Search Results (104)

(1) Background: The urate-lowering effects of three iridoid glycosides, which are paederosidic acid, paederosidic acid methyl ester, and paederoside, isolated from Paederia foetida and the protection they provide against hyperuricemia-induced kidney injury were investigated in a rat model. (2) Methods: A hyperuricemia (HUA) rat model was established in Sprague-Dawley (SD) rats through intraperitoneal potassium oxonate (PO) and intragastrical adenine for 2 weeks. Subsequently, rats in the pharmaceutical intervention groups received corresponding drug treatments at a concentration of 40 mg/kg/day, maintained consistently for 7 days. (3) Results: The results showed that three compounds reduced serum urate (SU), creatinine (CRE), and blood urea nitrogen (BUN) levels and that the urinary excretion levels of uric acid, urine urea nitrogen, and creatinine increased. Furthermore, the administration of three iridoid glycosides enhanced renal filtration capacity, as demonstrated by the elevated 24 h creatinine clearance rate (CCR) and 24 h uric acid clearance rate (CUA); improved the fraction excretion of uric acid (FEUA); and attenuated renal damage. Finally, three iridoid glycosides promoted uric acid excretion in HUA rats by downregulating URAT1 and GLUT9 and upregulating ABCG2, OAT1, and OAT3. Moreover, the molecular docking results further corroborated the finding that the three compounds can bind to multiple sites of the uric acid transporter via hydrogen, P-π, and hydrophobic bonds. (4) Conclusions: The three iridoid glycosides were found to lower SU levels by increasing uric acid excretion. They are promising natural products for the prevention of HUA and HUA-induced kidney injury. Full article

Hyperuricemia (HUA) is a metabolic disorder characterized by excessive uric acid (UA) production and impaired excretion. Goji, as a representative medicinal food, holds significant research and development value, while probiotic fermentation technology is finding increasingly widespread applications in the functional food sector. This study developed a novel goji fermented with three probiotic strains (Lactoplantibacillus plantarum CGMCC8198, Lactococcus lactis LTJ28, and Lactocaseibacillus casei YR2-2) and investigated its anti-HUA effects. Optimal fermentation conditions (7.913 material–liquid ratio, 3.92% inoculation, 7.49 h at 37 °C with 1:1:2 strain ratio) yielded a beverage with enhanced flavor profiles (19 aroma compounds) and high viable counts. In HUA cell models, the 15% fermented goji juice significantly reduced UA levels by 56% (p < 0.01). In potassium oxonate-induced HUA mice, the beverage effectively lowered serum UA, xanthine oxidase activity, and renal function markers (blood urea nitrogen and creatinine, p < 0.0001) while improving hepatic parameters (alanine aminotransferase, aspartate Aminotransferase). The goji-fermented juice significantly reduced the expression of renal UA transporters GLUT9 and URAT1 (p < 0.0001) while improving gut microbiota composition, as evidenced by increased beneficial SCFAs (acetic acid, butyric acid, p < 0.0001) and elevated Lactobacillus abundance 2.14-fold. Our findings demonstrate that this triple-probiotic-fermented goji beverage represents an effective dietary strategy for HUA management by simultaneously inhibiting UA production, enhancing excretion, and restoring gut microbiota homeostasis, providing a scientific basis for developing probiotic-based functional foods against HUA. Full article

This study investigated the role of exosomes in the pathological processes of gouty arthritis (GA), with the aim of clarifying their mechanistic role and pathological significance in the onset and progression of GA. Using a rat model of GA established through potassium oxonate and yeast gavage combined with intra-articular monosodium urate (MSU) injection, we isolated and characterized plasma exosomes using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blotting. Differential exosomal protein expression was analyzed using 4D label-free proteomics technology, followed by GO and KEGG enrichment analyses, and protein–protein interaction (PPI) network construction to identify core targets. In vivo experiments measured the expression levels of CTSD in synovial tissues and joint fluid, as well as HPRT1 in renal tissues, while in vitro experiments involved co-culturing NRK cells with exosomes to validate target protein expression. The results indicated that serum uric acid levels were significantly elevated in the model group (p < 0.01), accompanied by pronounced joint swelling and inflammation. Exosome characterization confirmed their typical bilayer membrane structure and the expression of marker proteins (CD63/TSG101). Proteomic analysis identified 40 differentially expressed proteins (12 upregulated and 28 downregulated) enriched in pathways such as complement and coagulation cascades, autophagy, lysosomal function, and purine metabolism. In vivo and in vitro experiments demonstrated significantly increased CTSD expression (p < 0.05/p < 0.01) and decreased HPRT1 expression (p < 0.05/p < 0.01) in the model group, suggesting that exosomes are involved in the occurrence and development of GA by regulating purine metabolism and lysosomal dysfunction. These findings offer new insights into disease mechanisms and potential therapeutic targets. Full article

Objective: Study the mechanism of ginsenoside Rg₁ in ameliorating hyperuricemia (HUA) induced by high-purine diet. Methods: Rats were randomly divided into groups, and the HUA model was established by administering a high-purine diet containing potassium oxonate combined with yeast. After the experiment, blood was collected via cardiac puncture, and the organ indices of the rats were calculated. Serum biochemical markers including aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), total cholesterol (TC), xanthine oxidase (XOD), creatinine (CREA), uric acid (UA), and blood urea nitrogen (BUN) were measured. Histopathological sections of the kidney and intestine were prepared. Western blot was used to assess the expression levels of intestinal occludin and zonula occludens-1 barrier proteins and key proteins in IL-17/NF-κB inflammatory pathways. After the experiment, fecal samples were collected from the rats. The gut microbiota of HUA-induced rats was analyzed via 16S rRNA sequencing, and the levels of short-chain fatty acids in the fecal samples were quantified using gas chromatography–mass spectrometry. Results: Ginsenoside Rg₁ significantly increased body weight and organ indexes as well as reduced serum levels of BUN, CREA, ALT, AST, XOD, and UA. Pathologic analysis showed that ginsenoside Rg₁ improved renal cell injury, glomerulosclerosis, and renal interstitial fibrosis while restoring intestinal barrier function. Ginsenoside Rg₁ down-regulated the expression of inflammatory proteins and up-regulated the levels of intestinal barrier proteins. The results of 16S rRNA sequencing showed that ginsenoside Rg₁ significantly increased the diversity index of gut microbiota and enhanced the number of beneficial bacteria in HUA rats. Short-chain fatty acids analysis demonstrated that ginsenoside Rg₁ markedly elevated the levels of acetate, propionate, butyrate, and valerate in HUA rats. Conclusions: Ginsenoside Rg₁ ameliorates and treats HUA by improving the composition of intestinal flora and inhibiting the IL-17/NF-κB signaling pathway to reduce inflammatory factors in the intestinal tract in HUA rats. Full article

Background: Hyperuricemia (HUA) is a widespread metabolic disorder that arises from disruptions in purine metabolism, impaired kidney function, or both conditions. FPAW (Phe-Pro-Ala-Trp) is a novel peptide identified from Trachinotus ovatus with great XOD (xanthine oxidase) inhibitory activity (IC₅₀ = 3.81 mM), which can be developed as a potential active ingredient to relieve hyperuricemia. However, it remains unclear whether FPAW alleviates HUA in vivo or not. Methods: In this study, potassium-oxonate-induced hyperuricemic mice were used to evaluate the in vivo anti-hyperuricemic activity of FPAW. Some physiological parameters, such as serum uric acid (SUA), serum creatinine (SCR), blood urea nitrogen (BUN), and the activity of XOD and ADA (adenosine deaminase) in the liver were determined to evaluate the effect of reduced uric acid. The modulations in the gut microbiota and its metabolites (SCFAs) were analyzed by sequencing the V3-V4 region of the 16S rRNA gene and GC-MS in different fecal samples. Molecular docking was used to predict the interactions between the enzymes and FPAW. Results: The results showed that FPAW reduced the levels of serum uric acid, serum creatinine, and blood urea nitrogen, while also suppressing the activity of XOD in the livers of HUA mice. Moreover, the FPAW treatment alleviated gut microbiota dysfunction and increased the production of short-chain fatty acids to protect normal intestinal function and health of the host. Molecular docking simulations revealed that FPAW inhibited XOD activity by entering the hydrophobic channel and interacting with amino acid residues on the surface via hydrogen bonding and hydrophobic interactions. Conclusions: This study provides new candidates for the development of hypouricemic drugs. FPAW exhibited great potential to relieve hyperuricemia of mice induced by diet in the animal experiment. Full article

Background/Objectives: Gouty arthritis (GA) is a chronic inflammatory condition characterized by hyperuricemia and NLRP3 inflammasome activation, leading to joint damage and systemic inflammation. Although allopurinol (ALP), a xanthine oxidase inhibitor, effectively lowers serum urate levels, it has limited anti-inflammatory effects. This study investigated whether combining disulfiram (DSF), a known NLRP3 inflammasome inhibitor, with ALP enhances therapeutic outcomes in a rat model of gout. Methods: Thirty male Albino Wistar rats (150–200 g) were randomly assigned to five groups (n = 6): control, disease control, ALP-treated, DSF-treated, and ALP + DSF combination. Hyperuricemia was induced using potassium oxonate, followed by MSU crystal injection to trigger acute gout. Treatment lasted 30 days. Efficacy was assessed through clinical scoring, paw swelling, serum uric acid levels, ELISA-based cytokine profiling (IL-1β, TNF-α, IL-6), renal function tests, radiography, and histopathology. Results: Combination therapy with ALP + DSF significantly reduced paw swelling (p < 0.05), inflammation index (p < 0.001), serum uric acid (p < 0.001), and pro-inflammatory cytokines compared to monotherapy. Histopathology revealed preserved synovial architecture and reduced inflammatory infiltration. Radiographic imaging showed attenuated soft tissue swelling and joint erosion. Renal function markers were also improved in the combination group. Conclusions: The combination of ALP and DSF provided superior anti-inflammatory and urate-lowering effects compared to individual treatments. These findings support the potential of disulfiram as an adjunct to conventional ULTs in gout management through dual modulation of urate metabolism and inflammasome-driven inflammation. Full article

Objectives: This study investigated the effects and mechanisms of electrolyzed alkaline water (EAW), a type of drinking water, on hyperuricemia (HUA) in mice. Methods: A hyperuricemia model was established by intraperitoneal injection of potassium oxonate and free access to a high-purine diet. EAW was provided ad libitum for 21 days. Results: The results showed that EAW had little impact on the levels of blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, albumin, or xanthine oxidase in mice (p > 0.05). Interestingly, EAW ingestion induced significant reductions in uric acid and creatinine levels (p < 0.05), along with increased urinary uric acid excretion (p < 0.05) and less renal pathological changes in mice. Additionally, EAW upregulated GLUT9 gene expression (p > 0.05) and downregulated URAT1 protein expression. Conclusions: In conclusion, this study demonstrates that EAW promotes uric acid excretion by downregulating URAT1 and GLUT9 protein expression, resulting in a significant reduction in uric acid levels. Full article

Background: Hyperuricemia is a prevalent metabolic disorder characterized by elevated serum uric acid (UA) levels. Methods: In this study, hydrolysate (SPP) derived from silkworm pupae protein was isolated and identified, demonstrating anti-hyperuricemic activity. The research aimed to investigate its anti-hyperuricemic and nephroprotective effects, along with potential mechanisms, through in vitro assays and in vivo experiments using potassium oxonate/hypoxanthine-induced hyperuricemic mice. Results: The SPP exhibited significant xanthine oxidase (XOD) inhibitory activity, with an IC₅₀ value of 7.41 mg/mL. Furthermore, SPP administration effectively reduced serum UA, blood urea nitrogen (BUN), creatinine levels, and renal pro-inflammatory cytokines in hyperuricemic mice. Mechanistic studies revealed that the anti-hyperuricemic effects of SPP may involve XOD inhibition and the modulation of renal UA transporters, specifically upregulating organic anion transporter 1 (OAT1) and ATP-binding cassette subfamily G member 2 (ABCG2) expression. Histopathological analysis and inflammatory cytokine profiling further demonstrated that SPP alleviated renal inflammation and pathological damage. Conclusions: These findings suggest that SPP possesses a notable urate-lowering efficacy and renal protective properties, highlighting its potential as a therapeutic agent for the management and prevention of hyperuricemia (HUA). Full article

This study optimized the proportions of synergistic catalysts to efficiently activate potassium peroxymonosulfate (Oxone), generate more reactive oxygen species, and accelerate the chemical oxidation of silicon carbide (4H-SiC) wafers during chemical–mechanical polishing (CMP) for an improved material removal rate (MRR) and surface quality. The Oxone was activated using ultraviolet (UV) catalysis with a photocatalyst (TiO₂) and transition metal (Fe₃O₄) to enhance the oxidation capacity of the polishing slurry through the production of strong oxidizing sulfate radicals (${\mathrm{S}\mathrm{O}}_4^{·-}$). First, the effects of the TiO₂, Fe₃O₄, and Oxone concentrations on the MRR were studied by conducting multiple single-factor experiments. Next, 4H-SiC wafers were polished using different catalyst combinations to verify the synergistic activation of Oxone by multiple catalysts. Finally, the roughnesses, physical features, and elemental compositions of the wafer surfaces were observed before and after polishing. The results showed that CMP with a TiO₂ concentration of 0.15 wt%, Fe₃O₄ concentration of 0.75 wt%, and Oxone concentration of 48 mM decreased the wafer surface roughness from Sa 134 to 8.251 nm and achieved a maximum MRR of 2360 nm/h, which is significantly higher than that associated with traditional CMP methods. The surface of a 4H-SiC wafer polished using CMP with the optimal catalytic system was extremely smooth with no scratches and exhibited many oxides that reduced its hardness. In summary, the proposed UV-TiO₂-Fe₃O₄-Oxone composite catalytic system for 4H-SiC CMP exhibited significant synergistic enhancements and demonstrated excellent surface quality, indicating considerable potential for the polishing of hard materials. Full article

This study investigated the protective effects of a polyherbal tea (PHT) on intestinal injury in hyperuricemia (HUA) mice and the underlying mechanisms. PHT was orally administered to mice for 49 days, while potassium oxonate and hypoxanthine were administered 7 days after PHT administration and continued for 42 days to cause HUA. Treatment with PHT significantly reduced serum uric acid and blood urea nitrogen levels in HUA mice. It also inhibited liver xanthine oxidase activity and promoted intestinal uric acid excretion through the upregulation of transporters GLUT9 and ABCG2. Intestinal barrier integrity was reinforced, as evidenced by the restoration of the villous structure, reduction in edema, and upregulation of tight junction proteins (occludin, ZO-1) and mucin (MUC2). Moreover, PHT suppressed serum LPS levels and inhibited the NF-κB pathway, leading to a reduction in TNF-α and IL-6 levels in the gut. Gut microbiota analysis revealed PHT reversed dysbiosis, enriching beneficial bacteria like Duncaniella sp. and Heminiphilus faecis. By UPLC–MS analysis, 154 compounds of PHT persisted in the gut, suggesting that these compounds are likely to modulate both intestinal barrier function and gut microbiota. These findings suggest that this PHT may have potential as a functional food for the prevention of hyperuricemia. Full article

Hyperuricemia (HUA), characterized by elevated serum uric acid (UA) levels, is a key risk factor for gout. In human purine metabolism, approximately 70% of UA is excreted via the kidneys, while the remaining 30% is eliminated through the intestines. Thus, the intestinal microbiota plays a crucial role in regulating UA metabolism through the gut–kidney axis. However, the detailed mechanisms by which the microbiota reduces serum UA levels and supports kidney health remain unclear. In this study, researchers investigated the potential of Lacticaseibacillus paracasei LT12, a strain exhibiting xanthine oxidase (XO) inhibition activity and the ability to degrade inosine and guanosine, in reducing UA levels in a hyperuricemia mouse model. Hyperuricemia was induced by gavaging mice with 300 mg/kg of potassium oxonate and hypoxanthine for two weeks. The subsequent 4-week intervention included five groups: a normal control group, a model group, a positive control group receiving allopurinol (5 mg/kg body weight), a low-dose LT12 group (1.5 × 10⁶ CFU/kg), and a high-dose LT12 group (4.5 × 10⁹ CFU/kg). The results demonstrated that L. paracasei LT12 effectively reduced serum UA levels, inhibited serum and hepatic XO activity, regulated renal uric acid transporter proteins (OAT1, URAT1, GLUT9, and ABCG2), and reduced the abundance of the intestinal pathogenic bacterium Corynebacterium stationis in both the low-dose and high-dose groups. Notably, only the high-dose LT12 group significantly increased gut butyrate levels. In conclusion, L. paracasei LT12 shows promise as a potential probiotic strain for ameliorating hyperuricemia. Future human clinical studies are needed to validate its efficacy. Full article

Lychee peel generated during the industrial processing of lychee fruit are currently disposed of as agricultural waste. This study investigates the primary components of lychee peel extract (LPE) and the regulatory mechanisms of LPE on reducing uric acid (UA). Mice were injected with hypoxanthine and potassium oxonate to induce hyperuricemia and concurrently orally administered LPE. The analysis of the LPE composition reveals a predominance of polyphenolic compounds, including (-)-epicatechin, (-)-epigallocatechin, and procyanidin A2. In vitro tests have demonstrated that the LPE significantly inhibits the activity of xanthine oxidase (XOD). In vivo studies showed that LPE can reduce UA levels in hyperuricemia mice. Further mechanistic insights indicate that LPE inhibits hepatic XOD activity, thereby reducing UA synthesis within the organism. It also decreases the protein expression of urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9), which leads to diminished UA reabsorption and increased excretion of UA. Additionally, LPE enhances the activity of superoxide dismutase (SOD) while simultaneously reducing malondialdehyde (MDA) contents, thereby improving antioxidant capacity in mice. Our findings indicate that LPE not only inhibits the production of UA but also promotes its elimination, positioning it as a promising candidate for UA-lowering agents. Full article

A plant-based diet is considered a promising approach for managing hyperuricemia (HUA). This study examined the effects of soy protein and plant-based oils on HUA-induced inflammation and immune dysfunction. Male Wistar rats, induced with HUA using oxonic acid and uric acid (UA), were fed casein or soy protein with palm or safflower oil (2 × 2 factorial design) for 8 weeks. HUA rats had lower serum albumin and T cell percentages in peripheral blood leukocytes (PBLs) and splenocytes, along with increased leukocyte counts and spleen weights, compared to healthy rats (p < 0.05). Soy protein improved HUA-induced reductions in albumin, while safflower-seed oil ameliorated reductions in albumin, plasma interleukin (IL)-4, and T-suppressor splenocytes, and mitigated elevated serum UA, plasma IL-6, and B leukocytes (two-way ANOVA, p < 0.05). In PBL, soy protein alleviated HUA-induced decreases in TNF-α, casein and palm oil increased IL-6, and casein further reduced IFN-γ production. Under Con A stimulation, casein and safflower-seed oil alleviated decreases in IL-6 and IL-10, respectively, while under LPS stimulation, casein further increased TNF-α production. In splenocytes, soy protein and safflower-seed oil reduced HUA-induced increases in TNF-α and increased IL-10, and safflower-seed oil increased IL-6 production. Under Con A stimulation, soy protein and safflower-seed oil reduced TNF-α and increased IL-10 production in splenocytes. The findings suggest that soy protein and safflower-seed oil may counteract HUA-related inflammation, alleviate monocyte activation, and enhance Th2 immune response in HUA. A plant-based diet rich in soy protein and safflower-seed oil may help manage HUA and associated inflammation and immune dysfunction. Full article

Background/Objectives: Current urate-lowering therapies may cause serious side effects in patients. Thus, alternative treatments are needed to regulate uric acid (UA) levels in patients with hyperuricemia associated with kidney injury, and natural antioxidant sources have demonstrated utility in this field. For the first time, our study evaluated the effects of an extract of Dactylopius opuntiae insects on the levels of xanthine oxidase (XO) enzymes and synthetic free radicals in vitro and in vivo. Methods: Insects were bred and collected, and two different extracts (D1 and D2) were obtained. For both extracts, XO inhibition and radical scavenging assays were performed. Subsequently, serum purine levels and renal markers were quantified in male BALB/c mice who received a hyperuricemia induction using potassium oxonate, hypoxanthine, and gentamicin. Results: The D2 extract contained 18,037.7 µg/mL of carminic acid, inhibited 53.2% of XO activity at one concentration, and showed IC50 values of 18,207.8 and 5729.6 µg/mL against ABTS and DPPH radicals, respectively. D2 administration reduced serum UA and creatinine levels and prevented an increase in kidney weight and reduction in renal antioxidant capacity caused by hyperuricemia induction and allopurinol use in mice. Despite the satisfactory antioxidant results obtained in vitro, the D1 extract killed the animal models due to its citric acid content. Conclusions: The D2 insect extract can be used as an effective urate-lowering therapy when the increased level of serum uric acid is due to kidney damage. Full article

Magnetic nanoparticles (MNPs) based on magnetite (Fe₃O₄) are attractive catalyst supports due to their high surface area, easy preparation, and facile separation, but they lack stability in acidic reaction media. The search for MNPs stable in oxidative acidic reaction media is a necessity if one wants to combine the advantages of MNPs as catalyst supports with those of iodine(III) reagents being environmentally benign oxidizers. In this work, immobilized iodophenyl organocatalysts on magnetite support (IMNPs) were obtained by crossed-linking polymerization of 4-iodostyrene with 1,4-divinylbenzene in the presence of MNPs. The obtained IMNPs were characterized by TGA, IR, SEM, STEM, and HAADF to gain information on catalyst morphology, average particle size (80–100 nm), and their core–shell structure. IMNP-catalysts tested in (i) the α-tosyloxylation of propiophenone 1 with meta-chloroperbenzoic acid (m-CPBA) and (ii) in the oxidation of 9,10-dimethoxyanthracene 3 with Oxone^® as the side-oxidant showed a similar performance as reactions using stoichiometric amounts of iodophenyl. The developed IMNPs withstand strong acidic conditions and serve as reusable organocatalysts. They are recyclable up to four times for repeated organocatalytic oxidations with rates of recovery of 80–92%. This is the first example of a—(4-iodophenyl)polystyrene shell—magnetite core-structured organocatalyst withstanding strong acidic reaction conditions. Full article