Hyperuricemic Model Research Articles

Lacticaseibacillus Casei JS-2 from ‘Jiangshui’ Reduces Uric Acid and Modulates Gut Microbiota in Hyperuricemia

Lacticaseibacillus casei (JS-2) is a novel probiotic isolated from “Jiangshui”, a kind of traditional folk fermented food, which has a significant effect on hyperuricemia (HUA). In vitro experimental results showed that JS-2 has a high degradation ability and selectivity for uric acid (UA). The animal test results indicated that after two weeks of treatment, JS-2 could significantly reduce the level of UA in the serum of HUA quails (p < 0.01), and its effect is almost equivalent to that of the positive drug control group, benzbromarone. Further, after JS-2 treatment, the level of xanthine oxidase in quail serum decreased significantly. Analysis data of quail fecal metabolomics results showed that JS-2-altering metabolites were involved in amino acid, purine, and lipid metabolism. To investigate the mechanism underlying JS-2-mediated UA degradation in the quail model of HUA, 16S rRNA gene sequencing was conducted. It was found that the structure and function of the gut microbiota were restored after JS-2 intervention, and the abundance of short-chain fatty acid (SCFA)-producing bacteria (g__Ruminococcus_torques_group and g__Butyricicoccus) and bacteria with UA degradation capacity (g__unclassified_f__Lachnospiraceae and g__Negativibacillus) increased significantly; intestinal SCFAs, especially propionic acid, increased accordingly. These experimental data suggest that the beneficial effects of JS-2 may derive from changes in the gut microbiome, altering host–microbiota interactions, reducing UA levels by increasing UA excretion, and reducing absorption. These findings provided new evidence that JS-2 has the potential to be used as a naturally functional food for the prevention of HUA.

Spatiotemporal landscape of kidney in a mouse model of hyperuricemia at single-cell level.

Serum uric acid is an end-product of purine metabolism. Uric acid concentrations in excess of the physiological range may lead to diseases such as gout, cardiovascular disease, and kidney injury. The kidney includes a variety of cell types with specialized functions such as fluid and electrolyte homeostasis, detoxification, and endocrine functions. Two-thirds of uric acid is excreted through kidney, however, the exploration of markers and new therapeutic targets in renal tissue of hyperuricemia is still lacking. Single-cell and spatial omics techniques represent major milestones in life sciences. The combined measurement of the physical structure and molecular characteristics of tissues facilitates the exploration of the pathophysiological processes underlying disease development and the discovery of possible therapeutic targets. Here, the spatiotemporal atlas of hyperuricemic nephropathy was investigated using single-cell RNA sequencing, spatial transcriptomics, spatial proteomics, and spatial metabolomics in a urate oxidase knockout mouse model. Several emerging targets and pathways especially ribosome and metabolism related to uric acid excretion were discovered and will be investigated further in studies on lowering uric acid.

Therapeutic Effects of Tea Polyphenols on Renal Damage Induced by High Uric Acid.

Hyperuricemia (HUA) is a condition characterized by excessive uric acid production and/or inadequate uric acid excretion due to abnormal purine metabolism in the human body. Uric acid deposits resulting from HUA can lead to complications such as renal damage. Currently, drugs used to treat HUA lack specificity and often come with specific toxic side effects. This study aimed to investigate the renal protective effects of an optimized tea polyphenol formula and allopurinol in a rat model of hyperuricemia following renal resection. The goal was to explore the mechanisms underlying these effects. Initially, a blend was formulated based on the distinctive functions of catechins, thearubigins, tea polysaccharides, and theanine. Orthogonal experiments were then employed to select a rational combination. A 5/6 renal resection rat model was successfully established, and the animals were fed a 2% oxonic acid diet to induce hyperuricemia. Urinary protein content was measured using the biuret method, and serum levels of uric acid, creatinine, and urea nitrogen were determined biochemically. Kidney pathology was examined through HE staining and renal tubulointerstitial pathological scoring. The expression of α-SMA, CD34, PCNA, and TGF-β in renal tissue was detected using immunohistochemistry. Apoptosis of renal tubular epithelial cells was assessed using the TUNEL method. Hyperuricemia markedly worsens renal damage in rats following nephrectomy, while tea polyphenols demonstrate the ability to reduce levels of blood uric acid, urea nitrogen, creatinine, and urinary protein. Additionally, tea polyphenols enhance smooth muscle proliferation in renal glomerular arterioles, prevent the loss of interstitial capillaries, alleviate apoptosis of renal tubular epithelial cells, promote their proliferation, and reduce interstitial fibrosis. A significant improvement in the severity of renal damage is observed in rats subjected to nephrectomy combined with hyperuricemia, and this effect surpasses that of allopurinol. Tea polyphenols could effectively alleviate renal damage in rats with nephrectomy combined with hyperuricemia. They demonstrate high cost-effectiveness and minimal side effects, positioning them as a promising new therapeutic option for hyperuricemia- induced renal damage.

Protective Effects of Dioscin and Diosgenin on Plateau Hyperuricemia by Attenuating Renal Inflammation via EPHX2.

Plateau hyperuricemia is a common disease in the plateau area, and the incidence is much higher than that in the plain area. Dioscin (DIO) and its active metabolite Diosgenin (DG) exert therapeutic effects on hyperuricemia through oxidative stress and inflammation. In this study, DIO and its active metabolite DG were taken as the research objects to explore their therapeutic effects on high-altitude hyperuricemia in rats. To evaluate the therapeutic effect of DIO on the rat model of high-altitude hyperuricemia, the evaluation indexes include blood biochemical indexes, renal histopathology, oil red O staining of the kidney, rat kidney index, and rat renal inflammatory factors. Transcriptomics was used to analyze the control group, model group, and drug-administered group to preliminarily explore the protective mechanism of DIO in rats with high-altitude hyperuricemia. An HK-2 high-altitude hyperuricemia cell injury model was established to verify the therapeutic mechanism of DIO in rats with high-altitude hyperuricemia. Western blot was used to detect the expression of related proteins in renal tissues and cell models. The results showed that DIO and its active metabolite DG regulate renal lipid metabolism through the EPHX2 gene, attenuate renal inflammatory reaction, and then promote the excretion of uric acid and reduce its reabsorption, which ultimately achieves the effect of treating plateau hyperuricemia.

Weizmannia coagulans BC99 alleviates hyperuricemia and oxidative stress via DAF-16/SKN-1 activation in Caenorhabditis elegan.

Hyperuricemia (HUA) refers to the presence of excess uric acid (UA) in the blood, which increases the risk of chronic kidney disease and gout. Probiotics have the potential to alleviate HUA. This study established a hyperuricemia model using Caenorhabditis elegans (C. elegans), and studied the anti-hyperuricemia activity and potential mechanisms of Weizmannella coagulans BC99 (W. coagulans) at different concentrations (107 CFU/mL BC99, 108 CFU/mL BC99). Subsequently, we utilized UPLC-Q-TOF/MS to investigate the impact of BC99 on endogenous metabolites in C. elegans and identified pathways and biomarkers through differential metabolomics analysis. The results of this study showed that BC99 treatment significantly reduced the expression of P151.2 and T22F3.3 (p < 0.05), reduced the levels of UA and xanthine oxidase (XOD) in nematodes (p < 0.05), while extending their lifespan and movement ability (p < 0.05). Mechanistically, BC99 activates the transcription factors DAF-16 and SKN-1, thereby inducing the expression of stress response genes, enhancing the activity of antioxidant enzymes and tolerance to heat stress in the body, and reducing the production of ROS (p < 0.001). This effect was most significant in the H-BC99 group. Furthermore, non-targeted metabolomics indicated that BC99 predominantly regulated pathways associated with amino acid metabolism (Carnosine), glycerophospholipid metabolism, and purine metabolism. These results underscore BC99 as an effective and economical adjunct therapeutic agent for hyperuricemia, providing a scientific basis for further development and application.

Microneedle Electrode Patch Modified with Graphene Oxide and Carbon Nanotubes for Continuous Uric Acid Monitoring and Diet Management in Hyperuricemia.

Hyperuricemia is a common disorder induced by purine metabolic abnormality, which will further cause chronic kidney disease, cardiovascular disease, and gout. Its main pathological characteristic is the high uric acid (UA) level in the blood, so that the detection of UA is highly important for hyperuricemia diagnosis and therapy. Herein, we report a biocompatible and minimally invasive microneedle electrode patch (MEP) for continuous UA monitoring and diet management in hyperuricemia. The composite of graphene oxide and carboxylated multiwalled carbon nanotubes was modified on the microneedle electrode surface to enhance its sensitivity, selectivity, and stability, thus realizing the continuous detection of UA in the interstitial fluid to accurately predict the UA level in the blood. This further allowed us to study the hypouricemic effect of anthocyanins on the hyperuricemia model mouse. It was found that anthocyanins extracted from blueberry can effectively inhibit the activity of xanthine oxidase to reduce the production of UA. The UA level of hyperuricemia model mice fed with anthocyanins is ∼1.7 fold lower than that of the control group. We believe that this MEP offers enormous promise for continuous UA monitoring and diet management in hyperuricemia.

Fucoidan Supplementation Relieved Kidney Injury and Modulated Intestinal Homeostasis in Hyperuricemia Mice.

Hyperuricemia is a metabolic disease characterized by an excessively increased level of uric acid (UA) in the blood, with an increasing prevalence and often associated with kidney damage. Gut microbiota and endotoxins of gut origin are key mediators in the gut-kidney axis that can cause renal impairment. The study was to reveal the protective effects of fucoidan on renal injury caused by hyperuricemia. The hyperuricemia model was established in C57BL/6J mice. After 10 weeks of fucoidan supplementation, we found that the levels of serum UA and creatinine were reduced, and the levels of renal tumor necrosis factor α, interleukin-18 (IL-18), IL-6, and interleukin-1β (IL-1β) were also decreased. Fucoidan inhibited the expressions of phosphorylated NF-κB p65, NLRP3, and activated caspase-1 in the kidneys. Fucoidan also regulated the expressions of Bcl-2 family proteins and decreased the activation of caspase-3, thereby exerting antiapoptotic effect. In addition, fucoidan could reduce the expressions of glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1) proteins, thereby promoting the excretion of UA from the kidneys. Moreover, the protective effect of fucoidan on renal injury may be related to maintaining intestinal homeostasis. Fucoidan reduced serum lipopolysaccharide and improved the intestinal mucosal barrier function. Fucoidan decreased the abundances of Blautia, Muribaculaceae, and Dubosiella, and increased the abundances of Lactobacillus. High-dose fucoidan supplementation increased the content of butyric acid and enhanced the expression of ATP binding box transporter G2 (ABCG2) via the AMPK/AKT/CREB pathway in ileum. Conclusion: Fucoidan could protect against hyperuricemia-induced renal injury by inhibiting renal inflammation and apoptosis and modulating intestinal homeostasis in hyperuricemia mice.

Causal effects of gut microbiota on gout and hyperuricemia: insights from genome-wide Mendelian randomization, RNA-sequencing, 16S rRNA sequencing, and metabolomes.

This study investigated the causal relationship between gut microbiota (GM), serum metabolome, and host transcriptome in the development of gout and hyperuricemia (HUA) using genome-wide association studies (GWAS) data and HUA mouse model experiments. Mendelian randomization (MR) analysis of GWAS summary statistics was performed using an inverse variance weighted (IVW) approach to determine or predict the causal role of the GM on gout. The HUA mouse model was used to characterize changes in the gut microbiome, host metabolome, and host kidney transcriptome by integrating cecal 16S rRNA sequencing, untargeted serum metabolomics, and host mRNA sequencing. Our analysis demonstrated causal effects of seven GM taxa on gout, including genera of Ruminococcus, Odoribacter, and Bacteroides. Thirty eight immune cell traits were associated with gout. Dysbiosis of Dubosiella, Lactobacillus, Bacteroides, Alloprevotella, and Lachnospiraceae_NK4A136_group genera were associated with changes in the serum metabolites and kidney transcriptome of the HUA model mice. The changes in the gut microbiome of the HUA model mice correlated significantly with alterations in the levels of serum metabolites such as taurodeoxycholic acid, phenylacetylglycine, vanylglycol, methyl hexadecanoic acid, carnosol, 6-aminopenicillanic acid, sphinganine, p-hydroxyphenylacetic acid, pyridoxamine, and de-o-methylsterigmatocystin, and expression of kidney genes such as CNDP2, SELENOP, TTR, CAR3, SLC12A3, SCD1, PIGR, CD74, MFSD4B5, and NAPSA. Our study demonstrated a causal relationship between GM, immune cells, and gout. HUA development involved alterations in the vitamin B6 metabolism because of GM dysbiosis that resulted in altered pyridoxamine and pyridoxal levels, dysregulated sphingolipid metabolism, and excessive inflammation.

Protective effect of xylosma congesta extract on renal injury in hyperuricemic rats

BackgroundThe purpose of this study was to investigate the protective effect of xylosma congesta extract on kidney injury in hyperuricemic rats. MethodsThe rats were fed yeast extract and intraperitoneal injections of potassium oxonate for 3 weeks to establish the hyperuricemia model. And then the rats were treated with allopurinol and different doses of oak extract. The contents of uric acid in urine and serum, creatinine, and urea nitrogen in serum were detected by biochemical methods. TUNEL was used to detect cell apoptosis in renal tissue. The protein expression of TLR4 and NF- kappa B (NF-κB) p65 and the proportion of CD68 and CD206 positive cells in renal tissue were detected by pathological method. ResultsThe xylosma congesta group showed decreased renal tubular dilatation, decreased renal interstitial inflammatory cell infiltration, decreased serum creatinine content, and decreased apoptotic cell count as compared to the model group. And positive expression of TLR4 and NF-κB decreased with each dose. Additionally, the xylosma congesta groups showed a significant rise in CD206 and a considerable decrease in CD68. ConclusionThe extract from xylosma congesta has the ability to lower serum uric acid and creatinine levels while also providing protection against kidney damage caused by hyperuricemia.

Functional Food Potential of Chrysanthemum morifolium, Perilla frutescens, and Sophora japonica in Managing Hyperuricemia through Dual Enzyme Inhibition.

Amid growing concerns regarding gout and hyperuricemia associated with high-protein and purine-rich diets, the need for effective prevention and management strategies with minimal side effects has become increasingly critical. This study evaluates the potential of three commonly consumed plant-based functional foods, Chrysanthemum morifolium, Perilla frutescens, and Sophora japonica, inhibiting xanthine oxidase (XO) and adenosine deaminase (ADA), key enzymes in uric acid metabolism. Results from hyperuricemia model mice indicate that this blend significantly reduces serum uric acid levels, mirroring the efficacy of conventional prevention and management strategies such as allopurinol but with fewer adverse effects. Liquid chromatography-mass spectrometry (LC-MS) analysis confirms that flavonoids are the primary bioactive agents, exhibiting a strong affinity for XO. These findings highlight the viability of integrating plant-based functional foods into comprehensive gout management strategies, underscoring their role in enhancing patient health through dietary innovation.

Uric acid mediates kidney tubular inflammation through the LDHA/ROS/NLRP3 pathway

ABSTRACT Purpose Hyperuricemia (HUA) is an important factor leading to chronic kidney disease (CKD). The kidney tubular inflammatory response is activated in HUA. This study aimed to investigate whether lactate dehydrogenase A (LDHA) is involved in mediating uric acid-induced kidney tubular inflammatory response. Methods In vivo, an HUA mouse model was established by continuous intraperitoneal injection of potassium oxonate (PO) for one week. A total of 18 C57BL/6J male adult mice were divided into three groups: control group, HUA group, and HUA+oxamate group, with six mice in each group. Oxamate was intraperitoneally injected into the mice one hour after PO injection. In vitro, an HUA model was simulated by stimulating HK-2 cells with uric acid. Oxamate and tempol inhibited LDHA and reactive oxygen species (ROS) in HK-2 cells. Results In HUA mice, blood uric acid levels were significantly elevated. LDHA in kidney tubular cells was significantly increased in both in vivo and in vitro HUA models, accompanied by an increase in kidney tubular inflammation and ROS. Mechanistically, LDHA mediates uric acid-induced inflammation to kidney tubular cells through the ROS/NLRP3 pathway. Pharmacologic inhibition of LDHA or ROS in kidney tubular cells can significantly ameliorate inflammation response caused by uric acid. Conclusions LDHA in kidney tubular cells significantly was increased in HUA models. LDHA mediates kidney inflammation response induced by uric acid through the ROS/NLRP3 pathway. This study may provide a new intervention target for preventing kidney tubular inflammation caused by uric acid.

Structural characterization and anti-hyperuricemic effect of a mannogalactan from Armillariella tabescens mycelium

Hyperuricemia and its complications caused by purine metabolism disorder continue to occur, which require effective drug treatment with fewer side effects. This study explored the positive effects of a natural homogeneous polysaccharide (AT-W) from the mycelium of Armillariella tabescens in a mouse hyperuricemia model. Structural characterization showed that the average molecular weight of AT-W is 25.6 kDa, and it is composed of mannose, galactose, arabinose, and fucose, with molar percentages of 11.46:70.9:4.96:12.67. The main backbone of AT-W is composed of partially 3-O-methylated →6)-α-Galp-(1→, and the branches are mainly composed of α-Manp-(1→, →3)-α-Fucp-(1→. In vivo bioactivity evaluation showed AT-W could not only reduce serum uric acid levels by inhibiting the activity of xanthine oxidase, upregulating the expression of ABCG2 and OAT1, and downregulating the expression of URAT1 but also have a significant protective effect on renal damage caused by hyperuricemia. These findings indicate that AT-W has therapeutic potential for hyperuricemia diseases.

Deletion of the Uox gene generates a mouse model of hyperuricemia with cardiovascular complications

Abstract Background/introductions: Hyperuricemia is associated with hypertension, coronary atherosclerosis and heart failure. However, the causal relationship between uric acid (UA) and cardiovascular disease remains controversial. There has been lack of mouse model for spontaneous hyperuricemia with cardiovascular complications. Purpose We aimed to develop urate oxidase (Uox) deficient mice with hyperuricemia that can survive to adulthood. Methods Uox-knockout mouse model was generated on C57BL/6J background by deleting exon 2-4 of Uox using the CRISPR/Cas9 system. we evaluated the hyperuricemic phenotypes regarding magnitude of serum UA elevation, cardiometabolic abnormalities, and cardiovascular complications. Results The birth rate of homozygous Uox-knockout (Uox -/-) mice was 21.4%. The prototypic Uox -/-mice had 5.5-fold increased serum uric acid (1351.04±276.58 μmol/L) as compared to the wild type mice (P&amp;lt;0.0001)), but mostly died by four weeks. After allopurinol (3ug/g) intervention, they all survived more than eight weeks (median: 12.6 weeks, range:9.6 to 16.0 weeks). The serum UA was 612.55±146.98μmol/L (2.5 times higher than that in WT mice, P&amp;lt;0.0001) in the eight-week-old allopurinol-rescued Uox -/-mice, which also manifested multiple complications including hypertension (systolic blood pressure:155.25±9.48mmHg vs. 109.53±11.02mmHg, P&amp;lt;0.0001), left ventricular remodeling and systolic dysfunction (all echocardiographic functional parameters, P&amp;lt;0.001), aortic endothelial cell impairment (P&amp;lt;0.001 for proliferating cell nuclear antigen and ZO-1, P=0.027 for VE-cadherin), hepatic steatosis and elevated liver enzymes (all enzymes P&amp;lt;0.0001), as well as urate nephropathy, hyperglycemia (P=0.0146 for fasting glucose) and hypercholesteremia (P=0.0045 for total cholesterol). Conclusion The present Uox-/- mice developed spontaneous hyperuricemia complicated with cardiovascular disease and cardiometabolic disorders. This allopurinol-rescued Uox-/- mouse model could survive to adulthood, and may provide a novel tool to study urate biology and hyperuricemia associated early-onset disorders in human. Figure 1 Figure 2

The alleviating effects and mechanisms of Lactiplantibacillus plantarum MC14 on hyperuricemia in mice

Hyperuricemia (HUA) is a chronic disorder resulting from purine metabolic dysregulation. This research explored the alleviating effects and potential mechanisms of Lactiplantibacillus plantarum MC14 on HUA in a mouse model. Further, it investigated the impact of MC14 intervention on the intestinal flora and metabolites of HUA model mice. Results indicated that the activity of MC14 in alleviating HUA may be linked to its abilities to lower serum levels of uric acid, creatinine, and blood urea nitrogen, reduce inflammation, alleviate renal tissue damage, enhance uric acid excretion, inhibit the overactivation of the PI3K/AKT/mTOR signaling pathway, suppress hepatic adenosine deaminase and xanthine oxidase activities, competitively absorb nucleosides and nucleobases, and regulate the intestinal flora. Our research demonstrates that MC14 is a potential candidate for developing novel therapeutics for hyperuricemia.

Study on risk factor analysis and model prediction of hyperuricemia in different populations.

The purpose of the present study was to explore the influencing factors of hyperuricemia (HUA) in different populations in Shandong Province based on clinical biochemical indicators. A prediction model for HUA was constructed to aid in the early prevention and screening of HUA. In total, 705 cases were collected from five hospitals, and the risk factors were analyzed by Pearson correlation analysis, binary logistic regression, and receiver operating characteristic (ROC) curve in the gender and age groups. All data were divided into a training set and test set (7:3). The training set included age, gender, total protein (TP), low-density lipoprotein cholesterol (LDL-C), and 15 other indicators. The random forest (RF) and support vector machine (SVM) methods were used to build the HUA model, and model performances were evaluated through 10-fold cross-validation to select the optimal method. Finally, features were extracted, and the ROC curve of the test set was generated. TP, LDL-C, and glucose (GLU) were risk factors for HUA, and the area under the curve (AUC) value of the SVM validation set was 0.875. The SVM model based on clinical biochemical indicators has good predictive ability for HUA, thus providing a reference for the diagnosis of HUA and the development of an HUA prediction model.

Progress in modeling avian hyperuricemia and gout (Review).

Human organ tissue is vulnerable to hyperuricemia (HUA), which negatively impacts quality of life, particularly when it progresses to gout. Chicken uric acid formation and metabolism are similar to human uric acid metabolism; therefore, theoretically, the genesis and progression of human HUA and gout may be similar to those of poultry models. The present review explored HUA and gout and the progress of poultry-induced HUA and gout models. The present study reviewed procedures of modelling chicken gout and HUA and the detection indices and current concerns regarding these models. Notably, In the production of poultry hyperuricemia model, the combined method of water and food induction has a higher success rate and stability. Compared with mice induced HUA and gout models, poultry induced HUA and gout models had less kidney damage, and the models were stable and long-lasting.

Effect and Mechanism of Uric Acid in Regulating Larval Growth and Development of Drosophila Melanogaster

Objective To explore the effect and mechanism of uric acid (UA) in regulating the larval growth and development of Drosophila melanogaster. Methods A total of 1350 newly hatched first-instar larvae of wild-type Drosophila melanogaster (W1118) were collected,and the Drosophila melanogaster model of hyperuricemia was constructed with a high purine diet.The larvae were assigned into three groups (n=150):control (standard corn meal medium),low-dose adenine (corn meal medium containing 0.05% adenine),and high-dose adenine (corn meal medium containing 0.10% adenine),and two parallel groups were set up.The growth and development of larvae in each group was observed,and the UA and hormone levels were measured.In addition,the expression levels of genes involved in growth and development were determined. Results Compared with the control group,the low- and high-dose adenine groups showed elevated UA levels (both P<0.001) and prolonged developmental period (P=0.024,P<0.001).The high-dose adenine group showed decreased survival rate,pupation rate,and eclosion rate and elevated levels of juvenile hormone (JH) and 20-hydroxyecdysone (20E) (all P<0.001).The PCR results showed that compared with the control group,high-dose adenine upregulated the mRNA levels of reactive oxygen species (ROS),forkhead box O (FOXO),and mammalian target of rapamycin (mTOR) while downregulating the mRNA levels of Sestrin,mTOR complex 1(mTORC1),and AMP-activated protein kinase (all P<0.001). Conclusion High concentrations of UA may promote the expression of ROS/FOXO/mTORC1/mTOR signaling pathway by regulating the levels of JH and 20E,thereby inhibiting the larval growth and development of Drosophila melanogaster.

Empowering probiotics with high xanthine transport for effective hyperuricemia management

ABSTRACT Hyperuricemia, a prevalent metabolic disorder, poses a susceptibility to various complications. The conventional pharmacotherapeutic approaches for hyperuricemia often entail notable adverse effects, posing substantial clinical challenges. Hence, the imperative lies in the development of novel, safe and effective strategies for preventing and treating hyperuricemia. Here, we developed a probiotic Escherichia coli Nissle 1917 strain, designated as YES301, which contains a rationally designed xanthine importer XanQ, enabling efficient uptake of xanthine and hypoxanthine, consequently leading to reduced serum uric acid concentrations and amelioration of renal impairments in a murine model of hyperuricemia. Importantly, YES301 exhibited a therapeutic efficacy comparable to allopurinol, a conventional uric acid-lowering agent, and manifesting fewer adverse effects and enhanced biosafety. These findings highlight the promising potential of engineered probiotics in the management of hyperuricemia through reducing intestinal purine levels.

L-Arginine Potentiates Lisinopril Effects in a Model of Resistant Hyperuricemia and Hypertension in Rats through Decreasing Oxidant Stress and Downregulating Renal ACE Expression

L-Arginine Potentiates Lisinopril Effects in a Model of Resistant Hyperuricemia and Hypertension in Rats through Decreasing Oxidant Stress and Downregulating Renal ACE Expression

Mechanism of Biqi capsules in the treatment of gout based on network pharmacology and experimental verification

Ethnopharmacological relevanceGout is a crystal-related arthropathy caused by monosodium urate (MSU) deposition, resulting from purine metabolism disorders and hyperuricemia (HUA). Gout belongs to the traditional medicine category of Bi syndrome. Biqi capsules (BQ) is a traditional Chinese medicine formula used to treat Bi syndrome. The BQ prescription is derived from the ancient prescription of Hua Tuo, a famous physician in the Han Dynasty. Aim of the studyTo study the effect and mechanism of BQ in treating acute gouty arthritis (AGA) and HUA. Materials and methodsAnalyzing BQ's signaling pathways for gout treatment via network pharmacology. The HUA model was induced orally with adenine and potassium oxonate. The rat AGA model was established by MSU injection. In vitro, MH7A and RAW 246.7 cells were treated with LPS and MSU. Serum uric acid, creatinine, and urea nitrogen levels were evaluated. Kidney and ankle joint pathology was observed via HE staining. Inflammatory signaling pathway proteins, epithelial-mesenchymal transition (EMT) pathway proteins, and uric acid metabolism-related proteins were detected by Western blot. Results1780 potential targets for gout treatment were identified, and 1039 target proteins corresponding to BQ's active ingredients were obtained. Pathway enrichment analysis revealed BQ improved gout mainly through inflammatory pathways. Experimental results showed BQ could reduce serum uric acid level and increase uric acid clearance rate by regulating the expression of adenosine deaminase (ADA), and organic anion transporter 1 (OAT1) and glucose transporter 9 (GLUT9) in HUA mice. BQ could improve renal function and injury by inhibiting the NLRP3 pathway in HUA mice' kidneys. Additionally, BQ could alleviate ankle joint swelling and synovial injury, inhibit the TLR4/NLRP3 pathway, and reduce levels of inflammatory factors including interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor-alpha (TNF-α) in AGA rats. The main component of BQ, brucine, could inhibit the activation of NLRP3/NF-κB pathway induced by MSU and reduce the expression level of inflammatory factors (IL-6, IL-1β, and TNF-α) in macrophages. Brucine could inhibit the activation of the EMT pathway and reduce the expression level of inflammatory factors (IL-6, TNF-α) in human fibroblast-like synoviocytes (MH7A cells) induced by MSU. ConclusionsBQ effectively reduced serum uric acid levels, improved kidney and joint damage, and ameliorated the inflammatory response caused by MSU. Its main component, brucine, effectively improved the inflammatory response and reduced the invasive ability of synoviocytes induced by MSU.