Search Results (54)

(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 abnormal purine metabolism and/or reduced uric acid (UA) excretion. Chicory (Cichorium intybus L.), recognized in Traditional Chinese Medicine, is noted for its anti-HUA effects, particularly in enhancing intestinal UA excretion, though the underlying mechanisms remain unclear. Studies indicate that disruptions in gut microbiota and its metabolites are associated with HUA, and chicory has been demonstrated to ameliorate gut microbiota dysbiosis. Among gut microbiota-derived metabolites, butyrate, a short-chain fatty acid, plays a crucial role in gut functions and is linked to HUA. Therefore, butyrate may be pivotal in elucidating the mechanism by which chicory promotes intestinal UA excretion. This study aims to investigate whether chicory facilitates intestinal UA excretion through gut microbiota-derived butyrate and to elucidate the underlying mechanism. We employed an integrated methodology combining network biology with the NHANES database analysis to explore the pathological relationship between butyrate and HUA. Our findings were subsequently validated through animal experiments. We administered chicory to rats with HUA to ascertain whether butyrate serves as the key gut microbiota metabolite through which chicory promotes intestinal UA excretion. Furthermore, we utilized western blotting to assess the expression of core targets within the PPARγ-ABCG2 pathway associated with butyrate under conditions where animals received butyrate supplements and PPARγ agonists separately. The network biology indicates that butyrate is a crucial short-chain fatty acid influencing HUA. Analyses of NHANES data and animal experiments further confirm a significant negative correlation between butyrate and serum uric acid (SUA) levels. HUA rats exhibited intestinal barrier damage, impaired intestinal UA excretion, reduced butyrate levels, and decreased expression of PPARγ and ABCG2 proteins. Intervention with chicory in HUA rats repaired intestinal barrier damage, enhanced intestinal UA excretion, and increased both butyrate levels and the expression of PPARγ and ABCG2 proteins. Similarly, interventions with butyrate supplements or PPARγ agonists in HUA rats effectively promoted intestinal UA excretion and increased the expression of PPARγ and ABCG2 proteins. This study demonstrates that butyrate is a key metabolite produced by gut microbiota, through which chicory regulates gut microbiota to enhance intestinal UA excretion. The underlying mechanism involves the activation of the PPARγ-ABCG2 pathway, which is facilitated by elevated butyrate levels in the intestine. Full article

Objectives: Hyperuricemia (HUA) is a metabolic disorder linked to serious complications, yet current treatments face safety limitations. This study aimed to identify novel probiotic strains from Chinese Baijiu fermentation grains with dual-action mechanisms for HUA management—direct uric acid (UA) reduction and gut microbiota restoration. Methods: Two Lactiplantibacillus plantarum strains (LTJ1/LTJ48) were screened for purine/nucleoside degradation using HPLC. Their efficacy was evaluated in HepG2 cells and HUA mice. Key assessments included UA levels, renal/hepatic markers (AST, CRE, BUN), ADA/XOD activity, UA transporter expression (URAT1, GLUT9, ABCG2), and 16S rRNA-based microbiota analysis. Results: LTJ1/LTJ48 degraded >97% of purines/nucleosides in vitro. In HUA mice, they reduced serum UA by 31.0% (LTJ1) and 51.5% (LTJ48), improved renal/hepatic function, and suppressed ADA activity. They modulated UA transporters and restored gut microbiota. Conclusions: LTJ1/LTJ48 exhibit multi-target HUA alleviation via purine degradation, ADA inhibition, UA transporter regulation, and microbiota remodeling, offering a safer probiotic-based alternative to conventional therapies. Their translational potential warrants further clinical exploration. Full article

Hyperuricemia (HUA), a metabolic disorder characterized by elevated serum uric acid (UA) levels, often leads to renal and hepatic complications. This study evaluated the synergistic effects of Pediococcus acidilactici GQ01, a probiotic strain isolated from naturally fermented wolfberry, in combination with a complex (T) composed of buckwheat-fermented postbiotics, collagen peptide and multiple medicinal food blends in a murine HUA model. The combination therapy (T + GQ01) not only significantly reduced serum UA levels more effectively than T or GQ01 alone but also demonstrated superior inhibition of XOD activity and enhanced ADA activity, both of which are key regulators of purine metabolism. Additionally, T + GQ01 ameliorated kidney injury, as evidenced by reduced serum CRE and BUN levels, and improved liver function, indicated by decreased ALT and AST activities. Histopathological analysis further confirmed the protective effects of T + GQ01 on renal and hepatic tissues. Moreover, T + GQ01 modulated intestinal flora composition, promoted beneficial genera such as Weissella and Bacteroides, and enhanced the production of SCFAs, particularly propionic and butyric acids, which play critical roles in maintaining intestinal health. These findings suggest that the cocktail-like microecological regulator combining P. acidilactici GQ01, buckwheat-fermented postbiotics, collagen peptide and multiple medicinal food blends represents a promising therapeutic strategy for HUA by targeting multiple metabolic pathways, underscoring its potential as a novel intervention for HUA and its complications. 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

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: Hyperuricemia (HUA) has become the second largest metabolic disease after diabetes, and has become a major public health problem. The ELITEA compound tea extract can effectively reduce the serum uric acid level in HUA rat models. In this study, the mechanism of ELITEA compound tea on HUA was analyzed through serum untargeted metabolomics analysis. Methods: The rat model of HUA was established by feeding rats with a high uric acid diet. A total of 24 male SD rats were divided into a blank control group, a hyperuricemia model group, and an ELITEA compound tea prevention experimental group. UPLC-MS/MS was used to detect changes in metabolites in the blood of the three groups of rats, in order to identify potential biomarkers and study the mechanism of ELITEA compound tea in preventing HUA. Results: The ELITEA compound tea exhibited significant preventive effects on HUA rats. The analysis results showed that after ELITEA combined tea intervention, the 257 metabolites downregulated in the HUA model group showed an upward trend. Meanwhile, the 115 metabolites upregulated in the HUA model group showed a decreasing trend. Six main enrichment pathways were obtained, including arginine biosynthesis, histidine metabolism, pyrimidine metabolism, tryptophan metabolism, vitamin B6 metabolism, arginine and proline metabolism. Conclusions: ELITEA compound tea can effectively reduce the serum uric acid levels in HUA model rats. Based on the in-depth analysis of untargeted metabolomics, ELITEA compound tea mainly regulates the arginine biosynthesis pathway by modulating three important metabolites, arginine, glutamate, and ornithine, to reduce serum uric acid. Full article

Background: Coix seed oil (YRO), rich in unsaturated fatty acids, has emerged as a promising intervention for hyperuricemia (HUA) due to its potential to alleviate oxidative damage and support organ health. Methods: The fatty acid composition of YRO was determined by gas chromatography–mass spectrometry (GC-MS). A HUA mouse model was established, and serum markers and hepatic enzymes were evaluated. Renal mitochondrial function was assessed using immunohistochemistry and immunofluorescence, and urate transporter expression, along with key signaling proteins, was quantified by Western blot analysis. Additionally, gut microbiota composition was analyzed, and non-targeted metabolomics was performed to observe alterations in serum lipid metabolites. Results: YRO significantly reduced serum uric acid (UA) levels and normalized hepatic enzyme activities. Histological evaluation revealed less tissue damage in both the kidney and the intestine. In the kidney, YRO improved mitochondrial function and supported antioxidant defenses via regulation of Keap1/Nrf2 signaling. In the intestine, YRO enhanced barrier integrity by increasing ZO-1, Occludin, and Claudin-1 expression. Moreover, YRO modulated gut microbiota by increasing beneficial bacteria (Muribaculaceae, Prevotellaceae UCG-001, Lachnospiraceae_ NK4A136_group, Akkermansia) while suppressing harmful species (Bacteroides, Dubosiella). Lipid metabolomics indicated a restoration of phospholipid balance through modulation of the PI3K/AKT/mTOR pathway. Conclusions: YRO supported metabolic health by promoting UA homeostasis, enhancing mitochondrial function, reinforcing antioxidant capacity, and maintaining gut integrity. These findings suggest that coix seed oil could serve as a nutritional supplement in managing HUA and related metabolic disturbances. 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

Hyperuricemia (HUA) is a metabolic disease caused by disrupted purine metabolism, characterized by abnormally elevated uric acid (UA) levels. Stachydrine, an alkaloid in natural foods, exhibits multiple biological activities. This study aimed to evaluate the effects of stachydrine on alleviating HUA. An HUA mouse model was established through high-nucleoside diet induction, and stachydrine’s effects on UA levels and renal injury were investigated. Our findings revealed that stachydrine enhanced uric acid excretion by upregulating ATP-binding cassette subfamily G member 2 (ABCG2). Furthermore, stachydrine mitigated HUA-induced renal inflammation, mitochondrial oxidative stress and apoptosis. Mechanistically, stachydrine facilitated the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) by downregulating Kelch-like ECH-associated protein 1 (Keap1), subsequently activating the Keap1/Nrf2 signaling pathway and alleviating local oxidative stress. This study demonstrated the UA-lowering and renoprotective effects of stachydrine, suggesting its potential as a functional food ingredient for mitigating HUA. 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

Background: At present, there are still limitations and challenges in the treatment of hyperuricemia (HUA). Mendelian randomization (MR) has been widely used to identify new therapeutic targets. Therefore, we conducted a systematic druggable genome-wide MR to explore potential therapeutic targets and drugs for HUA. Methods: We integrated druggable genome data; blood, kidney, and intestinal expression quantitative trait loci (eQTLs); and HUA-associated genome-wide association study (GWAS) data to analyze the potential causal relationships between drug target genes and HUA using the MR method. Summary-data-based MR (SMR) analysis and Bayesian colocalization were used to assess causality. In addition, we conducted phenome-wide association studies, protein network construction, and enrichment analysis of significant targets to evaluate their biological functions and potential side effects. Finally, we performed drug prediction and molecular docking to identify potential drugs targeting these genes for HUA treatment. Results: Overall, we identified 22 druggable genes significantly associated with HUA through MR, SMR, and colocalization analyses. Among them, two prior druggable genes (ADORA2B and NDUFC2) reached statistically significant levels in at least two tissues in the blood, kidney, and intestine. Further results from phenome-wide studies revealed that there were no potential side effects of ADORA2B or NDUFC2. Moreover, we screened 15 potential drugs targeting the 22 druggable genes that could serve as candidates for HUA drug development. Conclusions: This study provides genetic evidence supporting the potential benefits of targeting 22 druggable genes for HUA treatment, offering new insights into the development of targeted drugs for HUA. 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