Eggshell Membrane Ameliorates Hyperuricemia by Increasing Urate Excretion in Potassium Oxonate-Injected Rats.

Hyperuricemia is the primary cause of gouty arthritis and other metabolic disorders. Eggshell membrane (EM) is an effective and safe supplement for curing pain and stiffness connected with osteoarthritis. However, the effect of EM on hyperuricemia is unclear. This study determines the effects of EM on potassium oxonate-injected hyperuricemia. Uric acid, creatinine, blood urea nitrogen concentrations in the serum, and xanthine oxidase activity in the liver are measured. Protein levels of renal urate transporter 1 (URAT1), organic anion transporters 1 (OAT1), glucose transporter 9 (GLUT9), and ATP-binding cassette transporter G2 (ABCG2) in the kidney are determined with renal histopathology. The results demonstrate that EM reduces serum uric acid levels and increases urine uric acid levels in hyperuricemic rats. Moreover, EM downregulates renal URAT1 protein expression, upregulates OAT1 and ABCG2, but does not change GLUT9 expression. Additionally, EM does not change xanthine oxidase activity in the liver or the serum. EM also decreases uric acid uptake into oocytes expressing hURAT1. Finally, EM markedly reduces renal inflammation and serum interleukin-1ß levels. These findings suggest that EM exhibits antihyperuricemic effects by promoting renal urate excretion and regulating renal urate transporters. Therefore, EM may be useful in the prevention and treatment of gout and hyperuricemia.

Elevated Urate Levels Do Not Alter Bone Turnover Markers: Randomized Controlled Trial of Inosine Supplementation in Postmenopausal Women.

OBJECTIVE: Observational studies have consistently demonstrated that serum urate level positively correlates with bone mineral density (BMD). We undertook this study to determine whether moderate hyperuricemia induced by inosine supplements influences bone turnover markers in postmenopausal women over a 6-month period. METHODS: One hundred twenty postmenopausal women were recruited for a 6-month randomized, double-blind, placebo-controlled trial. Key exclusion criteria were osteoporosis, previous fragility fracture, bisphosphonate therapy, gout, kidney stones, and a urine pH level of ≤5.0. Participants were randomized in a 1:1 ratio to receive placebo or inosine. The coprimary end points were change in levels of N-propeptide of type I procollagen (PINP) and change in levels of ß-C-telopeptide of type I collagen (ß-CTX). Change in BMD, as measured by dual x-ray absorptiometry, was an exploratory end point. RESULTS: Administration of inosine led to a significant increase in serum urate concentration over the study period (P < 0.0001 for all follow-up time points). At week 26, the mean change in serum urate concentration was +0.13 mmoles/liter (+2.2 mg/dl) in the inosine group and 0.00 mmoles/liter (0 mg/dl) in the placebo group. There was no difference in PINP or ß-CTX levels between groups over the 6 months. There were no significant changes in bone density between groups over the 6 months. Adverse events and serious adverse events were similar between the 2 groups. CONCLUSION: This clinical trial shows that although inosine supplementation leads to sustained increases in serum urate levels over a 6-month period, it does not alter markers of bone turnover in postmenopausal women. These findings do not support the concept that urate has direct biologic effects on bone turnover.

Association of Maternal Hyperuricemia with Post-Spinal Hypotension in Pre-Eclamptic Parturients Undergoing Emergency Cesarean Delivery: a Prospective Observational Study.

Pre-eclampsia is commonly associated with higher serum uric acid levels, which is known to increase vascular tone. A previous retrospective study established a positive correlation between raised serum uric acid levels and reduced incidence of post-spinal hypotension. However, until date, this correlation has not been prospectively evaluated in exclusively pre-eclamptic women. Pre-eclamptic parturients undergoing emergency cesarean delivery under subarachnoid block were included. Sample for measuring serum uric acid level was obtained prior to shifting patients for cesarean delivery. Following spinal anesthesia, we recorded episodes of hypotension (fall of mean arterial pressure more than 20% from baseline values), use of vasopressors, and intraoperative blood loss. Our primary objective was to study the association between maternal hyperuricemia and incidence of post-spinal hypotension. Our secondary objectives included amount of vasopressors administered to maintain targeted mean arterial pressure before delivery of the baby, intraoperative blood loss, and immediate neonatal outcome. A total of 95% parturients had hyperuricemia, with mean serum uric acid level being 6.94 ± 0.9 mg/dl. Incidence of post-spinal hypotension was significantly lower in women who had hyperuricemia as compared with those with normal serum uric acid levels (21% vs 75%; p = 0.015). Mean serum uric acid levels were significantly high (p = 0.001) in patients not requiring any vasopressors (7.2 ± 1.2 mg/dl) than in those requiring moderate (5.70 ± 0.79 mg/dl) to high dose (5.75 ± 0.77 mg/dl) of vasopressors. There is a high incidence of hyperuricemia in pre-eclamptic parturients. In these patients, elevated serum uric acid levels is associated with lower incidence of post-spinal hypotension and reduced need of vasopressors to maintain maternal blood pressure within a normal range.

A 12-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial for Evaluation of the Efficacy and Safety of DKB114 on Reduction of Uric Acid in Serum.

This study sought to investigate the antihyperuricemia efficacy and safety of DKB114 (a mixture of Chrysanthemum indicum Linn flower extract and Cinnamomum cassia extract) to evaluate its potential as a dietary supplement ingredient. This clinical trial was a randomized, 12-week, double-blind, placebo-controlled study. A total of 80 subjects (40 subjects with an intake of DKB114 and 40 subjects with that of placebo) who had asymptomatic hyperuricemia (7.0-9.0 mg/dL with serum uric acid) was randomly assigned. No significant difference between the DKB114 and placebo groups was observed in the amount of uric acid in serum after six weeks of intake. However, after 12 weeks of intake, the uric acid level in serum of subjects in the DKB114 group decreased by 0.58 ± 0.86 mg/dL and was 7.37 ± 0.92 mg/dL, whereas that in the placebo group decreased by 0.02 ± 0.93 mg/dL and was 7.67 ± 0.89 mg/dL, a significant difference (p = 0.0229). In the analysis of C-reactive protein (CRP) change, after 12 weeks of administration, the DKB114 group showed an increase of 0.05 ± 0.27 mg/dL (p = 0.3187), while the placebo group showed an increase of 0.10 ± 0.21 mg/dL (p = 0.0324), a statistically significant difference (p = 0.0443). In the analysis of amount of change in apoprotein B, after 12 weeks of administration, the DKB114 group decreased by 4.75 ± 16.69 mg/dL (p = 0.1175), and the placebo group increased by 3.13 ± 12.64 mg/dL (p = 0.2187), a statistically significant difference between the administration groups (p = 0.0189). In the clinical pathology test, vital signs and weight measurement, and electrocardiogram test conducted for safety evaluation, no clinically significant difference was found between the ingestion groups, confirming the safety of DKB114. Therefore, it may have potential as a treatment for hyperuricemia and gout. We suggest that DKB114 as a beneficial and safe food ingredient for individuals with high serum uric acid. Trial registration (CRIS.NIH. go. Kr): KCT0002840.

Protein energy-wasting associated with nephrotic syndrome - the comparison of metabolic pattern in severe nephrosis to different stages of chronic kidney disease.

BACKGROUND: Nephrotic syndrome (NS) is associated with a hypercatabolic state expressed as an exacerbated degradation of muscle mass. However, the clinical significance of this phenomenon has not yet been investigated. The aim of the study was to evaluate the nutritional status of patients with severe NS (defined as nephrotic range proteinuria with hypoalbuminemia ≤2.5 g/dL) and estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m2 in comparison to patients in different stages of chronic kidney disease (CKD). METHODS: Twenty men with severe NS (NS group) and 40 men without proteinuria similar in term of serum creatinine (control group) were included into the study. A retrospective cohort of 40 men with CKD stage G4 (PreD group) and 20 haemodialysis men (HD group) were added to the analysis after matching for age, height and weight using propensity score matching. The bioimpedance spectroscopy and biochemical nutritional markers were evaluated. RESULTS: Nephrotic patients had a significantly lower lean tissue mass (LTM; p = 0.035) and index (a quotient of LTM over height squared, LTI; p = 0.068), with an expected deficiency of LTM by 3.2 kg, and LTI by 0.9 kg/m2 when compared to the control group. A significant lean tissue deficit (defined as LTI below the lower limit of the reference range by 1.0 kg/m2) was observed in 12.5% of patients in the control group in comparison to 31.7% with advanced CKD (PreD+HD; p = 0.032) and 50% with NS (p = 0.003). NS group presented with higher phosphorus (p = 0.029), uric acid (p = 0.002) and blood urea (p = 0.049) than the control group. Blood urea was strongly negatively correlated with LTM in NS (r = - 0.64, p = 0.002). Nine nephrotic patients (45%) were identified as hypercatabolic based on severe hyperphosphatemia (> 5.0 mg/dL) and/or hyperuricemia (> 8.0 mg/dL), and were characterized by higher blood urea and lower prealbumin, as well as LTM lower by 5.6 kg than in less catabolic individuals. CONCLUSIONS: In term of lean tissue amount, NS group was more similar to advanced CKD than to the control group. We concluded that specific metabolic pattern with elevated phosphorus, uric acid and blood urea, and lean tissue deficiency may be defined as protein-energy wasting associated with nephrotic syndrome (neph-PEW).

Total glucosides of herbaceous peony (Paeonia lactiflora Pall.) flower attenuate adenine- and ethambutol-induced hyperuricaemia in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Herbaceous peony (Paeonia lactiflora Pall.) flower has been used widely in dietotherapy in China and other countries. It has good ethnopharmacological value in the treatment of various metabolic diseases. However, the molecular mechanisms by which it lowers serum uric acid are unknown. The development of pharmaceutical resources is very important. Here, we sought to elucidate the mode of action of herbaceous peony in terms of reducing uric acid levels. AIM OF THE STUDY: In the present research, the effects of the total glucosides of herbaceous peony flower were investigated in a rat hyperuricaemia model. Another aim of the study was to clarify the mechanism by which herbaceous peony flower (TGPF) lowers serum uric acid levels. MATERIALS AND METHODS: A hyperuricaemic rat model was induced via intragastric administration of 100 mg/kg adenine and 250 mg/kg ethambutol hydrochloride (EH) for 23 d. Then TongFengShu 600 mg/kg, allopurinol 42 mg/kg, or TGPF (50 mg/kg, 100 mg/kg, or 200 mg/kg) was administered 1 h after the adenine and EH treatments. RESULTS: TGPF improved weight loss and decreased serum UA, XOD, MCP-1, TNF-α, Cr, and BUN in the rats with hyperuricaemic nephropathy. TGPF downregulated renal URAT1 and GLUT9, upregulated renal OAT1, and ameliorated histopathological changes in the thymus, spleen, and kidney. CONCLUSION: TGPF is promising as a therapeutic agent against hyperuricaemia. It regulates the uric acid transporters and diminished serum uric acid levels, and alleviates renal pathology associated with hyperuricaemia.

Omega-3 Polyunsaturated Fatty Acids Inhibit the Function of Human URAT1, a Renal Urate Re-Absorber.

The beneficial effects of fatty acids (FAs) on human health have attracted widespread interest. However, little is known about the impact of FAs on the handling of urate, the end-product of human purine metabolism, in the body. Increased serum urate levels occur in hyperuricemia, a disease that can lead to gout. In humans, urate filtered by the glomerulus of the kidney is majorly re-absorbed from primary urine into the blood via the urate transporter 1 (URAT1)-mediated pathway. URAT1 inhibition, thus, contributes to decreasing serum urate concentration by increasing net renal urate excretion. Here, we investigated the URAT1-inhibitory effects of 25 FAs that are commonly contained in foods or produced in the body. For this purpose, we conducted an in vitro transport assay using cells transiently expressing URAT1. Our results showed that unsaturated FAs, especially long-chain unsaturated FAs, inhibited URAT1 more strongly than saturated FAs. Among the tested unsaturated FAs, eicosapentaenoic acid, α-linolenic acid, and docosahexaenoic acid exhibited substantial URAT1-inhibitory activities, with half maximal inhibitory concentration values of 6.0, 14.2, and 15.2 µM, respectively. Although further studies are required to investigate whether the ω-3 polyunsaturated FAs can be employed as uricosuric agents, our findings further confirm FAs as nutritionally important substances influencing human health.

The Associations Between Gonadal Hormones and Serum Uric Acid Levels in Men and Postmenopausal Women With Diabetes.

Introduction: In assessing the development of hyperuricemia in diabetic adults, the role of the sex steroid axis is underappreciated. Furthermore, dehydroepiandrosterone (DHEA) has been recommended as a nutritional supplement. However, is DHEA suitable for diabetic adults with hyperuricemia? This issue has received little attention. Aim: The objective of this study was to investigate the associations between gonadal hormones and uric acid (UA) levels in diabetic adults, paying particular attention to the association between DHEA and UA levels. Methods: We analyzed 4,426 participants out of 4,813 diabetic adults enrolled from seven communities in a cross-sectional survey conducted in 2018. Participants underwent several examinations, including assessments of anthropometric parameters, blood pressure, glucose, lipid profiles, UA, total testosterone (TT), estradiol (E2), the follicle-stimulating hormone (FSH), the luteinizing hormone (LH), and dehydroepiandrosterone (DHEA). Results: Among men and compared with individuals in the first quartile, participants in the fourth quartile of TT and FSH had odds of hyperuricemia that were significantly decreased by so much as 48 and 34%, respectively (both P < 0.05). However, participants in the fourth quartile of DHEA had 79% increased odds of hyperuricemia (P < 0.05). Among postmenopausal women, participants in the fourth quartile of DHEA, TT, and LH had odds of hyperuricemia that were significantly increased by 155, 99, and 76%, respectively (all P < 0.05). These associations were adjusted for potential confounding factors. Conclusions: Sex differences were found in the associations between gonadal hormones and UA levels in diabetic men and postmenopausal women, which should be monitored to prevent hyperuricemia when sex hormone treatment, especially DHEA, is administered. Further studies are needed.

Association between dyslipidemia and serum uric acid levels in Korean adults: Korea National Health and Nutrition Examination Survey 2016-2017.

OBJECTIVES: Despite the growing pieces of evidence linking hyperuricemia with metabolic syndrome and cardiovascular disease, the relationship between dyslipidemia and serum uric acid has not yet been established. This study aimed to investigate the association between individual components of dyslipidemia and serum uric acid by using the nationally representative Korea National Health and Nutrition Examination Survey 2016-2017. METHODS: A total of 8,722 participants (age ≥ 19 years) without missing values were analyzed for this study. Serum uric acid levels according to the presence of individual dyslipidemia components were calculated using multivariable-adjusted general linear models (GLM). Odds ratios of individual dyslipidemia components to hyperuricemia were calculated using unadjusted and multivariable-adjusted logistic regression analysis. RESULTS: A total of 1,061 participants were identified as having hyperuricemia, with a prevalence of 12.2%. Multivariable-adjusted GLM demonstrated a significant trend between individual dyslipidemia components and serum uric acid levels (P < 0.05). A positive association between the numbers of dyslipidemia components and the increments of serum uric acid levels was also observed (P < 0.001). In multivariable-adjusted logistic regression analysis, odds ratios (OR) and 95% confidence interval (CI) of all dyslipidemia components to hyperuricemia were shown to be statistically significant (P < 0.05). When further adjusted for the combined components themselves, each 10 mg/dL increments of total cholesterol (OR 1.053; 95% CI 1.028-1.079), triglycerides (OR 1.017; 95% CI 1.009-1.026) and HDL-C (OR 0.804; 95% CI 0.729-0.887), retained significant correlation with hyperuricemia. CONCLUSION: Our study demonstrated that the dyslipidemia components of serum total cholesterol, triglycerides and LDL-C levels are positively associated with serum uric acid levels, whereas serum HDL-C levels are inversely related. Further complementary studies regarding other lipid parameters are needed to confirm the accurate association between dyslipidemia and serum uric acid levels.

Effects of Highly Oxygenated Water in a Hyperuricemia Rat Model.

Recent years have seen a rapidly rising number of oxygenated water brands that claim to impart health benefits and increase athletic performance by improving oxygen availability in the body. Drinks with higher dissolved oxygen concentrations have in recent times gained popularity as potential ergogenic aids, despite the lack of evidence regarding their efficacy. The aim of this study was to characterize oxygenated water and assess the improvement in uric acid metabolism while identifying performance enhancements in animals administered oxygenated water. Oxygenated water was characterized by hydrogen and oxygen nuclear magnetic resonance (NMR) spectroscopy. Hyperuricemia in rats was induced by treatment with oxonic acid potassium salt, and the animals were given oxygenated drinking water before, during, or after oxonic acid treatment. Serum uric acid was measured to confirm the effects on uric acid metabolism. Following oxygenation, the full width at half maximum (FWHM) was reduced to 11.56 Hz and 64.16 Hz in the hydrogen and oxygen NMR spectra, respectively. Oxygenated water molecule clusters were reduced in size due to the reduction in FWHM. Oxygen concentration did not vary significantly with increased temperature. However, standing time played a critical role in the amount of oxygen dissolved in the water. The rat studies indicated that oxygenated water reduced serum uric acid levels and their rate of increase and enhanced uric acid metabolism. A significant improvement in uric acid metabolism and rate of increase in serum uric acid concentration was observed in hyperuricemic rats administered oxygenated water compared to that in rats administered regular water. High oxygen concentrations enhanced the rate of oxygen absorption, leading to increased glycolysis and mitochondrial protein synthesis. Therefore, oxygenated water is a potential adjuvant therapy or health food for treatment of hyperuricemia.

High Incidence of New-Onset Joint Pain in Patients on Fluoroquinolones as Antituberculous Treatment.

BACKGROUND: Joint pain is frequently observed in patients on antituberculous treatment, and pyrazinamide is known to be associated with joint pain in patients receiving antituberculous treatment. Fluoroquinolone-associated joint pain and tendon injury have been reported in long-term corticosteroid and transplant recipients, but data are lacking in patients with tuberculosis. OBJECTIVES: The objective of this study was to examine the incidence of joint pain manifested during administration of antituberculous therapy and their association with fluoroquinolones. METHODS: Patients diagnosed with tuberculosis attending the outpatient clinic over a period of 1 year were reviewed and divided into 3 groups: group A receiving pyrazinamide, group B receiving a fluoroquinolone, and group C receiving both pyrazinamide and a fluoroquinolone. Latency to onset of joint pain was noted in all 3 groups. Joint pain was initially managed with analgesics, and associated hyperuricemia was treated with allopurinol/febuxostat. Causative drugs were stopped in case of intolerable joint pain. RESULTS: 260 patients (47% females, aged 38 ± 18 years; mean ± SD) were included [group A (n = 140), group B (n = 81), and group C (n = 39)]. Overall, 76/260 (29%) patients developed joint pain: group A - 24/140 patients (17%), group B - 32/81 patients (40%), and group C - 20/39 patients (51%). The median latency to the onset of joint pain was 83 days (interquartile range, IQR 40-167): 55 days (IQR 32-66) in group A, 138 days (IQR 74-278) in group B, and 88 days (IQR 34-183) in group C. Hyperuricemia was present in 12/24 (50%) patients in group A and 11/20 (55%) patients in group C. Pyrazinamide was stopped in 7/140 (5%) patients in group A, fluoroquinolones in 6/81 (7%) patients in group B, and both pyrazinamide and fluoroquinolones were stopped in 5/39 (13%) patients in group C because of intolerable joint pain. Major joints affected were knees and ankles. CONCLUSION: There is a high incidence of joint pain in patients receiving antituberculous treatment, which is higher when fluoroquinolones or the pyrazinamide-fluoroquinolone combination are administered as compared to pyrazinamide alone.

Identifying mechanisms underlying the amelioration effect of Chrysanthemum morifolium Ramat. 'Boju' extract on hyperuricemia using biochemical characterization and UPLC-ESI-QTOF/MS-based metabolomics.

This study was aimed at evaluating the prospect of edible chrysanthemum extract as a potential substance for the prevention and treatment of hyperuricemia. Chrysanthemum morifolium Ramat. 'Boju' extract (CBE), which had the strongest xanthine oxidase inhibitory activity, showed a significant hypouricemic effect on potassium oxonate-induced hyperuricemic rats through inhibiting serum xanthine oxidase activity, regulating renal uric acid transport-related protein (ABCG2, URAT1 and GLUT9) expression and blood lipid levels, and protecting renal function. Serum metabolomics based on UPLC-ESI-QTOF/MS was used to illustrate mechanisms underlying the amelioration effect of CBE on hyperuricemia. A total of 35 potential biomarkers were identified. CBE prevented the pathological process of hyperuricemia by regulating 16/17 biomarkers associated with tryptophan, sphingolipid, glycerophospholipid and arachidonic acid metabolisms. CBE could alleviate hyperuricemia-related diseases including chronic kidney disease, hyperlipidemia and inflammation via reducing indoxyl sulfate, lysophosphatidylcholines and arachidonic acid levels, exhibiting its applicability and superiority in the treatment of hyperuricemia.

Dietary Antioxidant Supplements and Uric Acid in Chronic Kidney Disease: A Review.

Increased serum levels of uric acid have been associated with the onset and development of chronic kidney disease (CKD), cardiovascular disease, and mortality, through several molecular pathogenetic mechanisms, such as inflammation and oxidative stress. Oxidative stress is present even in the early stages of CKD, progresses parallelly with the deterioration of kidney function, and is even more exacerbated in end-stage renal disease patients undergoing maintenance hemodialysis. Although acting in the plasma as an antioxidant, once uric acid enters the intracellular environment; it behaves as a powerful pro-oxidant. Exogenous intake of antioxidants has been repeatedly shown to prevent inflammation, atherosclerosis and oxidative stress in CKD patients. Moreover, certain antioxidants have been proposed to exert uric acid-lowering properties. This review aims to present the available data regarding the effects of antioxidant supplements on both oxidative stress and uric acid serum levels, in a population particularly susceptible to oxidative damage such as CKD patients.

The Effects of Ginsenosides and Anserine on the Up-Regulation of Renal Aquaporins 1-4 in Hyperuricemic Mice.

Hyperuricemia is a metabolic disease of the kidney that results in decreased uric acid excretion. Here, we aimed to investigate the effects of ginsenosides and anserine on hyperuricemia and the expression of aquaporin (AQP) 1-4, which are indicators of renal excretion. Ginsenosides and anserine were administered separately or together after the establishment of hyperuricemia with adenine in BALB/c mice. Renal function indexes such as serum uric acid, creatinine, and urea nitrogen were measured in each group of mice, and the expression of AQP1-4 in renal tissues was detected. Serum uric acid and urea nitrogen were decreased in the ginsenoside and the anserine +UA groups. Meanwhile, the uric acid excretion and clearance rate were clearly increased in the co-treatment +UA group (p<0.05). Moreover, ginsenosides or anserine ginsenosides or anserine alone and treatment with both increased the expression of AQP1-4; however, the synergistic effects were more significantly enhanced (p<0.01). We provide the first reported evidence that ginsenosides and anserine have synergistic effects on uric acid excretion. The improvement in renal function in hyperuricemic mice after treatment with ginsenosides and anserine may result from up-regulation of AQP1-4 expressions.

Lychnophora pinaster ethanolic extract and its chemical constituents ameliorate hyperuricemia and related inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: Lychnophora pinaster, known as "Brazilian arnica" is used in folk medicine as alcoholic extract to treat inflammation, pain, rheumatism and bruises. AIM OF THE STUDY: Evaluate the effects of the Lychnophora pinaster's ethanolic extract and its chemical constituents on inflammation and hyperuricemia. MATERIALS AND METHODS: Ethanolic and hexanic extracts were obtained from the aerial parts of L. pinaster. Sesquiterpene E-lychnophoric acid was isolated from hexanic extract and identified by RMN, GC/MS and IR. In vivo anti-hyperuricemic and anti-inflammatory effects of the ethanolic extracts from L. pinaster (40, 125, 375 mg/kg), E-lychnophoric acid and other constituents previous isolated from L. pinaster and identified in the ethanolic extract by HPLC/UV/DAD (rutin, quercetin and vitexina flavonoids, caffeic, cinnamic and chlorogenic acids, lupeol and stigmasterol, at dose of 15 mg/kg) were assayed by experimental model of oxonate-induced hyperuricemia in Swiss mice, liver xanthine oxidase (XOD) inhibition and by MSU-induced paw edema in mice. RESULTS: Ethanolic extract and all its components presented anti-hyperuricemic activity by inhibiting the hepatic xanthine oxidase activity. Ethanolic extract and its chemical constituents, except quercetin and vitexin, were able to reduce paw edema size induced by urate crystals. Hypouricemic and anti-inflammatory results obtained for the ethanolic extract (40, 125, 375 mg/kg) and E-lychnophoric acid (15 mg/kg) were similar those obtained for standard drugs, allopurinol (10 mg/kg) and indomethacin (3 mg/kg). CONCLUSION: Ethanolic extract and E-lychnophoric, chlorogenic, cinnamic and caffeic acids, rutin, lupeol and stigmasterol presented anti-inflammatory and anti-hyperuricemic actvities. These compounds are responsible for the activities presented by the ethanolic extract of L. pinaster. Ethanolic extract and its chemical constituents can be considered promising agents in the therapeutic of inflammation, hyperuricemia and gout.

Highly Acylated Anthocyanins from Purple Sweet Potato ( Ipomoea batatas L.) Alleviate Hyperuricemia and Kidney Inflammation in Hyperuricemic Mice: Possible Attenuation Effects on Allopurinol.

Allopurinol is the first-line medication for hyperuricemia treatment. However, severe drug-related adverse effects have often been reported among patients who received allopurinol administration. This study is aimed at evaluating the possible attenuation effects of highly acylated anthocyanins from purple sweet potato (HAA-PSP) on hyperuricemia and kidney inflammation in hyperuricemic mice treated with allopurinol. In comparison with 5 mg kg-1 allopurinol used alone, the combination of 25 mg kg-1 HAA-PSP and 2.5 mg kg-1 allopurinol could not only reduce serum uric acid level in hyperuricemic mice but also attenuate the kidney damage, as indicated by the level of serum biomarkers as well as histopathological examination. The inflammatory response was partially mitigated by inhibiting the protein expression of typical cytokines in the kidney. Our findings provide new evidence for the supplementary therapeutic potential of HAA-PSP with allopurinol on hyperuricemia and inflammation-related syndromes. Moreover, this study provides a theoretical basis for assessing the potential of anthocyanin-rich foods in health.

Modified Chuanhu anti-gout mixture, a traditional Chinese medicine, protects against potassium oxonate-induced hyperuricemia and renal dysfunction in mice.

OBJECTIVE: Acute gout is a painful, inflammatory arthritis that features a rapidly escalating inflammatory response resulting from the formation of monosodium urate crystals in the affected joint space. Previously, we found that Chuanhu anti-gout mixture (CAGM) had similar effects as colchicine against gout in the clinic. Subsequently, to improve its effectiveness and efficacy, we modified the original formulation of CAGM. The current study evaluated the effectiveness of the modified formulation in mice. METHODS: Potassium oxonate (PO) was used to establish a mouse model of hyperuricemia. Plasma levels of uric acid and creatine were determined using the respective test kits. Hepatic xanthine oxidase (XOD) expression was examined by enzyme-linked immunosorbent assay. To explore the underlying mechanism, renal urate transporter 1 (URAT1) mRNA levels were evaluated by quantitative real-time PCR. Allopurinol and benzbromarone were used as reference drugs. RESULTS: The original CAGM and its modified high-dose formulation significantly reduced serum uric acid and creatine levels in hyperuricemic mice. In addition, the CAGM-treated groups displayed lower mRNA levels of hepatic XOD and renal URAT1. CONCLUSIONS: CAGM and its modified formulation significantly ameliorated PO-induced hyperuricemia in mice, which might be partially attributable to reductions of hepatic XOD and renal URAT1 levels.

Serum Uric Acid-Lowering Effects of Combined Glycine and Tryptophan Treatments in Subjects with Mild Hyperuricemia: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study.

We determined the serum uric acid-lowering effects of combined daily supplementation of glycine and tryptophan in patients with mild hyperuricemia using a randomized, double-blind, placebo-controlled, crossover clinical trial design. Japanese healthy adult males and females with mild hyperuricemia (fasting serum uric acid of 6.6⁻7.9 mg/dL) ingested a powder mixture containing 3.0 g of glycine and 0.2 g of tryptophan or a placebo powder once daily at bedtime for 6 weeks. Combined supplementation with glycine and tryptophan significantly decreased serum uric acid levels (from 7.1 mg/dL to 6.7 mg/dL, p = 0.004) before and after the trial. Serum uric acid concentrations significantly decreased in the subjects supplemented with the amino acid mixture compared with those in placebo-treated subjects (p = 0.028). In addition, the combination treatment with glycine and tryptophan decreased serum triglyceride levels (from 119 mg/dL to 86 mg/dL, p = 0.002). Increased solubility of uric acid caused by urinary pH were likely contributors to the serum uric acid-lowering effects of the amino acid mixture.

Study on the diagnosis of gout with xanthine and hypoxanthine.

BACKGROUND: Hyperuricemia is the only biochemical index in the classification of acute gouty arthritis in American Rheumatism Association 1977 and the main basis of clinical diagnosis for most doctors. However, nearly half of the time gout occurs without hyperuricemia, especially in an acute attack，which leads to an urgent need to find a new substitute diadynamic criteria of gout. Xanthine and hypoxanthine, as precursors of uric acid, have been reported to be high in gout patients with hyperuricemia and presumed to be gout biomarkers. OBJECTIVES: To further explore the possibility of xanthine and hypoxanthine to be gout biomarkers as substitutes for uric acid. METHODS: A reversed-phase HPLC-UV method was employed for simultaneous quantitative detection of uric acid (UA), xanthine (X), and hypoxanthine (HX) in gout patients' (with and without hyperuricemia) and healthy persons' serum. RESULTS: The xanthine and hypoxanthine concentrations in gout patients with hyperuricemia and without hyperuricemia are higher than in healthy persons with a P < 0.001. CONCLUSIONS: This study supplements previous researches by confirming that xanthine and hypoxanthine are significantly elevated in gout patients' serum especially in patients' with normouricemia, which supported xanthine and hypoxanthine may have clinical application for the diagnosis of gout.

Pterostilbene, a bioactive component of blueberries, alleviates renal fibrosis in a severe mouse model of hyperuricemic nephropathy.

Accumulating evidences indicated that hyperuricemia was an independent risk factor for kidney diseases and contributed to kidney fibrosis. Preventing and treating renal fibrosis was an optimal treatment for hyperuricemia-induced kidney diseases. In the study, pterostilbene (PTE) as a bioactive component of blueberries was confirmed to possess lowering serum uric acid and renal protective functions by the decrease of serum creatinine, BUN, urine albumin, and urine albumin-to-creatinine ratio (uACR) in a mouse model of hyperuricemic nephropathy (HN). Importantly, PTE treatment remarkably alleviated renal fibrosis of HN mice indicated by the downregulation of fibronectin, collagen I and α-SMA production. Furthermore, PTE could suppress the fibrosis-related protein expressions of TGF-ß1/Smad3, Src and STAT3 in the kidneys of HN mice. In conclusion, PTE suppressed the activation of TGF-ß1/Smad3, Src and STAT3 signaling pathway to alleviate renal fibrosis of HN mice, highlighting that PTE was a potential antifibrotic strategy for hyperuricemic nephropathy.