High Purine Diet Research Articles

Phytochemical component profiling and anti-renal fibrosis effects of crude and salt-stir fried Eucommiae Cortex extracts on renal fibrosis rats caused by high-purine diet

A prolonged diet laden with purine-rich foods represents a significant contributor to renal fibrosis (RF). Eucommia ulmoides Oliver, a plant homologous to food and medicinal materials, has long been employed to recover kidney function. This investigation presents a strategy integrating chemistry, biochemistry, and metabolomics to evaluate bioactive components and efficiency mechanism of crude and salt-stir fried Eucommiae Cortex (EC) extracts against RF. Firstly, 155 chemical components were identified in the EC extracts and the contents of 19 and 27 compounds decreased and increased respectively after salt-stir frying. Secondly, various biochemical indicators displayed that salt-stir fried EC (SEC) extracts had the optimal anti-RF effects in adenine-induced RF model rats, which were associated with the attenuation of TGF-β signaling pathway. Finally, untargeted metabolomics analysis demonstrated that after treatments with EC and SEC extracts, 30 and 32 efficacy biomarkers were significantly restored in the RF + EC and RF + SEC groups respectively, involving five metabolic pathways.

The Impact of Uric Acid-Lowering Therapy on the Progression of Non-dialysis Chronic Kidney Disease: A Prospective Cohort Study.

Background Hyperuricemia treatment can positively influence the progression of chronic kidney disease (CKD). This study aimed to evaluate the impact of uric acid-lowering therapy on the progression of CKD after three months. Materials and methods A prospective cohort study was conducted on 126 patients with non-dialysis CKD in Can Tho Central General Hospital, Vietnam, from December 2018 to December 2019. Adopting a questionnaire survey method to collect information, including demographic characteristics, body mass index (BMI), personal history, previous medical history, diet, and use of drugs with the potential to affect the uric acid levels in the blood. Participants also underwent necessary tests, such as serum uric acid, serum creatinine, and blood lipids. Data were analyzed using SPSS software version 26.0(IBM Corp., Armonk, NY). Results The prevalence of hyperuricemia in patients with non-dialysis CKD was 77.8%, and the average serum uric acid was 494.21 ± 131.57 µmol/L. Patients with a high-purine diet were about 18.85 times as likely to have hyperuricemia as those with a low-purine diet (p < 0.001, OR = 18.85, 95%CI: 4.233-83.938). BMI, stages of CKD, and hypertension were associated with the hyperuricemia rate (p < 0.05). After three months of treatment, 46.2% of patients achieved the serum uric acid target, and the patient group combined allopurinol with changing diet had a higher rate than the patient group changing diet only (p = 0.02). There was a moderate inverse correlation between the difference in serum uric acid and the difference in estimated glomerular filtration rate (eGFR) after treatment (r = -0.5, p = 0.001). Conclusions The effective management of hyperuricemia by combining nonpharmacological (changing diet) and/or pharmacological (allopurinol) therapies may meaningfully improve the glomerular filtration rate in non-dialysis CKD patients with hyperuricemia.

Leech Poecilobdella manillensis protein extract ameliorated hyperuricemia by restoring gut microbiota dysregulation and affecting serum metabolites.

Hyperuricemia (HUA) is a public health concern that needs to be solved urgently. The lyophilized powder of Poecilobdella manillensis has been shown to significantly alleviate HUA; however, its underlying metabolic regulation remains unclear. To explore the underlying mechanisms of Poecilobdella manillensis in HUA based on modulation of the gut microbiota and host metabolism. A mouse model of rapid HUA was established using a high-purine diet and potassium oxonate injections. The mice received oral drugs or saline. Additionally, 16S rRNA sequencing and ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry-based untargeted metabolomics were performed to identify changes in the microbiome and host metabolome, respectively. The levels of uric acid transporters and epithelial tight junction proteins in the renal and intestinal tissues were analyzed using an enzyme-linked immunosorbent assay. The protein extract of Poecilobdella manillensis lyophilized powder (49 mg/kg) showed an enhanced anti-trioxypurine ability than that of allopurinol (5 mg/kg) (P < 0.05). A total of nine bacterial genera were identified to be closely related to the anti-trioxypurine activity of Poecilobdella manillensis powder, which included the genera of Prevotella, Delftia, Dialister, Akkermansia, Lactococcus, Escherichia_Shigella, Enterococcus, and Bacteroides. Furthermore, 22 metabolites in the serum were found to be closely related to the anti-trioxypurine activity of Poecilobdella manillensis powder, which correlated to the Kyoto Encyclopedia of Genes and Genomes pathways of cysteine and methionine metabolism, sphingolipid metabolism, galactose metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis. Correlation analysis found that changes in the gut microbiota were significantly related to these metabolites. The proteins in Poecilobdella manillensis powder were effective for HUA. Mechanistically, they are associated with improvements in gut microbiota dysbiosis and the regulation of sphingolipid and galactose metabolism.

Identification of Hyperuricemia Alleviating Peptides from Yellow Tuna Thunnus albacares.

The development of food-derived antihyperuricemic substances is important for alleviating hyperuricemia (HUA) and associated inflammation. Here, novel peptides fromThunnus albacares (TAP) with strong antihyperuricemic activity were prepared. TAP was prepared by alkaline protease (molecular weight <1000 Da), with an IC50 value of xanthine oxidase inhibitory activity of 2.498 mg/mL, and 5 mg/mL TAP could reduce uric acid (UA) by 33.62% in human kidney-2 (HK-2) cells (P < 0.01). Mice were fed a high-purine diet and injected with potassium oxonate to induce HUA. Oral administration of TAP (600 mg/kg/d) reduced serum UA significantly by 42.22% and increased urine UA by 79.02% (P < 0.01) via regulating urate transporters GLUT9, organic anion transporter 1, and ATP-binding cassette subfamily G2. Meantime, TAP exhibited hepatoprotective and nephroprotective effects, according to histological analysis. Besides, HUA mice treated with TAP showed anti-inflammatory activity by decreasing the levels of toll-like receptor 4, nuclear factors-κB p65, NLRP3, ASC, and Caspase-1 in the kidneys (P < 0.01). According to serum non-targeted metabolomics, 91 differential metabolites between the MC and TAP groups were identified, and purine metabolism was considered to be the main pathway for TAP alleviating HUA. In a word, TAP exhibited strong antihyperuricemic activity both in vitro and in vivo.

Unraveling genetic underpinnings of purine content in pork

The significance of purine base content as an important nutrition indicator in foods arises from its potential to trigger hyperuricemia or gout via high-purine diet. Livestock meats, including pork, generally contain moderate to high total purine content (TP). Recent research revealed substantial variations within and across pig breeds, implying genetic factors influencing this trait. Thus, this study aimed to unravel the genetic underpinnings governing purine base content in pork. The heritability estimates (h2) for the four purine traits ranged from 0.14 to 0.35. A total of 14, 36, 19 and 25 quantitative trait loci (QTLs) were identified for guanine, adenine, hypoxanthine, and TP, respectively. Our comprehensive gene set enrichment analysis and gene network analysis revealed 15 promising candidate genes intricately interwoven within diverse purine metabolism pathways, such as purine ribonucleotide metabolic process, purine nucleotide metabolism and transport, and purine salvage pathways, all contributing to TP. Strikingly, most genetic variants significantly associated with TP displayed analogous effects on multiple purine bases. Two distinct and highly significant QTLs (P < 10-12) emerged on Sus Scrofa chromosome (SSC) 12: one impacting guanine content and the other concurrently influencing adenine and hypoxanthine levels. The peak of the guanine QTL on SSC12 resided 1.1 kb downstream of the transmembrane protein 238 like (TMEM238L) gene and is encapsulated within a genomic segment characterized by the histone modification H3K27me3. Focused fine-mapping for the SSC12 QTL associated with adenine and hypoxanthine levels narrowed its scope to around 172 kb, encompassing the growth arrest specific 7 (GAS7) and myosin heavy chain 13 (MYH13) genes. However, the observed QTL effect was not attributed to any missense mutations within the two genes. This pioneering study unveils the genetic variations and candidate genes associated with purine content in livestock, laying a robust foundation for the selective breeding of pig lines with reduced purine base content.

Lacticaseibacillus paracasei JS-3 Isolated from "Jiangshui" Ameliorates Hyperuricemia by Regulating Gut Microbiota and iTS Metabolism.

Background: A diet high in purines can impair the function of the gut microbiota and disrupt purine metabolism, which is closely associated with the onset of hyperuricemia. Dietary regulation and intestinal health maintenance are key approaches for controlling uric acid (UA) levels. Investigating the impacts of fermented foods offers potential dietary interventions for managing hyperuricemia. Methods: In this study, we isolated a strain with potent UA-degrading capabilities from "Jiangshui", a fermented food product from Gansu, China. We performed strain identification and assessed its probiotic potential. Hyperuricemic quails, induced by a high-purine diet, were used to assess the UA degradation capability of strain JS-3 by measuring UA levels in serum and feces. Additionally, the UA degradation pathways were elucidated through analyses of the gut microbiome and fecal metabolomics. Results: JS-3, identified as Lacticaseibacillus paracasei, was capable of eliminating 16.11% of uric acid (UA) within 72 h, rapidly proliferating and producing acid within 12 h, and surviving in the gastrointestinal tract. Using hyperuricemic quail models, we assessed JS-3's UA degradation capacity. Two weeks after the administration of JS-3 (2 × 108 cfu/d per quail), serum uric acid (SUA) levels significantly decreased to normal levels, and renal damage in quails was markedly improved. Concurrently, feces from the JS-3 group demonstrated a significant degradation of UA, achieving up to 49% within 24 h. 16S rRNA sequencing revealed JS-3's role in gut microbiota restoration by augmenting the probiotic community (Bifidobacterium, Bacteroides unclassified_f-Lachnospiraceae, and norank_fynorank_o-Clostridia_UCG-014) and diminishing the pathogenic bacteria (Macrococus and Lactococcus). Corresponding with the rise in short-chain fatty acid (SCFA)-producing bacteria, JS-3 significantly increased SCFA levels (p < 0.05, 0.01). Additionally, JS-3 ameliorated metabolic disturbances in hyperuricemic quails, influencing 26 abnormal metabolites predominantly linked to purine, tryptophan, and bile acid metabolism, thereby enhancing UA degradation and renal protection. Conclusions: For the first time, we isolated and identified an active probiotic strain, JS-3, from the "Jiangshui" in Gansu, used for the treatment of hyperuricemia. It modulates host-microbiome interactions, impacts the metabolome, enhances intestinal UA degradation, reduces levels of SUA and fecal UA, alleviates renal damage, and effectively treats hyperuricemia without causing gastrointestinal damage. In summary, JS-3 can serve as a probiotic with potential therapeutic value for the treatment of hyperuricemia.

Screening of the effective sites of Cichorium glandulosum against hyperuricemia combined with hyperlipidemia and its network pharmacology analysis

Cichorium glandulosum, a common traditional Chinese medicine used by Uyghur and Mongolian ethnic groups, is recognized for its potential to ameliorate metabolic disorders. However, the specific efficacy and mechanisms of Cichorium glandulosum in treating the comorbidity of hyperuricaemia and hyperlipidaemia remain unexplored. This study aims to explore the pharmacological effects and mechanisms of Cichorium glandulosum on this comorbidity through a combination of animal experiments, network pharmacology, and molecular docking techniques. A rat model of hyperuricaemia combined with hyperlipidaemia was established through a high-fat and high-purine diet, and the effective parts of the aqueous extract of Cichorium glandulosum to reduce uric acid and lipid levels were screened and the components of the parts were analysed by LC-MS/MS. The active components, core targets, and key pathways were analysed using network pharmacology and validated by molecular docking. Animal experimental results indicated that the n-butanol extract of Cichorium glandulosum showed a significant therapeutic effect on this comorbidity. Analysis of the n-butanol extract yielded 35 active ingredients and 138 intersecting targets related to diseases. Key targets identified through compound-target-pathway (C-T-P) and Protein-Protein Interaction (PPI) analyses included RELA, CASP3, PTGS2, TNF, and ESR1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed 2515 functional items and 164 pathways, respectively. Molecular docking demonstrated that isochlorogenic acid A, baicalin, chicoric acid, and lactucopicrin showed the highest binding affinity to RELA and PTGS2. The n-butanol fraction from the aqueous extract of Cichorium glandulosum was found to reduce uric acid and lipid levels effectively. In summary, Cichorium glandulosum has a therapeutic effect on hyperuricaemia combined with hyperlipidaemia through its multi-component, multi-target, and multi-pathway characteristics.

Integrated metabolomics and transcriptomics to study mechanisms of Paecilomyces cicadae-fermented Radix astragali in the treatment of hyperuricemia

The prevalence of hyperuricemia (HUA) is rising annually due to societal growth and changes in lifestyle. Bidirectional solid-state fermentation of substrates has demonstrated encouraging uses in the clinical treatment of HUA. To investigate the powerful therapeutic potential of solid-state fermentation products of Radix astragali and Paecilomyces cicadidae (RPF), multi-omics analysis was applied. Spearman analysis between serum biomarkers and differential expressed genes (DEGs) was used to estimate the potential mechanism of RPF against HUA, which was induced by high purine diet (HPD) and potassium oxonate. This study found that the serum uric acid, triglycerides, glucose, and creatinine level were decreased in HUA rats after RPF treatment. In addition, RPF effectively attenuated renal inflammation and lipid accumulation in the livers. Untargeted metabolomics and transcriptome sequencing technology demonstrated that the pathway regulated by RPF were “caffeine metabolism”, “fatty acid biosynthesis”, and “AMPK signaling”. Moreover, the correlation demonstrated that metabolites (allantoin, pyridoxamine, cytidine, cortodoxone, corticostrone) and DEGs (Phald3, Ccdc80) showed significantly positive correlations under RPF influence. Overall, findings of current study indicated the interactions between serum metabolites and renal genes. In line with these findings, the mechanism of the anti-HUA effect of RPF was revealed. In summary, the current study suggest pharmacological support for treating HUA with RPF.

Network pharmacology analysis of the renal protective effects of bracken (Pteridium aquilinum) using experimental data obtained in an avian (quail) hyperuricemia model.

To investigate the nephroprotective potential of orally administered bracken Pteridium aquilinum extract against renal damage in quails, induced by a high-purine diet, to form a foundation for subsequent clinical studies and applications. A mass spectrometry analysis was conducted on the pteridophyte subjected to steam explosion. Network pharmacological methods were then utilized to pinpoint shared targets and pathways, which suggested that Pteridium aquilinum has a capability to counteract renal injury. A total of 48 specific-pathogen-free (SPF) "Difaku" quails were selected and segregated into six distinct groups. The control group received a standard diet, whereas the other groups were fed a high-purine diet. Beginning on day 14, each group was subjected to designated therapeutic measures. The study continued for 40 days, after which relevant biological markers were assessed. Active compound peaks from the steam-exploded Pteridium aquilinum were isolated. Subsequently, 101 targets and several pathways associated with renoprotective effects were discerned, indicating that the Pteridium aquilinum achieves its nephroprotective function through comprehensive regulatory mechanisms. The high-purine diet successfully induced hyperuricemia in the quails, resulting in renal impairment. Following intervention with varied Pteridium aquilinum dosages, renal protective outcomes were evident, though xanthine oxidase activity remained unaffected. Histological analyses demonstrated a notable decrease in renal lesion dimensions post-intervention. The steam-exploded bracken Pteridium aquilinum may provide nephroprotective benefits against hyperuricemia-induced renal damage in quails through comprehensive regulatory processes. This highlights the Pteridium aquilinum's potential as an innovative nephroprotective therapeutic and dietary solution, presenting a promising avenue for hyperuricemia and renal damage treatment and prevention.

Energy insufficiency induced by high purine diet: Catalysts for renal impairment in hyperuricemia nephropathy rat model

A high purine diet emerges as a significant risk factor for hyperuricemia, and this diet may potentiate hyperuricemia nephropathy. Despite this, the mechanistic underpinnings of kidney damage precipitated by a high purine diet warrant further research. In the current investigation, a hyperuricemia nephropathy rat model was developed through induction via a high purine diet. Subsequently, metabolomic and proteomic analyses were employed to explore the metabolic characteristics of the kidney and shed light on the corresponding mechanistic pathway. Finally, fluorescence imaging and 18F-fluorodeoxyglucose positron emission tomography computed tomography (18F-FDG-PET/CT) were utilized to validate the overarching energy metabolism state. The results revealed extensive damage to the kidneys of hyperuricemia nephropathy rats following eight weeks of induction via a high purine diet. We used metabolomic to found that acyl carnitines and L-carnitine reduced in high purine diet group, indicated abnormal fatty acid metabolism. Irregularities were discerned in metabolites and enzymes associated with fatty acid β-oxidation, glycolysis, and oxidative phosphorylation within the kidneys of hyperuricemia nephropathy rats by proteomic and co-expression network analysis. The application of fluorescence imaging and 18F-FDG-PET/CT substantiated the inhibition of fatty acid β-oxidation and glycolysis within the kidneys of hyperuricemia nephropathy rats. On the contrary, a compensatory enhancement in the function of oxidative phosphorylation was observed. Given that the primary energy supply for renal function was derived from the metabolic pathway of fatty acids β-oxidation, any disruption within this pathway could contribute to a deficit in the energy provision to the kidneys. Such an energy insufficiency potentially laid the groundwork for eventual renal impairment. In addition, inhibition of the peroxisome proliferator-activated receptors signaling pathway was noted in the present findings, which could further exacerbate the impediment in the β-oxidation function. In conclusion, it was discerned that a deficiency in energy supply plays a critical role in the kidney injury in hyperuricemia nephropathy rats, thereby endorsing paying more attention to renal energy supply in the therapy of hyperuricemia nephropathy.

Efficient removal of purine compounds from solutions via biomass carbons derived from pomelo peel

The high purine diet could result in the increase of the level of blood uric acid, causing serious health problems such as hyperuricemia, gout, nephropathy and cardiovascular diseases. To find out a safe, cheap and super adsorption material for removing purines in stomach or pretreating high-purine beverages, we used different tissues of pomelo peel to prepare biomass carbon by drying, chemical modification and carbonization and then applied it to remove purine compounds in strong acidic solution, beer and soybean milk. The characteristic analysis of pomelo-peel-derived carbons (PPCs) indicated that the preparation methods significantly affected the structures and adsorption capacities of PPCs. Compared with the biomass carbon derived from bamboo, PPCs exhibited higher adsorption capabilities for purine compounds in strong acidic solution (adsorption rates > 99% in 15min) and soybean milk (adsorption rates > 56% in 30min) but slightly lower adsorption capabilities in beer (adsorption rates > 52% in 30min). In addition, the adsorption capabilities of PPCs for purine compounds in beer and soybean milk were not obviously affected by temperatures. Therefore, PPCs are promising absorbents for applications in removing purine compounds from beverages to produce low-purine, healthier products for treating hyperuricemia. The strong adsorption capabilities of PPCs on purine compounds in strong acidic environment also provides a possibility of using the PPCs as food additives for removing purines in stomach for healthcare applications such as gout prevention after confirming their biosafety.

Paeonia × suffruticosa Andrews leaf extract and its main component apigenin 7-O-glucoside ameliorate hyperuricemia by inhibiting xanthine oxidase activity and regulating renal urate transporters

BackgroundHyperuricemia is an important pathological basis of gout and a distinct hazard factor for metabolic syndromes and cardiovascular and chronic renal disease, but lacks safe and effective treatments currently. Paeonia × suffruticosa Andrews leaf effectively reduced serum uric acid in gout patients; however, the material foundation and the mechanism remain unclear. PurposeTo determine the primary active components and mechanism of P. suffruticosa leaf in hyperuricemic mice. MethodsThe chemical constituents of P. suffruticosa leaf was identified using high-performance liquid chromatographic analysis. The anti-hyperuricemic activity of P. suffruticosa leaf extract (12.5, 25, 50, 100, and 200 mg/kg) and its components was evaluated in hyperuricemic mice induced by a high purine diet for 14 days. Then, the urate-lowering effects of apigenin 7-O-glucoside (0.09, 0.18, and 0.36 mg/kg) were assessed in another hyperuricemic mice model built by administrating potassium oxonate and adenine for 4 weeks. The inhibitory effect of apigenin 7-O-glucoside on uric acid production was elucidated by investigating xanthine oxidase activity in vitro and in serum and the liver and through molecular docking. Immunofluorescence and western blot analyses of the expression of renal urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), organic anion transporters 1 (OAT1), and ATP-binding cassette G member 2 (ABCG2) proteins elucidated how apigenin 7-O-glucoside promoted uric acid excretion. ResultsSix compounds were identified in P. suffruticosa leaf: gallic acid, methyl gallate, oxypaeoniflorin, paeoniflorin, galloylpaeoniflorin, and apigenin 7-O-glucoside. P. suffruticosa leaf extract significantly attenuated increased serum uric acid, creatinine, and xanthine oxidase activity in hyperuricemic mice. Apigenin 7-O-glucoside from P. suffruticosa leaf reduced uric acid, creatinine, and malondialdehyde serum levels, increased superoxide dismutase activity, and partially restored the spleen coefficient in hyperuricemic mice. Apigenin 7-O-glucoside inhibited xanthine oxidase activity in vitro and decreased serum and liver xanthine oxidase activity and liver xanthine oxidase protein expression in hyperuricemic mice. Molecular docking revealed that apigenin 7-O-glucoside bound to xanthine oxidase. Apigenin 7-O-glucoside facilitated uric acid excretion by modulating the renal urate transporters URAT1, GLUT9, OAT1, and ABCG2. Apigenin 7-O-glucoside protected against renal damage and oxidative stress caused by hyperuricemia by reducing serum creatinine, blood urea nitrogen, malondialdehyde, and renal reactive oxygen species levels; increasing serum and renal superoxide dismutase activity; restoring the renal coefficient; and reducing renal pathological injury. ConclusionApigenin 7-O-glucoside is the main urate-lowering active component of P. suffruticosa leaf extract in the hyperuricemic mice. It suppressed liver xanthine oxidase activity to decrease uric acid synthesis and modulated renal urate transporters to stimulate uric acid excretion, alleviating kidney damage caused by hyperuricemia.

Accumulation of Renal Fibrosis in Hyperuricemia Rats Is Attributed to the Recruitment of Mast Cells, Activation of the TGF-β1/Smad2/3 Pathway, and Aggravation of Oxidative Stress

Renal fibrosis is relentlessly progressive and irreversible, and a life-threatening risk. With the continuous intake of a high-purine diet, hyperuricemia has become a health risk factor in addition to hyperglycemia, hypertension, and hyperlipidemia. Hyperuricemia is also an independent risk factor for renal interstitial fibrosis. Numerous studies have reported that increased mast cells (MCs) are closely associated with kidney injury induced by different triggering factors. This study investigated the effect of MCs on renal injury in rats caused by hyperuricemia and the relationship between MCs and renal fibrosis. Our results reveal that hyperuricemia contributes to renal injury, with a significant increase in renal MCs, leading to renal fibrosis, mitochondrial structural disorders, and oxidative stress damage. The administration of the MCs membrane stabilizer, sodium cromoglycate (SCG), decreased the expression of SCF/c-kit, reduced the expression of α-SMA, MMP2, and inhibited the TGF-β1/Smad2/3 pathway, thereby alleviating renal fibrosis. Additionally, SCG reduced renal oxidative stress and mitigated mitochondrial structural damage by inhibiting Ang II production and increasing renal GSH, GSH-Px, and GR levels. Collectively, the recruitment of MCs, activation of the TGF-β1/Smad2/3 pathway, and Ang II production drive renal oxidative stress, ultimately promoting the progression of renal fibrosis in hyperuricemic rats.

Effects of a Macroporous Resin Extract of Dendrobium officinale Leaves in Rats with Hyperuricemia Induced by Anthropomorphic Unhealthy Lifestyle.

Hyperuricemia (HUA) has received increased attention in the last few decades due to its global prevalence. Our previous study found that administration of a macroporous resin extract of Dendrobium officinale leaves (DoMRE) to rats with HUA that was induced by exposure to potassium oxazine combined with fructose and a high-purine diet led to a significant reduction in serum uric acid (SUA) levels. The aim of this study was to explore the effects of DoMRE on hyperuricemia induced by anthropomorphic unhealthy lifestyle and to elucidate its possible mechanisms of action. Dosages (5.0 and 10.0 g/kg/day) of DoMRE were administered to rats daily after induction of HUA by anthropomorphic unhealthy lifestyle for 12 weeks. The levels of UA in the serum, urine, and feces; the levels of creatinine (Cr) in the serum and urine; and the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum were all measured using an automatic biochemical analyzer. The activities of xanthine oxidase (XOD) and adenosine deaminase (ADA) in the serum, liver, and intestine tissue supernatant were measured using appropriate kits for each biological target. The expressions levels of UA transporters (ABCG2 and GLUT9), tight junction (TJ) proteins (ZO-1 and occludin), and inflammatory factors (IL-6, IL-8, and TNF-α) in the intestine were assayed by immunohistochemical (IHC) staining. Hematoxylin and eosin (H&E) staining was used to assess histological changes in the renal and intestinal tissues. DoMRE treatment significantly reduced SUA levels and concomitantly increased fecal UA (FUA) levels and the fractional excretion of UA (FEUA) in HUA rats. Furthermore, DoMRE significantly reduced both the XOD activity in the serum, liver, and intestine and the ADA activity in the liver and intestine. DoMRE also effectively regulated the expression of GLUT9 and ABCG2 in the intestine, and it significantly upregulated the expression of the intestinal TJ proteins ZO-1 and occludin. Therefore, DoMRE reduced the damage to the intestinal barrier function caused by the increased production of inflammatory factors due to HUA to ensure normal intestinal UA excretion. DoMRE demonstrated anti-HUA effects in the HUA rat model induced by an anthropomorphic unhealthy lifestyle, and the molecular mechanism appeared to involve the regulation of urate transport-related transporters (ABCG2 and GLUT9) in the intestine, protection of the intestinal barrier function to promote UA excretion, and inhibition of XOD and ADA activity in the liver and intestine to inhibit UA production in the HUA-induced rats.

Rutin ameliorates gout via reducing XOD activity, inhibiting ROS production and NLRP3 inflammasome activation in quail

Gout is a metabolic disease affected by monosodium urate (MSU) deposition, which is directly related to hyperuricemia. Recent reports on the prevalence and incidence of gout have been widely circulated worldwide. Currently, the anti-gout drugs in clinical practice are mainly small-molecule synthetic drugs, and the effectiveness and safety are limited. Reducing uric acid and inhibiting inflammation are the focused areas of drug research and development on gout. Rutin, a natural flavonoid, has been reported to alleviate inflammation in various diseases. However, whether rutin exerts protective effects on gout remains to be elucidated. This study used quails without urate oxidase as experimental animals to induce endogenous gout models through a high purine diet. We confirmed that quail in the model group developed gout symptoms at 30 days of the experiment. And the targets of uric acid metabolism, oxidative stress level, and NLRP3 inflammasome were dysregulated in quails. Rutin treatment improves gout and reduces inflammatory expression in quail. We further confirmed that rutin treatment reduced XOD activity and uric acid levels in quail. And rutin inhibited ROS production, restored oxidative stress balance, inhibited NLRP3 inflammasome activation, and exerted anti-inflammatory effects. We extracted and identified the fibroblast-like synoviocytes (FLS) for the first time. The results showed that rutin could reduce ROS production and NLRP3 inflammasome activation of FLS after uric acid stimulation. In conclusion, our findings underscore that rutin may be a gout protective agent by reducing XOD activity, inhibiting ROS production and NLRP3 inflammasome activation. Meanwhile, this study also provides an available animal model for the research drugs of gout.

Probiotic effects of Lacticaseibacillus rhamnosus 1155 and Limosilactobacillus fermentum 2644 on hyperuricemic rats.

Hyperuricemia is the main cause of gout and involved in the occurrence of multiple diseases, such as hypertension, metabolic disorders and chronic kidney disease. Emerging evidence suggests that lactic acid bacteria (LAB) have shown the beneficial effects on the prevention or treatment of hyperuricemia. In this study, the urate-lowering effect of two LAB strains, Lacticaseibacillus rhamnosus 1155 (LR1155) and Limosilactobacillus fermentum 2644 (LF2644) on hyperuricemic rats were investigated. A hyperuricemic rat model was induced by the intragastric treatment of potassium oxonate, combined with a high purine diet. The oral administration of LR1155, LF2644, or a combination of LR1155 and LF2644 for 4 weeks significantly prevented the rise of the serum uric acid (UA) induced by hyperuricemia. LR1155 and LF2644 significantly elevated the fecal UA levels, increased the UA content and up-regulated gene expression of UA transporter, ATP-binding cassette subfamily G-2 (ABCG2), in colon and jejunum tissues, suggesting the accelerated UA excretion from the intestine. Besides, LR1155 significantly inhibited the activity of xanthine oxidase (XOD) in liver and serum, benefited the reduce of UA production. In addition, LF2644 strengthened the gut barrier functions through an up-regulation of the gene expressions for occluding and mucin2, accompanied with the reduced inflammatory indicators of lipopolysaccharide (LPS) and interleukin-1β (IL-1β) in hyperuricemic rat. Moreover, using 16s rDNA high-throughput sequencing of feces, LR1155 was shown to improve the hyperuricemia induced gut microbial dysbiosis. The genera Roseburia, Butyricicoccus, Prevotella, Oscillibacter, and Bifidobacterium may associate with the effect of LR1155 on microbiota in hyperuricemic rats. Collectively, the results indicated that LR1155 and LF2644 exhibit urate-lowering effects and could be used alone or in combination as a new adjuvant treatment for hyperuricemia.

Folic acid and zinc improve hyperuricemia by altering the gut microbiota of rats with high-purine diet-induced hyperuricemia.

A high-purine diet can cause hyperuricemia and destroy the microbial composition of the gut microbiota. Both folic acid and zinc significantly reduce uric acid levels and alleviate hyperuricemia. However, whether the underlying mechanisms are associated with the regulation of the gut microbiota remain unknown. To explore alterations of the gut microbiota related to folic acid and zinc treatment in rats with hyperuricemia in our study. A hyperuricemic rat model was established with a high-purine diet. The effects of folic acid and zinc on uric acid levels were evaluated. Alterations of the gut microbiota related to hyperuricemia and the treatments were evaluated by sequencing using the Illumina MiSeq system. The results demonstrated that uric acid levels dropped observably, and the activities of adenosine deaminase (ADA) and xanthine oxidase (XOD) were downregulated after folic acid or zinc intervention. 16S rRNA gene sequencing-based gut microbiota analysis revealed that folic acid and zinc enhanced the abundance of probiotic bacteria and reduced that of pathogenic bacteria, thus improving intestinal barrier function. PICRUST analysis indicated that folic acid and zinc restored gut microbiota metabolism. These findings indicate that folic acid and zinc ameliorate hyperuricemia by inhibiting uric acid biosynthesis and stimulating uric acid excretion by modulating the gut microbiota. Thus, folic acid and zinc may be new and safe therapeutic agents to improve hyperuricemia.

Prehyperuricemia: New Milestone in Metabolic Disorders

The global population is living amid a metabolic explosion. The prevalence of hyperuricemia, as a metabolic disorder and a causal agent of non-communicable diseases, has been gearing up rapidly worldwide during the last two decades due to consuming a high purine diet, alcohol, red meat, high fructose-containing food, and lifestyle changes. The invisible bond between hyperuricemia and many non-communicable diseases is more robust than before. During the evolution of hyperuricemia, systemic inflammation develops, leading to endothelial dysfunction and end-organ injury. These molecular changes were not recognized previously. Hyperuricemia is now a metabolic, more clearly a vascular disorder than a crystallization disease. Asymptomatic hyperuricemia is no more benign, and gout is not synonym with hyperuricemia or vice versa. Diagnose hyperuricemia in an early stage at a high normal level and control it to prevent the development and complications of many hyperuricemia-related extra-articular diseases. For more acceptance and importance, this high normal level of serum uric acid can be named prehyperuricemia. As in the case of prediabetes and prehypertension, prehyperuricemia should be diagnosed early irrespective of age and sex; preventive measures have to be taken and maintain uric acid at a safer level. keywords: Serum uric acid, hyperuricemia, prehyperuricemia, high normal value of serum uric acid, metabolic disorder, non-communicable disorder, and molecular mechanism.

Case report and disease’ review: tophaceous gouty arthropathy

Gout is a common inflammatory and metabolic disorder of the joints and probably other organs, especially the kidneys. It has a definitive genetic and environmental background, making it mainly a disease of middle-aged and elderly males, infrequently inflicting postmenopausal and elderly women who usually have arterial hypertension, renal impairment, and usually on diuretics. Excessive tissue urate turnover and persistent hyperuricemia is the hallmark of the disease. A typical algorithm is characterized by acute attack of the monoarticular joint, the metatarsophalangeal joint of the big toe often is involved (podagra), but tarsal joints, ankles, and knees might also be affected. Chronic asymmetric polyarticular arthritis that might be confused with classical Rheumatoid Arthritis might be encountered in some patients and in recurrent and relapsing diseases. In this setting, many organs and tissues are affected by the deposition of monosodium urate (MSU) crystals other than synovium, bursae, tendons, and periarticular tissues. The risk of involvement of renal interstitium or uric acid nephrolithiasis has a particular interest in the course of the disease. By the inflammation and collection of MSU crystals in form of tophi that might involve many tissues and occasionally the pinna of the ears, this kind of tophaceous gout is rarely observed nowadays, especially in our community (Middle East region). The patient who is presented here has exhibited acute attack on the top of chronic tophaceous gouty arthritis. The recent epidemiologic reports revealed that gout has given different results. This wide variation is attributed to the population studied and methods employed, but overall, for the prevalence of &lt;1% to 6.8% and an incidence of 0.58-2.89 per 1,000 person per year. The most noticeable risks for gout are obesity and associated metabolic syndrome (insulin resistance, hypertension, dyslipidaemia), dietary factors, high fructose-containing diet, high purine diet (red meat, internal organ’s meat ,seafood) high consumption of alcohol, and exclusively beer ( as in our patient’s case ), a wide variety of disorders that are characterized by high urate turnover like myeloproliferative disorders, neoplasms, psoriasis, haemolytic anaemias, medications , to under-secretion of urate like renal insufficiency.

Probiotic Characterization of Lactobacillus brevis MJM60390 and In Vivo Assessment of Its Antihyperuricemic Activity.

Uric acid is the final product of purine metabolism in human. The increase of serum uric acid is tightly related to the incidence of hyperuricemia and gout. Also, it has been reported that the intake of purine-rich foods like meat and seafood is associated with an increased risk of gout. Therefore, the reduction of purine absorption is one of therapeutic approaches to prevent hyperuricemia and gout. Currently, probiotics are being studied for the management of hyperuricemia and gout. In this study, we aimed to investigate the effect of Lactobacillus brevis MJM60390 on hyperuricemia induced by a high-purine diet and potassium oxonate in a mouse model. L. brevis MJM60390 among 24 lactic acid bacteria isolated from fermented foods showed the highest ability to assimilate inosine and guanosine in vitro and typical probiotic characteristics, like the absence of bioamine production, D-lactate production, hemolytic activity, as well as tolerance to simulated orogastrointestinal conditions and adherence to Caco-2 cells. In an in vivo animal study, the uric acid level in serum was significantly reduced to a normal level after oral administration of L. brevis MJM60390 for 2 weeks. The activity of xanthine oxidase catalyzing the formation of uric acid was also inhibited by 30%. Interestingly, damage to the glomerulus, Bowman's capsule, and tubules in the hyperuricemia model were reversed by supplementation with this strain. Fecal microbiome analysis revealed that L. brevis MJM60390 supplementation enhanced the relative abundance of the Rikenellaceae family, which produces the short-chain fatty acid butyrate and helps to maintain good gut condition. Therefore, these results demonstrated that L. brevis MJM60390 can be a probiotic candidate to prevent hyperuricemia.