Background:Simiaowan(SMW),a well-known traditional Chinese medicine,has been employed to treat hyperuricemia(HUA)and gout for centuries.However,the bioactive components and underlying mechanisms have not been elucidat...Background:Simiaowan(SMW),a well-known traditional Chinese medicine,has been employed to treat hyperuricemia(HUA)and gout for centuries.However,the bioactive components and underlying mechanisms have not been elucidated.The objective of this study was to identify the active components and potential mechanisms of SMW by integrating pharmacological experimentation,serum pharmacochemistry,network pharmacology and molecular docking.Methods:HUA rats modelling by high-fat/high-sugar diet and potassium oxonate/adenine oral administration were used to evaluate the pharmacodynamic effects of SMW.UPLC-Q-Exactive-MS/MS was employed to detect the bioactive components present in SMW-containing serum.Network pharmacology and molecular docking were utilized to elucidate the potential targets and underlying mechanisms.Results:SMW effectively ameliorated HUA rats via the inhibition of uric acid(UA)production,promotion of UA excretion,improvement of lipid and glucose metabolic abnormalities,antioxidant,anti-inflammatory and anti-insulin resistance effects.A total of 73 compounds detected in SMW-containing serum were identified as potential active components,with alkaloids,flavonoids,organic acids,and terpenoids emerging as the primary active ingredients.Totally 203 corresponding targets were obtained as SMW anti-HUA/gout targets,which mainly participated in apoptosis,insulin resistance,TNF,PI3K-Akt,HIF-1,NF-κB,MAPK,IL-17 and TLR signaling pathways.Molecular docking indicated that active compounds(e.g.berberine,phellodendrine,quercetin,formononetin,ferulic acid)had superior binding abilities to the key targets(e.g.solute carrier family 22 member 12(URAT1),solute carrier family 22 member 6(OAT1),ATP-binding cassette sub-family G member 2(ABCG2),solute carrier family 2,facilitated glucose transporter member 9(GLUT9),xanthine dehydrogenase/oxidase(XDH),transcription factor p65(RELA),toll-like receptor 4(TLR4),prostaglandin G/H synthase 2(PTGS2),caspase-3(CASP3),insulin(INS)).Conclusion:SMW exerted regulatory influence over the disease network of HUA and gout through a multiplicity of components,targets,and pathways.Alkaloids,flavonoids,organic acids,and terpenoids were the primary active components,exerting anti-HUA/gout effects via antioxidant,anti-inflammatory,anti-insulin resistance,anti-apoptosis,inhibition of UA production,and promotion of UA excretion.This study revealed the active components and molecular mechanisms of SMW,providing insights into the development of natural products derived from SMW.展开更多
Globally,hyperuricemia is a growing health,social,and economic problem which could cause gout,chronic kidney diseases and other diseases.There are increasing evidences that a sensible diet makes sense to reduce the ri...Globally,hyperuricemia is a growing health,social,and economic problem which could cause gout,chronic kidney diseases and other diseases.There are increasing evidences that a sensible diet makes sense to reduce the risk of hyperuricemia.This review aims to explore the metabolic mechanism of dietary factors and effects of dietary types associated with hyperuricemia.Recommendations for dietary modification to prevent hyperuricemia are as following:decreasing intake of animal organs,seafood,sugar-sweetened,and alcohol beverages is essential;choosing water or unsweetened tea and coffee instead of sweetened beverages is beneficial;and increasing intake of vegetables,reduced-fat dairy products,foods containing fiber,micronutrients and unsaturated fatty acids is helpful.In addition,consumption of fruits and legumes in moderation is advantageous,and low-fructose of fruits and low-purine of non-soy beans are recommended.Moreover,personalized diet needs to be emphasized for hyperuricemic patients accompanied with diverse metabolic diseases.展开更多
Hyperuricemia(HUA)is characterized by elevated levels of uric acid(UA)in the bloodstream,resulting from either excessive production or insufficient excretion of UA within the body.If left untreated,progressive or pers...Hyperuricemia(HUA)is characterized by elevated levels of uric acid(UA)in the bloodstream,resulting from either excessive production or insufficient excretion of UA within the body.If left untreated,progressive or persistent HUA can lead to gout,causing significant harm to human health.Lactic acid bacteria(LAB),generally recognized as safe(GRAS)probiotics,have been shown to alleviate symptoms associated with gastrointestinal disorders such as irritable bowel syndrome and inflammatory bowel disease while supporting overall bodily functions and health.Recently,LAB has emerged as a potentially safe,cost-effective and efficient treatment for HUA.This comprehensive review aims to explore the current literature on the mechanisms through which LAB controls HUA.These mechanisms include suppressing purine metabolism,absorbing purine compounds,modulating microbiota to maintain host global purine homeostasis,reducing intestinal permeability,producing metabolites that alleviate HUA symptoms,promoting the expression of urate excretory proteins and inhibiting the expression of urate reabsorption proteins.The findings presented in this review provide a framework for further investigation into how probiotic LAB can alleviate HUA by influencing UA metabolism and elucidating their underlying action mechanisms.展开更多
BACKGROUND 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 metabol...BACKGROUND 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.AIM To explore the underlying mechanisms of Poecilobdella manillensis in HUA based on modulation of the gut microbiota and host metabolism.METHODS 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.RESULTS 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.CONCLUSION 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.展开更多
Hyperuricemia is a metabolic disorder caused by abnormal purine metabolism,resulting in abnormally high serum uric acid.In this study,a novel Levilactobacillus brevis PDD-5 isolated from salty vegetables was verified ...Hyperuricemia is a metabolic disorder caused by abnormal purine metabolism,resulting in abnormally high serum uric acid.In this study,a novel Levilactobacillus brevis PDD-5 isolated from salty vegetables was verified with the function of alleviating hyperuricemia.The relevant effects of L.brevis PDD-5 in lowering uric acid were analyzed by in vitro and in vivo experiments.The results showed that the L.brevis PDD-5 has(68.86±15.46)%of inosine uptake capacity and(95.75±3.30)%of guanosine uptake capacity in vitro.Oral administration of L.brevis PDD-5 to hyperuricemia rats reduced uric acid,creatinine,and urea nitrogen in serum,as well as decreased inosine and guanosine levels in the intestinal contents of rats.Analysis of relevant markers in the kidney by ELISA kits revealed that L.brevis PDD-5 alleviated oxidative stress and inflammation.Moreover,the gene expression of uric acid transporter 1(URAT1)and glucose transporter 9(GLUT9)was down-regulated,and the gene expression of organic anion transporter 1(OAT1)was up-regulated after treatment with L.brevis PDD-5.Western blot analysis showed that L.brevis PDD-5 alleviated hyperuricemia-induced kidney injury through the NLRP3 pathway.The se findings suggest that L.brevis PDD-5 can lower uric acid,repair kidney damage,and also has the potential to prevent uric acid nephropathy.展开更多
Hyperuricemia(HUA)is a vital risk factor for chronic kidney diseases(CKD)and development of functional foods capable of protecting CKD is of importance.This paper aimed to explore the amelioration effects and mechanis...Hyperuricemia(HUA)is a vital risk factor for chronic kidney diseases(CKD)and development of functional foods capable of protecting CKD is of importance.This paper aimed to explore the amelioration effects and mechanism of Andrias davidianus bone peptides(ADBP)on HUA-induced kidney damage.In the present study,we generated the standard ADBP which contained high hydrophobic amino acid and low molecular peptide contents.In vitro results found that ADBP protected uric acid(UA)-induced HK-2 cells from damage by modulating urate transporters and antioxidant defense.In vivo results indicated that ADBP effectively ameliorated renal injury in HUA-induced CKD mice,evidenced by a remarkable decrease in serum UA,creatinine and blood urea nitrogen,improving kidney UA excretion,antioxidant defense and histological kidney deterioration.Metabolomic analysis highlighted 14 metabolites that could be selected as potential biomarkers and attributed to the amelioration effects of ADBP on CKD mice kidney dysfunction.Intriguingly,ADBP restored the gut microbiome homeostasis in CKD mice,especially with respect to the elevated helpful microbial abundance,and the decreased harmful bacterial abundance.This study demonstrated that ADBP displayed great nephroprotective effects,and has great promise as a food or functional food ingredient for the prevention and treatment of HUA-induced CKD.展开更多
Hyperuricemia(HUA)is a condition associated with a high concentration of uric acid(UA)in the bloodstream and can cause gout and chronic kidney disease.The gut microbiota of patients with gout and HUA is significantly ...Hyperuricemia(HUA)is a condition associated with a high concentration of uric acid(UA)in the bloodstream and can cause gout and chronic kidney disease.The gut microbiota of patients with gout and HUA is significantly altered compared to that of healthy people.This article focused on the complex interconnection between alterations in the gut microbiota and the development of this disorder.Some studies have suggested that changes in the composition,diversity,and activity of microbes play a key role in establishing and progressing HUA and gout pathogenesis.Therefore,we discussed how the gut microbiota contributes to HUA through purine metabolism,UA excretion,and intestinal inflammatory responses.We examined specific changes in the composition of the gut microbiota associated with gout and HUA,highlighting key bacterial taxa and the metabolic pathways involved.Additionally,we discussed the effect of conventional gout treatments on the gut microbiota composition,along with emerging therapeutic approaches that target the gut microbiome,such as the use of probiotics and prebiotics.We also provided insights into a study regarding the gut microbiota as a possible novel therapeutic intervention for gout treatment and dysbiosis-related diagnosis.展开更多
BACKGROUND Patients with chronic heart failure(CHF)frequently develop hyperuricemia,an elevated serum uric acid level,associated with adverse outcomes.Dapagliflozin,a sodium-glucose cotransporter-2 inhibitor,demonstra...BACKGROUND Patients with chronic heart failure(CHF)frequently develop hyperuricemia,an elevated serum uric acid level,associated with adverse outcomes.Dapagliflozin,a sodium-glucose cotransporter-2 inhibitor,demonstrates reduction in cardiovascular mortality and hospitalization in patients with CHF and ejection fraction(HFrEF),irrespective of diabetes.However,dapagliflozin’s effect on the uric acid levels in patients with CHF and hyperuricemia remain unclear.AIM To investigate the effects of dapagliflozin on uric acid levels in CHF patients with hyperuricemia.METHODS We conducted a randomized,double-blind,placebo-controlled trial in 200 patients with CHF and hyperuricemia,with HFrEF and serum uric acid levels≥7 mg/dL(≥416μmol/L).The participants were randomly assigned to receive a daily dose of 10 mg dapagliflozin or placebo for 24 months.The primary endpoint was the change in serum uric acid level from baseline to 24 months.Secondary endpoints included changes in left ventricular ejection fraction(LVEF),Nterminal pro-B-type natriuretic peptide(NT-proBNP),and quality of life(QoL)scores,as well as the incidence of cardiovascular death and hospitalization for heart failure.RESULTS At 24 months,dapagliflozin significantly reduced serum uric acid levels by 1.2 mg/dL(71μmol/L)compared with placebo(95%CI:-1.5 to-0.9;P<0.001).Dapagliflozin also significantly improved LVEF by 3.5%(95%CI:2.1-4.9;P<0.001),NT-proBNP by 25%(95%CI:18-32;P<0.001),and QoL scores by 10 points(95%CI:7-13;P<0.001)and reduced the risk of cardiovascular death and hospitalization for heart failure by 35%(95%CI:15–50;P=0.002)compared with the placebo.Adverse events were similar between the two groups,except for a higher rate of genital infections in the dapagliflozin group(10%vs 2%,P=0.01).CONCLUSION Dapagliflozin significantly lowered serum uric acid levels and improved the clinical outcomes in patients with CHF and hyperuricemia.Therefore,dapagliflozin may be a useful therapeutic option for this high-risk population.展开更多
Hyperuricemia,a metabolic disorder related to uric acid metabolism dysregulation,has become a common metabolic disease worldwide,due to changes in lifestyle and dietary structure.In recent years,owing to their high ac...Hyperuricemia,a metabolic disorder related to uric acid metabolism dysregulation,has become a common metabolic disease worldwide,due to changes in lifestyle and dietary structure.In recent years,owing to their high activity and few adverse effects,food-derived active peptides used as functional foods against hyperuricemia have attracted increasing attention.This article aims to focus on the challenge associated with peptide-specific preparation methods development,functional components identification,action mechanism(s)clarification,and bioavailability improvement.The current review proposed recent advances in producing the food-derived peptides with high anti-hyperuricemia activity by protein source screening and matched enzymatic hydrolysis condition adjusting,increased the knowledge about strategies to search antihyperuricemia peptides with definite structure,and emphasized the necessity of combining computer-aided approaches and activity evaluations.In addition,novel action mechanism mediated by gut microbiota was discussed,providing different insights from classical mechanism.Moreover,considering that little attention was paid previously on the structure-activity relationships of anti-hyperuricemia peptides,we collected the sequences from published studies and make a preliminary summary about the structure-activity relationships,which in turn provided guides for enzymatic hydrolysis optimization and bioavailability improvement.Hopefully,this article could promote the development,application and commercialization of food-derived anti-hyperuricemia peptides in the future.展开更多
In this manuscript,we comment on the article by Liu et al published in the recent issue of the journal.Hyperuricemia(HUA)has become the second most common metabolic disease after type 2 diabetes mellitus and is the mo...In this manuscript,we comment on the article by Liu et al published in the recent issue of the journal.Hyperuricemia(HUA)has become the second most common metabolic disease after type 2 diabetes mellitus and is the most important risk factor for gout.This discussion focuses on the targets and clinical application value of traditional Chinese medicine(TCM)extracts in the treatment of HUA and gout,emphasizing the role of gut microbiota.Liu et al’s study demonstrated that Poecilobdella manillensis protein extract alleviated HUA through multiple mechanisms,including inhibition of uric acid(UA)reabsorption,promotion of UA excretion,repair of intestinal barrier function,and regulation of gut microbiota and metabolome.Unlike the commonly used urate-lowering drugs such as allopurinol and febuxostat,which have clear and single targets,many TCMs have multi-target effects.However,the active components and mechanisms of TCMs are not fully understood,limiting their clinical application in the treatment of HUA and gout.Additionally,the role of gut microbiota in UA metabolic homeostasis needs to be further explored.展开更多
Hyperuricemia is a high-risk factor for the development of gout and renal fibrosis,but the adverse effects of hyperuricemia on the liver have been seriously neglected.This research investigated the ameliorating effect...Hyperuricemia is a high-risk factor for the development of gout and renal fibrosis,but the adverse effects of hyperuricemia on the liver have been seriously neglected.This research investigated the ameliorating effect of Lacticaseibacillus rhamnosus Fmb14 on hyperuricemia induced liver dysfunction both in vitro and in vivo.Cell free extracts of high dose L.rhamnosus Fmb14 treatment reduced the death rate of HepG2 cell lines from 24.1%to 14.9%by inhibiting NLRP3 recruitment,which was mainly activated by reactive oxygen species release and mitochondrial membrane potential disorder.In purine dietary induced hyperuricemia(PDIH)mice model,liver oedema and pyroptosis were ameliorated after L.rhamnosus Fmb14 administration through downregulating the expression levels of NLRP3,caspase-1 and gasdermin-D from 1.61 to 0.86,3.15 to 1.01 and 5.63 to 2.02,respectively.L.rhamnosus Fmb14 administration restored mitochondrial inner membrane protein(MPV17)and connexin 43 from 2.83 and 0.73 to 0.80 and 0.98 respectively in PDIH mice,indicating that dysbiosis of mitochondrial membrane potential was restored in liver.Intriguingly,PDIH pyroptosis stimulates the process of apoptosis,which leads to severe leakage of hepatocytes,and both of pyroptosis and apoptosis were decreased after L.rhamnosus Fmb14 treatment.Therefore,L.rhamnosus Fmb14 is a promising biological resource to maintain homeostasis of the liver in hyperuricemia and the prevention of subsequent complications.展开更多
Objective:To investigate the efficacy and safety of Liqingtong(LQT)granules in patients with dampness-heat hyperuricemia.Methods:A randomized,double-blind,placebo-controlled pilot trial was conducted at the 983rd Hos-...Objective:To investigate the efficacy and safety of Liqingtong(LQT)granules in patients with dampness-heat hyperuricemia.Methods:A randomized,double-blind,placebo-controlled pilot trial was conducted at the 983rd Hos-pital of the Joint Logistic Support Force of the People's Liberation Army from March 15,2023,to August 10,2023.In total,119 participants were enrolled in this trial,and participants were given either LQT granules or placebo for 60 days based on a health education.The primary outcome was serum uric acid(SUA)level,and the secondary outcome was the traditional Chinese medicine(TCM)symptom score,measured on days 0,30,and 60.Safety indicators,including liver function,kidney function,blood routine,glucose,blood lipid,blood pressure,and heart rate were tested on days 0 and 60 of the trial.The data were analyzed using Prism 9 software,and the significance level was set at P<0.05.Results:Among 119 participants,six in the LQT granule group and seven in the placebo group dropped out,and 106 participants completed clinical observation.Baseline information,including SUA levels,TCM symptom scores,and other clinical characteristics,did not differ between the groups.At the end of the trial,compared with baseline values,the SUA levels in the LQT granule group decreased(P<0.001),and no significant change was observed in the placebo group(P=0.422);compared with the placebo group,the SUA levels decreased in the LQT granule group(P=0.001).Compared with baseline values,the total TCM symptom scores in the LQT granule group decreased(P<0.001),with no change in the placebo group(P=0.136).Safety indicators did not differ significantly between the two groups.Conclusion:The pilot trial demonstrated the potential of LQT granules to lower SUA levels and improve symptoms of dampness and heat.展开更多
Background:Hyperuricemia is a metabolic disorder which is characterized by increased serum uric acid levels,which can contribute to serious health issues such as gout,cardiovascular disease,and kidney damage.Epigeneti...Background:Hyperuricemia is a metabolic disorder which is characterized by increased serum uric acid levels,which can contribute to serious health issues such as gout,cardiovascular disease,and kidney damage.Epigenetic modifications,for example,DNA methylation,exert a crucial function in gene regulation and have been implicated in various metabolic disorders.The ATP-Binding Cassette Subfamily G Member 2(ABCG2)gene is involved in uric acid excretion,and its expression can be influenced by methylation of its promoter region.Methods:This study involved the design of three guide RNA(gRNA)sequences targeting specific CpG sites within the ABCG2 promoter region.Using the Clustered Regularly Interspaced Short Palindromic Repeats/dead Cas9-Ten-Eleven Translocation 1(CRISPR/dCas9-TET1)system,these gRNAs were employed to guide targeted demethylation of the ABCG2 promoter in cell models.A non-targeting gRNA served as a negative control.The methylation status of the ABCG2 promoter and its effect on gene expression were assessed using bisulfite sequencing and qRT-PCR.Results:Among the gRNAs tested,gRNA2 and gRNA3 effectively guided the dCas9-TET1 complex to the ABCG2 promoter,resulting in significant demethylation.gRNA2 showed the most pronounced effect,leading to a substantial increase in ABCG2 expression.Clinical data analysis revealed that adolescents with hyperuricemia had higher uric acid levels compared to healthy controls,and a higher proportion of the hyperuricemia group reported a high-protein diet,suggesting a link between diet and ABCG2 methylation.Conclusion:The findings demonstrate that targeted demethylation of the ABCG2 promoter can significantly upregulate its expression,which may help modulate uric acid levels.These results indicate that dietary factors,such as a high-protein diet,could influence ABCG2 methylation and thus impact hyperuricemia.Advanced research is necessary to explore the therapeutic potential of aiming at epigenetic modifications for the treatment of hyperuricemia.展开更多
Traditional Chinese medicine has a long and illustrious history,and with the development of modern science and technology,the research and application of traditional Chinese medicines have continued to progress signif...Traditional Chinese medicine has a long and illustrious history,and with the development of modern science and technology,the research and application of traditional Chinese medicines have continued to progress significantly.Many traditional Chinese medicinal herbs have undergone scientific validation,reinvi-gorating with new life and vitality,and contributing unique strengths to the advancement of human health.Recently,the discovery that leech total protein extracted from Poecilobdella manillensis lyophilized powder reduces blood uric acid(UA)levels by inhibiting the activity of xanthine oxidase to decrease UA synthesis and promotes UA excretion by regulating different UA transporters in the kidney and intestine has undoubtedly injected new vitality and hope into this field of research.The purpose of this editorial is to comment on this study,explore its strengths and weaknesses,and there is a hope to treat a range of metabolic-related syndromes,including hyperuricemia,by targeting the gut microbiota.展开更多
基金supported by Natural Science Foundation of Guangdong Province(2021A1515010978 and 2021A1515012474)Basic research project of Shenzhen Science and Innovation Commission(JCYJ20210324121610029)Guangdong Provincial Key Areas Research and Development Program project Lingnan TCM Modernization(2020B1111120003).
文摘Background:Simiaowan(SMW),a well-known traditional Chinese medicine,has been employed to treat hyperuricemia(HUA)and gout for centuries.However,the bioactive components and underlying mechanisms have not been elucidated.The objective of this study was to identify the active components and potential mechanisms of SMW by integrating pharmacological experimentation,serum pharmacochemistry,network pharmacology and molecular docking.Methods:HUA rats modelling by high-fat/high-sugar diet and potassium oxonate/adenine oral administration were used to evaluate the pharmacodynamic effects of SMW.UPLC-Q-Exactive-MS/MS was employed to detect the bioactive components present in SMW-containing serum.Network pharmacology and molecular docking were utilized to elucidate the potential targets and underlying mechanisms.Results:SMW effectively ameliorated HUA rats via the inhibition of uric acid(UA)production,promotion of UA excretion,improvement of lipid and glucose metabolic abnormalities,antioxidant,anti-inflammatory and anti-insulin resistance effects.A total of 73 compounds detected in SMW-containing serum were identified as potential active components,with alkaloids,flavonoids,organic acids,and terpenoids emerging as the primary active ingredients.Totally 203 corresponding targets were obtained as SMW anti-HUA/gout targets,which mainly participated in apoptosis,insulin resistance,TNF,PI3K-Akt,HIF-1,NF-κB,MAPK,IL-17 and TLR signaling pathways.Molecular docking indicated that active compounds(e.g.berberine,phellodendrine,quercetin,formononetin,ferulic acid)had superior binding abilities to the key targets(e.g.solute carrier family 22 member 12(URAT1),solute carrier family 22 member 6(OAT1),ATP-binding cassette sub-family G member 2(ABCG2),solute carrier family 2,facilitated glucose transporter member 9(GLUT9),xanthine dehydrogenase/oxidase(XDH),transcription factor p65(RELA),toll-like receptor 4(TLR4),prostaglandin G/H synthase 2(PTGS2),caspase-3(CASP3),insulin(INS)).Conclusion:SMW exerted regulatory influence over the disease network of HUA and gout through a multiplicity of components,targets,and pathways.Alkaloids,flavonoids,organic acids,and terpenoids were the primary active components,exerting anti-HUA/gout effects via antioxidant,anti-inflammatory,anti-insulin resistance,anti-apoptosis,inhibition of UA production,and promotion of UA excretion.This study revealed the active components and molecular mechanisms of SMW,providing insights into the development of natural products derived from SMW.
基金supported by the National Natural Science Foundation of China(No.32122069)Beijing Outstanding Young Scientist Program(No.BJJWZYJH01201910011025)China Postdoctoral Science Foundation(No.2023M730134)。
文摘Globally,hyperuricemia is a growing health,social,and economic problem which could cause gout,chronic kidney diseases and other diseases.There are increasing evidences that a sensible diet makes sense to reduce the risk of hyperuricemia.This review aims to explore the metabolic mechanism of dietary factors and effects of dietary types associated with hyperuricemia.Recommendations for dietary modification to prevent hyperuricemia are as following:decreasing intake of animal organs,seafood,sugar-sweetened,and alcohol beverages is essential;choosing water or unsweetened tea and coffee instead of sweetened beverages is beneficial;and increasing intake of vegetables,reduced-fat dairy products,foods containing fiber,micronutrients and unsaturated fatty acids is helpful.In addition,consumption of fruits and legumes in moderation is advantageous,and low-fructose of fruits and low-purine of non-soy beans are recommended.Moreover,personalized diet needs to be emphasized for hyperuricemic patients accompanied with diverse metabolic diseases.
基金funded by National Natural Science Foundation of China(32360564)the Natural Science and Technology Innovation Development Multiplication Plan of Guangxi University(2022BZRC010)。
文摘Hyperuricemia(HUA)is characterized by elevated levels of uric acid(UA)in the bloodstream,resulting from either excessive production or insufficient excretion of UA within the body.If left untreated,progressive or persistent HUA can lead to gout,causing significant harm to human health.Lactic acid bacteria(LAB),generally recognized as safe(GRAS)probiotics,have been shown to alleviate symptoms associated with gastrointestinal disorders such as irritable bowel syndrome and inflammatory bowel disease while supporting overall bodily functions and health.Recently,LAB has emerged as a potentially safe,cost-effective and efficient treatment for HUA.This comprehensive review aims to explore the current literature on the mechanisms through which LAB controls HUA.These mechanisms include suppressing purine metabolism,absorbing purine compounds,modulating microbiota to maintain host global purine homeostasis,reducing intestinal permeability,producing metabolites that alleviate HUA symptoms,promoting the expression of urate excretory proteins and inhibiting the expression of urate reabsorption proteins.The findings presented in this review provide a framework for further investigation into how probiotic LAB can alleviate HUA by influencing UA metabolism and elucidating their underlying action mechanisms.
基金Supported by National Natural Science Foundation of China,No.82160843.
文摘BACKGROUND 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.AIM To explore the underlying mechanisms of Poecilobdella manillensis in HUA based on modulation of the gut microbiota and host metabolism.METHODS 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.RESULTS 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.CONCLUSION 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.
基金the National Natural Science Foundation of China(31972048,32272339)the National Key R&D Program of China(2021YFD2100104)for financial support。
文摘Hyperuricemia is a metabolic disorder caused by abnormal purine metabolism,resulting in abnormally high serum uric acid.In this study,a novel Levilactobacillus brevis PDD-5 isolated from salty vegetables was verified with the function of alleviating hyperuricemia.The relevant effects of L.brevis PDD-5 in lowering uric acid were analyzed by in vitro and in vivo experiments.The results showed that the L.brevis PDD-5 has(68.86±15.46)%of inosine uptake capacity and(95.75±3.30)%of guanosine uptake capacity in vitro.Oral administration of L.brevis PDD-5 to hyperuricemia rats reduced uric acid,creatinine,and urea nitrogen in serum,as well as decreased inosine and guanosine levels in the intestinal contents of rats.Analysis of relevant markers in the kidney by ELISA kits revealed that L.brevis PDD-5 alleviated oxidative stress and inflammation.Moreover,the gene expression of uric acid transporter 1(URAT1)and glucose transporter 9(GLUT9)was down-regulated,and the gene expression of organic anion transporter 1(OAT1)was up-regulated after treatment with L.brevis PDD-5.Western blot analysis showed that L.brevis PDD-5 alleviated hyperuricemia-induced kidney injury through the NLRP3 pathway.The se findings suggest that L.brevis PDD-5 can lower uric acid,repair kidney damage,and also has the potential to prevent uric acid nephropathy.
基金financially supported by Shenzhen Agricultural Development Special Fund(Fishery)Agricultural High-Tech Project([2021]735)the Shenzhen Science and Technology Innovation Commission(KCXFZ20201221173207022)Youth Science Foundation Project(32101936)。
文摘Hyperuricemia(HUA)is a vital risk factor for chronic kidney diseases(CKD)and development of functional foods capable of protecting CKD is of importance.This paper aimed to explore the amelioration effects and mechanism of Andrias davidianus bone peptides(ADBP)on HUA-induced kidney damage.In the present study,we generated the standard ADBP which contained high hydrophobic amino acid and low molecular peptide contents.In vitro results found that ADBP protected uric acid(UA)-induced HK-2 cells from damage by modulating urate transporters and antioxidant defense.In vivo results indicated that ADBP effectively ameliorated renal injury in HUA-induced CKD mice,evidenced by a remarkable decrease in serum UA,creatinine and blood urea nitrogen,improving kidney UA excretion,antioxidant defense and histological kidney deterioration.Metabolomic analysis highlighted 14 metabolites that could be selected as potential biomarkers and attributed to the amelioration effects of ADBP on CKD mice kidney dysfunction.Intriguingly,ADBP restored the gut microbiome homeostasis in CKD mice,especially with respect to the elevated helpful microbial abundance,and the decreased harmful bacterial abundance.This study demonstrated that ADBP displayed great nephroprotective effects,and has great promise as a food or functional food ingredient for the prevention and treatment of HUA-induced CKD.
文摘Hyperuricemia(HUA)is a condition associated with a high concentration of uric acid(UA)in the bloodstream and can cause gout and chronic kidney disease.The gut microbiota of patients with gout and HUA is significantly altered compared to that of healthy people.This article focused on the complex interconnection between alterations in the gut microbiota and the development of this disorder.Some studies have suggested that changes in the composition,diversity,and activity of microbes play a key role in establishing and progressing HUA and gout pathogenesis.Therefore,we discussed how the gut microbiota contributes to HUA through purine metabolism,UA excretion,and intestinal inflammatory responses.We examined specific changes in the composition of the gut microbiota associated with gout and HUA,highlighting key bacterial taxa and the metabolic pathways involved.Additionally,we discussed the effect of conventional gout treatments on the gut microbiota composition,along with emerging therapeutic approaches that target the gut microbiome,such as the use of probiotics and prebiotics.We also provided insights into a study regarding the gut microbiota as a possible novel therapeutic intervention for gout treatment and dysbiosis-related diagnosis.
基金Supported by General Medical Research Fund Project,No.TYYLKYJJ-2022-025.
文摘BACKGROUND Patients with chronic heart failure(CHF)frequently develop hyperuricemia,an elevated serum uric acid level,associated with adverse outcomes.Dapagliflozin,a sodium-glucose cotransporter-2 inhibitor,demonstrates reduction in cardiovascular mortality and hospitalization in patients with CHF and ejection fraction(HFrEF),irrespective of diabetes.However,dapagliflozin’s effect on the uric acid levels in patients with CHF and hyperuricemia remain unclear.AIM To investigate the effects of dapagliflozin on uric acid levels in CHF patients with hyperuricemia.METHODS We conducted a randomized,double-blind,placebo-controlled trial in 200 patients with CHF and hyperuricemia,with HFrEF and serum uric acid levels≥7 mg/dL(≥416μmol/L).The participants were randomly assigned to receive a daily dose of 10 mg dapagliflozin or placebo for 24 months.The primary endpoint was the change in serum uric acid level from baseline to 24 months.Secondary endpoints included changes in left ventricular ejection fraction(LVEF),Nterminal pro-B-type natriuretic peptide(NT-proBNP),and quality of life(QoL)scores,as well as the incidence of cardiovascular death and hospitalization for heart failure.RESULTS At 24 months,dapagliflozin significantly reduced serum uric acid levels by 1.2 mg/dL(71μmol/L)compared with placebo(95%CI:-1.5 to-0.9;P<0.001).Dapagliflozin also significantly improved LVEF by 3.5%(95%CI:2.1-4.9;P<0.001),NT-proBNP by 25%(95%CI:18-32;P<0.001),and QoL scores by 10 points(95%CI:7-13;P<0.001)and reduced the risk of cardiovascular death and hospitalization for heart failure by 35%(95%CI:15–50;P=0.002)compared with the placebo.Adverse events were similar between the two groups,except for a higher rate of genital infections in the dapagliflozin group(10%vs 2%,P=0.01).CONCLUSION Dapagliflozin significantly lowered serum uric acid levels and improved the clinical outcomes in patients with CHF and hyperuricemia.Therefore,dapagliflozin may be a useful therapeutic option for this high-risk population.
基金sponsored by the National Natural Science Foundation China(32270115)National Key R&D Program of China(2018YFD0901102)+1 种基金Fundamental Research Funds for the Provincial Universities of Zhejiang(SJLY2021015)K.C.Wong Magna Fund of Ningbo University。
文摘Hyperuricemia,a metabolic disorder related to uric acid metabolism dysregulation,has become a common metabolic disease worldwide,due to changes in lifestyle and dietary structure.In recent years,owing to their high activity and few adverse effects,food-derived active peptides used as functional foods against hyperuricemia have attracted increasing attention.This article aims to focus on the challenge associated with peptide-specific preparation methods development,functional components identification,action mechanism(s)clarification,and bioavailability improvement.The current review proposed recent advances in producing the food-derived peptides with high anti-hyperuricemia activity by protein source screening and matched enzymatic hydrolysis condition adjusting,increased the knowledge about strategies to search antihyperuricemia peptides with definite structure,and emphasized the necessity of combining computer-aided approaches and activity evaluations.In addition,novel action mechanism mediated by gut microbiota was discussed,providing different insights from classical mechanism.Moreover,considering that little attention was paid previously on the structure-activity relationships of anti-hyperuricemia peptides,we collected the sequences from published studies and make a preliminary summary about the structure-activity relationships,which in turn provided guides for enzymatic hydrolysis optimization and bioavailability improvement.Hopefully,this article could promote the development,application and commercialization of food-derived anti-hyperuricemia peptides in the future.
基金Supported by Zhejiang Province Leading Geese Program,No.2024C03218Research Project of Jinan Microecological Biomedicine Shandong Laboratory,No.JNL-2023010Q.
文摘In this manuscript,we comment on the article by Liu et al published in the recent issue of the journal.Hyperuricemia(HUA)has become the second most common metabolic disease after type 2 diabetes mellitus and is the most important risk factor for gout.This discussion focuses on the targets and clinical application value of traditional Chinese medicine(TCM)extracts in the treatment of HUA and gout,emphasizing the role of gut microbiota.Liu et al’s study demonstrated that Poecilobdella manillensis protein extract alleviated HUA through multiple mechanisms,including inhibition of uric acid(UA)reabsorption,promotion of UA excretion,repair of intestinal barrier function,and regulation of gut microbiota and metabolome.Unlike the commonly used urate-lowering drugs such as allopurinol and febuxostat,which have clear and single targets,many TCMs have multi-target effects.However,the active components and mechanisms of TCMs are not fully understood,limiting their clinical application in the treatment of HUA and gout.Additionally,the role of gut microbiota in UA metabolic homeostasis needs to be further explored.
基金Grant support was received from the National Natural Science Foundation of China(32072182).
文摘Hyperuricemia is a high-risk factor for the development of gout and renal fibrosis,but the adverse effects of hyperuricemia on the liver have been seriously neglected.This research investigated the ameliorating effect of Lacticaseibacillus rhamnosus Fmb14 on hyperuricemia induced liver dysfunction both in vitro and in vivo.Cell free extracts of high dose L.rhamnosus Fmb14 treatment reduced the death rate of HepG2 cell lines from 24.1%to 14.9%by inhibiting NLRP3 recruitment,which was mainly activated by reactive oxygen species release and mitochondrial membrane potential disorder.In purine dietary induced hyperuricemia(PDIH)mice model,liver oedema and pyroptosis were ameliorated after L.rhamnosus Fmb14 administration through downregulating the expression levels of NLRP3,caspase-1 and gasdermin-D from 1.61 to 0.86,3.15 to 1.01 and 5.63 to 2.02,respectively.L.rhamnosus Fmb14 administration restored mitochondrial inner membrane protein(MPV17)and connexin 43 from 2.83 and 0.73 to 0.80 and 0.98 respectively in PDIH mice,indicating that dysbiosis of mitochondrial membrane potential was restored in liver.Intriguingly,PDIH pyroptosis stimulates the process of apoptosis,which leads to severe leakage of hepatocytes,and both of pyroptosis and apoptosis were decreased after L.rhamnosus Fmb14 treatment.Therefore,L.rhamnosus Fmb14 is a promising biological resource to maintain homeostasis of the liver in hyperuricemia and the prevention of subsequent complications.
基金funded by the National Key Research and Development Plan of the Traditional Chinese Medicine Modernization Research Key Project(2018YFC1706800).
文摘Objective:To investigate the efficacy and safety of Liqingtong(LQT)granules in patients with dampness-heat hyperuricemia.Methods:A randomized,double-blind,placebo-controlled pilot trial was conducted at the 983rd Hos-pital of the Joint Logistic Support Force of the People's Liberation Army from March 15,2023,to August 10,2023.In total,119 participants were enrolled in this trial,and participants were given either LQT granules or placebo for 60 days based on a health education.The primary outcome was serum uric acid(SUA)level,and the secondary outcome was the traditional Chinese medicine(TCM)symptom score,measured on days 0,30,and 60.Safety indicators,including liver function,kidney function,blood routine,glucose,blood lipid,blood pressure,and heart rate were tested on days 0 and 60 of the trial.The data were analyzed using Prism 9 software,and the significance level was set at P<0.05.Results:Among 119 participants,six in the LQT granule group and seven in the placebo group dropped out,and 106 participants completed clinical observation.Baseline information,including SUA levels,TCM symptom scores,and other clinical characteristics,did not differ between the groups.At the end of the trial,compared with baseline values,the SUA levels in the LQT granule group decreased(P<0.001),and no significant change was observed in the placebo group(P=0.422);compared with the placebo group,the SUA levels decreased in the LQT granule group(P=0.001).Compared with baseline values,the total TCM symptom scores in the LQT granule group decreased(P<0.001),with no change in the placebo group(P=0.136).Safety indicators did not differ significantly between the two groups.Conclusion:The pilot trial demonstrated the potential of LQT granules to lower SUA levels and improve symptoms of dampness and heat.
基金supported by the Science and Technology Plan Program of Yantian District of Shenzhen(YTWS20200208)Project funding department is Shenzhen Yantian District Science and Technology Innovation Bureau。
文摘Background:Hyperuricemia is a metabolic disorder which is characterized by increased serum uric acid levels,which can contribute to serious health issues such as gout,cardiovascular disease,and kidney damage.Epigenetic modifications,for example,DNA methylation,exert a crucial function in gene regulation and have been implicated in various metabolic disorders.The ATP-Binding Cassette Subfamily G Member 2(ABCG2)gene is involved in uric acid excretion,and its expression can be influenced by methylation of its promoter region.Methods:This study involved the design of three guide RNA(gRNA)sequences targeting specific CpG sites within the ABCG2 promoter region.Using the Clustered Regularly Interspaced Short Palindromic Repeats/dead Cas9-Ten-Eleven Translocation 1(CRISPR/dCas9-TET1)system,these gRNAs were employed to guide targeted demethylation of the ABCG2 promoter in cell models.A non-targeting gRNA served as a negative control.The methylation status of the ABCG2 promoter and its effect on gene expression were assessed using bisulfite sequencing and qRT-PCR.Results:Among the gRNAs tested,gRNA2 and gRNA3 effectively guided the dCas9-TET1 complex to the ABCG2 promoter,resulting in significant demethylation.gRNA2 showed the most pronounced effect,leading to a substantial increase in ABCG2 expression.Clinical data analysis revealed that adolescents with hyperuricemia had higher uric acid levels compared to healthy controls,and a higher proportion of the hyperuricemia group reported a high-protein diet,suggesting a link between diet and ABCG2 methylation.Conclusion:The findings demonstrate that targeted demethylation of the ABCG2 promoter can significantly upregulate its expression,which may help modulate uric acid levels.These results indicate that dietary factors,such as a high-protein diet,could influence ABCG2 methylation and thus impact hyperuricemia.Advanced research is necessary to explore the therapeutic potential of aiming at epigenetic modifications for the treatment of hyperuricemia.
文摘Traditional Chinese medicine has a long and illustrious history,and with the development of modern science and technology,the research and application of traditional Chinese medicines have continued to progress significantly.Many traditional Chinese medicinal herbs have undergone scientific validation,reinvi-gorating with new life and vitality,and contributing unique strengths to the advancement of human health.Recently,the discovery that leech total protein extracted from Poecilobdella manillensis lyophilized powder reduces blood uric acid(UA)levels by inhibiting the activity of xanthine oxidase to decrease UA synthesis and promotes UA excretion by regulating different UA transporters in the kidney and intestine has undoubtedly injected new vitality and hope into this field of research.The purpose of this editorial is to comment on this study,explore its strengths and weaknesses,and there is a hope to treat a range of metabolic-related syndromes,including hyperuricemia,by targeting the gut microbiota.
