIMS: A vegetarian diet is rich in vegetables, fruits, and soy products. Although vegetarian diet is beneficial for improving the health outcomes such as body mass index, metabolic syndrome, cardiovascular disease, and mortality rate, the association between a vegetarian diet and gout incidence is not well known. METHODS AND RESULTS: We linked the MJ Health Survey Data and MJ Biodata 2000 with the National Health Insurance Research Database (NHIRD) and the National Registration of Death (2000-2018). Information on the diet was collected from the MJ Health Survey Data, and the incidence of gouty arthritis was confirmed using the NHIRD. The Kaplan-Meier survival curve and log-rank test were used to compare the differences between vegetarian and non-vegetarian participants. Cox regression models were used to estimate the risk of the incidence of gouty arthritis. Among 76,972 participants, 37,297 (48.46%) were men, 2488 (3.23%) were vegetarians and the mean age was 41.65 ± 14.13 years. The mean baseline uric acid level was 6.14 ± 1.65 mg/dL. A total of 16,897 participants developed gouty arthritis, including 16,447 (22.08%) non-vegetarians and 450 (18.9%) vegetarians over a mean follow-up of 19 years. Significant differences were observed in the Kaplan-Meier survival curves between vegetarians and non-vegetarians (log-rank p < 0.001). Vegetarians had a significantly decreased incidence of gouty arthritis compared with non-vegetarians (hazard ratio = 0.87, 95% confidence interval = 0.78-0.98, p = 0.02) after adjusting for potential confounders. CONCLUSION: People with a vegetarian diet had a significantly decreased risk of developing gouty arthritis compared with non-vegetarians in Taiwan.

Palmatine Protects Against MSU-Induced Gouty Arthritis via Regulating the NF-κB/NLRP3 and Nrf2 Pathways.

Purpose: Gouty arthritis could be triggered by the deposition of monosodium uric acid (MSU) crystals. Palmatine (PAL), a protoberberine alkaloid, has been proven to possess compelling health-beneficial activities. In this study, we aimed to explore the effect of PAL on LPS plus MSU crystal-stimulated gouty arthritis in vitro and in vivo. Methods: PMA-differentiated THP-1 macrophages were primed with LPS and then stimulated with MSU crystal in the presence or absence of PAL. The expression of pro-inflammatory cytokines and oxidative stress-related biomarkers and signal pathway key targets were determined by ELISA kit, Western blot, immunohistochemistry and qRT-PCR, respectively. In addition, the anti-inflammatory and antioxidant activities of PAL on MSU-induced arthritis mice were also evaluated. Results: The results indicated that PAL (20, 40 and 80 µM) dose-dependently decreased the mRNA expression and levels of pro-inflammatory cytokines (interleukin-1beta (IL-1ß), IL-6, IL-18 and tumor necrosis factor alpha (TNF-α)). The levels of superoxide dismutase (SOD) and glutathione (GSH) were remarkably enhanced, while the level of malondialdehyde (MDA) was reduced. Western blot analysis revealed that PAL appreciably inhibited NF-κB/NLRP3 signaling pathways through inhibiting the phosphorylation of p-65 and IκBα, blocking the expression of NLRP3, ASC, IL-1ß and Caspase-1, as well as enhancing the antioxidant protein expression of Nrf2 and HO-1. In vivo, PAL attenuated MSU-induced inflammation in gouty arthritis, as evidenced by mitigating the joint swelling, and decreasing the productions of IL-1ß, IL-6, IL-18, TNF-α and MDA, while enhancing the levels of SOD and GSH. Moreover, PAL further attenuated the infiltration of neutrophils into joint synovitis. Conclusion: PAL protected against MSU-induced inflammation and oxidative stress via regulating the NF-κB/NLRP3 and Nrf2 pathways. PAL may represent a potential candidate for the treatment of gouty arthritis.

Tetrahydropalmatine attenuates MSU crystal-induced gouty arthritis by inhibiting ROS-mediated NLRP3 inflammasome activation.

Activation of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome plays a crucial role in the inflammatory responses of monosodium urate (MSU) crystal-induced gouty arthritis. Therefore, the molecular basis of NLRP3 inflammasome is very valuable in developing potential therapeutic drugs for gout. Tetrahydropalmatine (THP), the main active component of the traditional Chinese medicinal herb Corydalis yanhusuo, has shown prominent anti-inflammatory and analgesic activities, but to date, these effects have not been investigated exhaustively on gout. This study indicated that THP attenuated pain and swelling in an MSU-induced acute gout model by decreasing pro-inflammatory cytokine production and inflammatory cell infiltration. THP exerted its actions by suppressing NLRP3 inflammasome activation and subsequent formation of caspase-1. Furthermore, results showed that THP alleviated MSU-induced reactive oxygen species (ROS) generation, upstream of NLRP3 inflammasome activation, by an increase in the activities of antioxidant enzymes both in vitro and in vivo. In conclusion, our study suggests that THP suppressed ROS-mediated NLRP3 inflammasome activation in MSU-induced inflammatory responses, which highlights its therapeutic potential in gouty arthritis.

Total glucosides of paeony protects THP-1 macrophages against monosodium urate-induced inflammation via MALAT1/miR-876-5p/NLRP3 signaling cascade in gouty arthritis.

BACKGROUND: Monosodium urate (MSU)-mediated inflammatory response is a crucial inducing factor in gouty arthritis. Here, we explored the underlying mechanism of total glucosides of paeony (TGP) in MSU-induced inflammation of THP-1 macrophages in gouty arthritis. METHODS: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect cell viability. Enzyme-linked immunosorbent assay (ELISA) was utilized to measure the production of interleukin 1ß (IL-1ß) and tumor necrosis factor α (TNF-α). Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were conducted to determine RNA and protein expression. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull down assay were used to confirm the interaction between miR-876-5p and MALAT1 or NLR family pyrin domain containing 3 (NLRP3). RESULTS: MSU-induced damage and inflammatory response in THP-1 macrophages were alleviated by the treatment of TGP in a dose-dependent manner. Overexpression of NLRP3 or MALAT1 reversed the protective effects of TGP in MSU-induced THP-1 macrophages. The binding relation between miR-876-5p and MALAT1 or NLRP3 was identified in THP-1 macrophages. MALAT1 up-regulated the expression of NLRP3 by sponging miR-876-5p in THP-1 macrophages. TGP suppressed MSU-induced inflammation in THP-1 macrophages through regulating MALAT1/miR-876-5p/NLRP3 axis. TGP suppressed MSU-induced activation of TLR4/MyD88/NF-κB pathway through regulating MALAT1/miR-876-5p/NLRP3 axis. CONCLUSION: In conclusion, TGP suppressed MSU-induced inflammation in THP-1 macrophages through regulating MALAT1/miR-876-5p/NLRP3 axis and TLR4/MyD88/NF-κB pathway, suggesting that TGP was a promising active ingredient for gouty arthritis treatment.

MiR-223-3p and miR-22-3p inhibit monosodium urate-induced gouty inflammation by targeting NLRP3.

BACKGROUND: MicroRNAs (miRNAs) have been shown to play a crucial role in inflammation regulation; however, their relationship with inflammation in acute gouty arthritis has not been fully elucidated. Herein, we conducted a study to explore the regulatory roles of miR-223-3p and miR-22-3p in gouty-associated inflammation. METHODS: In vitro and in vivo experiments were conducted to examine the molecular mechanisms of miRNA regulation in gouty inflammation. Dual-luciferase reporter assay was used to verify the direct target of miR-223-3p and miR-22-3p. RESULTS: We found that miR-223-3p and miR-22-3p interacted with the 3' untranslated region segment of NLRP3 (nucleotide-binding domain leucine-rich repeat [NLR] and pyrin domain containing receptor 3) and inhibited its expression. A decreased expression of miR-223-3p and miR-22-3p was observed in both mice air pouch synovium and phorbol myristrate acetate-treated THP-1 cells stimulated with monosodium urate (P < .05). Compared with the negative control group, NLRP3 expression at the transcript and protein level in miR-223-3p and miR-22-3p overexpression group significantly decreased after 6 hours of monosodium urate treatment in vivo and in vitro (P < .05). The results of the dual-luciferase reporter assay demonstrated that miR-223-3p and miR-22-3p directly targeted NLRP3. CONCLUSION: The findings of the present study show that miR-223-3p and miR-22-3p can reduce the inflammatory effects of gout by inhibiting the expression of NLRP3.

Management and Cure of Gouty Arthritis.

Gout is the most common inflammatory arthritis in the United States. Gouty arthritis is associated with significant morbidity and mortality and is caused by hyperuricemia. Gout is effectively managed and potentially cured by decreasing the overall urate burden with serum urate-lowering therapy. When serum urate is maintained at less than 6.0 mg/dL urate deposition is resolved and gout can be cured. Unfortunately, owing to a lack of physician monitoring and dose escalation the majority of patients do not achieve these urate levels.

Human recombinant interleukin-38 suppresses inflammation in mouse models of local and systemic disease.

Interleukin (IL)-38 belongs to the IL-1 family and is part of the IL-36 subfamily due to its binding to the IL-36 Receptor (IL-1R6). In the current study, we assessed the anti-inflammatory properties of IL-38 in murine models of arthritis and systemic inflammation. First, the anti-inflammatory properties of mouse and human IL-38 precursors were compared to forms with a truncated N-terminus. In mouse bone marrow derived dendritic cells (BMDC), human and mouse IL-38 precursors with a truncation of the two N-terminal amino acids (3-152) suppressed LPS-induced IL-6. Recombinant human IL-38 (3-152) was further investigated for its immunomodulatory potential using four murine models of inflammatory disease: streptococcal cell wall (SCW)-induced arthritis, monosodium urate (MSU) crystal-induced arthritis, MSU crystal-induced peritonitis, and systemic endotoxemia. In each of these models IL-38 significantly reduced inflammation. In SCW and MSU crystal-induced arthritis, joint swelling, inflammatory cell influx, and synovial levels of IL-1ß, IL-6, and KC were reduced by 50% or greater. These suppressive properties of IL-38 in SCW-induced arthritis were independent of the anti-inflammatory co-receptor IL-1R8, as IL-38 reduced arthritis equally in IL-1R8 deficient and WT mice. In MSU crystal-induced peritonitis, IL-38 reduced hypothermia, while plasma IL-6 and KC and peritoneal KC levels were reduced by 65-70%. In the LPS endotoxemia model, IL-38 pretreatment reduced systemic IL-6, TNFα and KC. Furthermore, in ex vivo cultured bone marrow, LPS-induced IL-6, TNFα and KC were reduced by 75-90%. Overall, IL-38 exhibits broad anti-inflammatory properties in models of systemic and local inflammation and therefore may be an effective cytokine therapy.

Icariin alleviates MSU-induced rat GA models through NF-κB/NALP3 pathway.

Icariin (ICA) has anti-inflammatory effects in some diseases, but its role in gouty arthritis (GA) is not clear. This study investigated the effects of ICA in monosodium urate (MSU)-induced GA rat models. GA rat models were induced by MSU, and co-treated with ICA of low-dose (20 mg/kg), medium-dose (40 mg/kg), and high-dose (80 mg/kg), respectively. The ankle swelling rates, haematoxylin-eosin (HE) staining changes, inflammatory factors (interleukin (IL)-1ß, IL-6, tumour necrosis factor-α (TNF-α)) and prostaglandin E2 (PGE2 ) levels in synovial tissues were detected. The antioxidants levels in rat serum, and NF-κB pathway-related proteins and NALP3 inflammasome expressions in synovial tissues were also analysed. In cell experiments, chondrocytes were co-treated with different concentrations of ICA (1, 5, 10 µmol/L) on the basis of MSU. The activities and inflammatory cytokines, hydroxyproline (Hyp) and glycosaminogly (GAG) expressions in chondrocytes were measured. In rat experiments, MUS increased the ankle swelling rates, promoted inflammatory cells infiltration, and increased IL-1ß, IL-6, TNF-α, PGE2 levels in synovial tissues, which were all alleviated by ICA. Moreover, ICA also suppressed nuclear translocation of NF-κB pathway-related proteins and reduced the expression of NALP3 inflammasome in rat models. As for cell experiments, ICA decreased the activity, inflammatory cytokines and GAG levels, and suppressed nuclear translocation of NF-κB pathway-related proteins of MSU-treated chondrocytes. In general, medium and high concentrations of ICA showed good effects. ICA has an inhibitory effect in MSU-induced rat GA models through NF-κB/NALP3 pathway, which may provide a direction for the treatment of GA. SIGNIFICANCE: Icariin (ICA) has anti-inflammatory effects in some diseases, but its role in gouty arthritis (GA) is not clear. This study excogitated that monosodium urate (MSU) increased the ankle swelling rates of rats, promoted inflammatory cells infiltration, and increased cytokines levels in synovial tissues, which were all alleviated by ICA. In related mechanism, we found that ICA might exert the catabatic functions through the NF-κB/NALP3 pathway. The findings of this study clarified that ICA may provide a direction for the treatment of patients with GA and illustrated the relevant underlying mechanism of its role.

Apamin from bee venom suppresses inflammation in a murine model of gouty arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Bee venom (BV) has been used for the treatment of inflammatory diseases, such as rheumatoid arthritis, and for the relief of pain in traditional oriental medicine. AIM OF STUDY: The aim of this study was to determine the anti-inflammatory effect of BV on monosodium urate (MSU)-induced gouty arthritis in a mouse model. MATERIALS AND METHODS: To develop a mouse model of acute gouty arthritis, 4 mg 50 µL-1 of MSU crystal suspension was injected intradermally into the right paw. After MSU crystal injection, we evaluated inflammatory cytokine production in mice of the BV-treated (0.5 and 1 mg kg-1 body weight) and apamin (APM)-treated (0.5 and 1 mg kg-1 body weight) groups. The positive control group was administered a colchicine (1 mg kg-1 body weight) injection with MSU crystals. RESULTS: BV and APM treatment suppressed inflammatory paw edema in MSU-administered mice. It also exerted anti-inflammatory effects in mice with gouty arthritis by inhibiting proinflammatory cytokine production and inflammasome formation. Interestingly, MSU crystal formation was decreased by BV and APM treatment. CONCLUSIONS: These results suggest that the APM from BV might be useful for the treatment of gouty arthritis due to its anti-inflammatory activities.

Recent approaches to gout drug discovery: an update.

INTRODUCTION: Inflammation induced by urate deposition in joints causes gout. Healthy individuals maintain serum levels of urate by balancing urate production/excretion, whereas a production/excretion imbalance increases urate levels. Hyperuricemia is diagnosed when the serum urate level is continuously above 7 mg/dl as the solubility limit, and urate accumulates in the kidneys and joints. Because hyperuricemia increases the risk of gout, therapies aim to eliminate urate deposition to prevent gouty arthritis and kidney injury. AREAS COVERED: This review discusses the mechanism underlying hyperuricemia with respect to urate production and urate transport, along with urate-lowering therapeutics, including urate synthesis inhibitors, uricolytic enzymes, and uricosuric agents. The authors asses published data on relevant commercial therapy development projects and clinical trials. EXPERT OPINION: Available treatment options for hyperuricemia are limited. Allopurinol, a urate synthesis inhibitor, is generally administered at a reduced dosage to patients with renal impairment. Some URAT1 inhibitors have an unfavorable side effect profile. A promising strategy for treatment is the use of uricosuric agents that inhibit transporters (e.g. URAT1, URATv1/GLUT9, OAT10) which reabsorb urate from the urine.

Inhibition of Hyperuricemia and Gouty Arthritis in BALB/c Mice Using Copper Oxide Nanoparticles.

Nanoparticles are known for their unique properties and are being utilized in various disciplines of sciences. Their nanosize enables them to higher exposure and higher availability when given orally. Gout is an inflammatory disease caused by deposition of monosodium urate (MSU) crystal deposition into the joints. The objective of this study was to evaluate the effects of copper oxide nanoparticles on hyperuricemia and gouty arthritis in mice. In this research, synthesized copper oxide nanoparticles of size ranging from 30 to 50 nm were administered orally to mice having gouty arthritis and hyperuricemia. Various biochemical markers were conducted to determine the effects of copper oxide nanoparticles. It was observed that the mice treated with CuO NPs at various concentrations showed a significant (0.001) decrease in the serum uric acid levels in comparison with the negative control. Furthermore, creatinine levels were also normal in comparison with the control mice. Measurement of synovial joints also revealed that mice administered with CuO NPs had reduced inflammation of synovial joints in comparison with the negative control. From this research, it was concluded that copper oxide nanoparticles have potential in the treatment of hyperuricemia and gouty arthritis by decreasing serum uric acid and inflammation in synovial joints.

Paeonol ameliorates monosodium urate-induced arthritis in rats through inhibiting nuclear factor-κB-mediated proinflammatory cytokine production.

Moutan Cortex has been widely used to treat various types of arthritis in traditional Chinese medicine. Paeonol is isolated as an active ingredient from Moutan Cortex. However, the effect and potential mechanism of paeonol on gouty arthritis have not been evaluated. In this study, rats were treated intragastrically with paeonol for consecutive 7 days. On Day 5, rats were intra-articularly injected with monosodium urate (MSU) crystals in the ankle joints to induce MSU-induced arthritis (MIA). Paw volume was detected at various time points. Gait score was measured at 24 hr after MSU crystal injection. Ankle joints were collected for evaluation of histological score and expression of proinflammatory cytokines using hematoxylin and eosin staining and immunohistochemistry staining, respectively. Nuclear level of nuclear factor (NF)-κBp65 in synovial tissues was analyzed by western blot assay. NF-κB DNA-binding activity was measured by enzyme linked immunosorbent assay. Paeonol markedly lowered the paw volume, gait score, and histological score in MIA rats. Mechanistically, paeonol markedly reduced the expression of TNF-α, IL-1ß, and IL-6 in synovial tissues of MIA rats. In addition, the elevated level of p65 in nucleus and NF-κB DNA-binding activity in synovial tissues of MIA rats were reduced significantly by paeonol treatment. These findings suggest that paeonol exerts anti-inflammatory effect in MIA rats through inhibiting expression of proinflammatory cytokines and NF-κB activation.

Mechanistic insight into the attenuation of gouty inflammation by Taiwanese green propolis via inhibition of the NLRP3 inflammasome.

Dysregulation of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome is involved in many chronic inflammatory diseases, including gouty arthritis. Activation of the NLRP3 inflammasome requires priming and activation signals: the priming signal controls the expression of NLRP3 and interleukin (IL)-1ß precursor (proIL-1ß), while the activation signal leads to the assembly of the NLRP3 inflammasome and to caspase-1 activation. Here, we reported the effects of the alcoholic extract of Taiwanese green propolis (TGP) on the NLRP3 inflammasome in vitro and in vivo. TGP inhibited proIL-1ß expression by reducing nuclear factor kappa B activation and reactive oxygen species (ROS) production in lipopolysaccharide-activated macrophages. Additionally, TGP also suppressed the activation signal by reducing mitochondrial damage, ROS production, lysosomal rupture, c-Jun N-terminal kinases 1/2 phosphorylation and apoptosis-associated speck-like protein oligomerization. Furthermore, we found that TGP inhibited the NLRP3 inflammasome partially via autophagy induction. In the in vivo mouse model of uric acid crystal-induced peritonitis, TGP attenuated the peritoneal recruitment of neutrophils, and the levels of IL-1ß, active caspase-1, IL-6 and monocyte chemoattractant protein-1 in lavage fluids. As a proof of principle, in this study, we purified a known compound, propolin G, from TGP and identified this compound as a potential inhibitor of the NLRP3 inflammasome. Our results indicated that TGP might be useful for ameliorating gouty inflammation via inhibition of the NLRP3 inflammasome.

15d-PGJ2-loaded nanocapsules ameliorate experimental gout arthritis by reducing pain and inflammation in a PPAR-gamma-sensitive manner in mice.

Gout arthritis (GA) is a painful inflammatory disease in response to monosodium urate (MSU) crystals in the joints. 15deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is a natural activator of PPAR-γ with analgesic, anti-inflammatory, and pro-resolution properties. Thus, we aimed to evaluate the effect and mechanisms of action of 15d-PGJ2 nanocapsules (NC) in the model of GA in mice, since a reduction of 33-fold in the dose of 15d-PGJ2 has been reported. Mice were treated with 15d-PGJ2-loaded NC, inert NC, free 15d-PGJ2 (without NC), or 15d-PGJ2-loaded NC+ GW9662, a PPAR-γ inhibitor. We show that 15d-PGJ2-loaded NC provided analgesic effect in a dose that the free 15d-PGJ2 failed to inhibiting pain and inflammation. Hence, 15d-PGJ2-loaded NC reduced MSU-induced IL-1ß, TNF-α, IL-6, IL-17, and IL-33 release and oxidative stress. Also, 15d-PGJ2-loaded NC decreased the maturation of IL-1ß in LPS-primed BMDM triggered by MSU. Further, 15d-PGJ2-loaded NC decreased the expression of the components of the inflammasome Nlrp3, Asc, and Pro-caspase-1, as consequence of inhibiting NF-κB activation. All effects were PPAR-γ-sensitive. Therefore, we demonstrated that 15d-PGJ2-loaded NC present analgesic and anti-inflammatory properties in a PPAR-γ-dependent manner inhibiting IL-1ß release and NF-κB activation in GA. Concluding, 15d-PGJ2-loaded NC ameliorates MSU-induced GA in a PPAR-γ-sensitive manner.

Prophylaxis of acute flares when initiating febuxostat for chronic gouty arthritis in a real-world clinical setting.

OBJECTIVE: Flare prophylaxis is recommended during urate-lowering therapy (ULT) despite lack of proven benefit especially when initiating febuxostat. We investigated if colchicine or steroids administration during initiation of febuxostat for chronic gouty arthritis reduces the frequency and/or severity of acute gout flares. METHODS: Patients with confirmed diagnosis of gout starting febuxostat were retrospectively studied. Frequency, severity, and length of flares were analyzed. Assessment of severity based on a visual analog scale (VAS). RESULTS: Two hundred and seventy-three patients were studied. The mean dose of colchicine and steroids was 0.53 ± 0.15 mg PO QD and 7.55 ± 1.30 mg prednisone equivalent PO QD; while the duration was 6.13 ± 1.14 and 6.20 ± 1.36 months, respectively. Subjects treated with colchicine and steroids suffered fewer total flares (0.30, 0.96 vs 2.47, p = .000), fewer flares from 0 to 3 months (0.26, 0.71 vs 1.72, p = .000), less severe flares assessed by VAS than those without prophylactic therapy (3.65, 3.49 vs 5.54, p = .000). Both total flares (p = .003) and flares from 0 to 3 months (p = .008) of the colchicine group were fewer than the steroids group. There were no significant differences in length of flares among groups (p = .815). Both colchicine and steroids were well tolerated. CONCLUSION: The use of colchicine or steroids prophylaxis reduces the frequency and severity of acute gout flares during initiation of febuxostat for chronic gouty arthritis. Colchicine is superior to steroids in flares prophylaxis. Prophylactic therapy with colchicine 0.5 mg PO QD or steroids 7.5 mg prednisone equivalent PO QD for 6 months is suggested.

The tyrosine kinase inhibitor imatinib mesylate suppresses uric acid crystal-induced acute gouty arthritis in mice.

Gouty arthritis is caused by the deposition of monosodium urate (MSU) crystals in joints. Despite many treatment options for gout, there is a substantial need for alternative treatments for patients unresponsive to current therapies. Tyrosine kinase inhibitors have demonstrated therapeutic benefit in experimental models of antibody-dependent arthritis and in rheumatoid arthritis in humans, but to date, the potential effects of such inhibitors on gouty arthritis has not been evaluated. Here we demonstrate that treatment with the tyrosine kinase inhibitor imatinib mesylate (imatinib) can suppress inflammation induced by injection of MSU crystals into subcutaneous air pouches or into the ankle joint of wild type mice. Moreover, imatinib treatment also largely abolished the lower levels of inflammation which developed in IL-1R1-/- or KitW-sh/W-sh mice, indicating that this drug can inhibit IL-1-independent pathways, as well as mast cell-independent pathways, contributing to pathology in this model. Imatinib treatment not only prevented ankle swelling and synovial inflammation when administered before MSU crystals but also diminished these features when administrated after the injection of MSU crystals, a therapeutic protocol more closely mimicking the clinical situation in which treatment occurs after the development of an acute gout flare. Finally, we also assessed the efficiency of local intra-articular injections of imatinib-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles in this model of acute gout. Treatment with low doses of this long-acting imatinib:PLGA formulation was able to reduce ankle swelling in a therapeutic protocol. Altogether, these results raise the possibility that tyrosine kinase inhibitors might have utility in the treatment of acute gout in humans.

Gouty Arthritis: A Review of Acute Management and Prevention.

Gouty arthritis is one of the most common rheumatic diseases. The clinical burden of gouty arthritis has historically been well recognized; however, gout is often misdiagnosed and mismanaged. The prevalence of gout is rising and is likely attributed to several factors including increased incidence of comorbidities, lifestyle factors, and increased use of causative medications. With the increasing prevalence, there have been several innovations and evidence-based updates related to the diagnosis and management of gout. Acute gouty arthritis should be treated with nonsteroidal antiinflammatory drugs (NSAIDs), colchicine, or corticosteroids, or a combination of two agents. Xanthine oxidase inhibitor therapy remains the consensus first-line treatment option for the prevention of recurrent gout. Add-on therapies that reduce serum urate concentration include traditional uricosuric agents and a novel uric acid reabsorption inhibitor. Prophylaxis of acute gout with NSAIDs, colchicine, or corticosteroids is universally recommended when initiating any urate-lowering therapy in order to prevent acute gouty arthritis for a period of at least 6 months. In this review, we discuss the epidemiology and risk factors for gouty arthritis and evaluate diagnostic strategies and therapeutic regimens for the management of gout, including a new drug approval.

Traditional Chinese Medicine Formula "Xiaofeng granules" suppressed gouty arthritis animal models and inhibited the proteoglycan degradation on chondrocytes induced by monosodium urate.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiaofeng Granules (XF) is a kind of granules prepared by the famous traditional Chinese medicine formula for its efficiency in treating gouty diseases. AIM OF THE STUDY: We investigated the relevance between XF that made from Modified simiaowan (MSW) as the anti-gouty arthritis drugs and protective mechanisms for cartilage matrix in order to provide the evidence for new drug application. MATERIALS AND METHODS: In the present study, we evaluated the anti-gouty arthritis activity of XF in rats and rabbits models induced by MSU together with chondrocytes focusing on the link to proteoglycan degradation in vitro studies. RESULTS: The results demonstrated that XF significantly reduced the swelling rate and attenuated the pathological changes in joints. The XF-containing serum were used medicated serum in cellular experiments. The in vitro data were in accordance with the in vivo results, showing that the constituents in XF-containing serum had obvious inhibitory effects on the activation of pro-inflammatory mediators in chondrocytes. Moreover, XF-containing serum substantially inhibited MSU-induced expression of glycosaminoglycans(GAG) and hydroxyproline(Hyp), and up regulated proteoglycan, which might be associated with the regulation of the balance of MMP-3/TIMP-1and ADAMTS-4/TIMP-3 inchondrocytes. CONCLUSION: In conclusion, XF that made from MSW showed obvious effects on acute gouty arthritis, which also provided an effective protection on cartilage matrix degradation.

PPAR-γ agonist pioglitazone affects rat gouty arthritis by regulating cytokines.

The objective was to study peroxisome proliferator-activated receptor gamma (PPARγ) agonist pioglitazone regulation effect and its mechanism of expression of cytokines on acute gouty arthritis synovial in rats. Rats with unilateral ankle were injected with artificial monosodium urate (MSU) crystals to make the acute gouty arthritis model. Taking the synovium 48 h after the injection of MSU and using RT-PCR, we assessed the effect of pioglitazone (20 mg·kg(-1)·day(-1), oral administration) on synovial expression, by detecting tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interferon-γ (IFN-γ). The pioglitazone treatment group showed synovial expression of TNF-α, and IFN-γ was significantly lower than in the control group; the inhibition rates were 78.5 and 60.4%. The IL-1 expression difference was not statistically significant between the two groups. Pioglitazone has anti-inflammatory effects on acute gouty arthritis by inhibiting the expression of TNF-α and IFN-γ.