Herbal remedies in the management of hyperuricemia and gout: A review of in vitro, in vivo and clinical evidences.

Gout, or hyperuricemia is a multifactorial and multi-faceted metabolic disease that is quite difficult to manage and/or treat. Conventional therapies such as non-steroidal anti-inflammatory drugs (NSAIDs) such as allopurinol, corticosteroids and colchicine amongst others, have helped in its management and treatment to some extent. This study aimed to compile and analyze the different herbal remedies used in the management of hyperuricemia and gout. A literature search was conducted from key databases (PubMed, ScienceDirect, Cochrane Library, Google Scholar) using relevant keywords via the PRISMA model. Smilax riparia A.DC. from Traditional Chinese Medicine is used in many countries for its therapeutic effect on lowering serum urate levels. No single study was able to establish the efficacy of a specific traditionally used herb via in vitro, in vivo, and clinical studies. Patients were found to use a panoply of natural remedies, mainly plants to treat hyperuricemia and gout, which have been validated to some extent by in vitro, in vivo, and clinical studies. Nonetheless, further research is needed to better understand the ethnopharmacological relationship of such herbal remedies.

Signaling pathways in uric acid homeostasis and gout: From pathogenesis to therapeutic interventions.

Uric acid is a product of purine degradation, and uric acid may have multiple physiologic roles, including the beneficial effects as an antioxidant and neuroprotector, maintenance of blood pressure during low salt ingestion, and modulation of immunity. However, overproduction of metabolic uric acid, and/or imbalance of renal uric acid secretion and reabsorption, and/or underexcretion of extrarenal uric acid, e.g. gut, will contribute to hyperuricemia, which is a common metabolic disease. Long-lasting hyperuricemia can induce the formation and deposition of monosodium urate (MSU) crystals within the joints and periarticular structures. MSU crystals further induce an acute, intensely painful, and sterile inflammation conditions named as gout by NLRP3 inflammasome-mediated cleavage of pro-IL-1ß to bioactive IL-1ß. Moreover, hyperuricemia and gout are associated with multiple cardiovascular and renal disorders, e.g., hypertension, myocardial infarction, stroke, obesity, hyperlipidemia, type 2 diabetes mellitus and chronic kidney disease. Although great efforts have been made by scientists of modern medicine, however, modern therapeutic strategies with a single target are difficult to exert long-term positive effects, and even some of these agents have severe adverse effects. The Chinese have used the ancient classic prescriptions of traditional Chinese medicine (TCM) to treat metabolic diseases, including gout, by multiple targets, for more than 2200 years. In this review, we discuss the current understanding of urate homeostasis, the pathogenesis of hyperuricemia and gout, and both modern medicine and TCM strategies for this commonly metabolic disorder. We hope these will provide the good references for treating hyperuricemia and gout.

Coffee intake reduced gout risk by decreasing urate and urea while increasing SHBG levels in plasma: a mediation Mendelian randomization study.

OBJECTIVE: This study aims to investigate the causal relationships between specific dietary habits and the risk of gout, while identifying the mediators involved in these associations. METHODS: We initially assessed the causal effects of five dietary habits on gout by two-sample Mendelian randomization (MR). Subsequently, we identified mediators from five plasma metabolites by two-step MR, including urate, urea, sex hormone-binding globulin (SHBG), interleukin-18 (IL-18), and C-reactive protein (CRP). Next, we quantified the proportion of mediation effects by multivariable Mendelian randomization (MVMR). Last, we performed reverse MR analyses. Sensitivity analyses were conducted to enhance the robustness of our findings. RESULTS: Only coffee intake demonstrated a significant negative casual effect on gout (inverse variance weighted: OR = 0.444, p = 0.049). In two-step MR, coffee intake decreased urate and urea while increased SHBG levels, but did not affect IL-18 and CRP levels. Besides, urate and urea showed positive causal effects while SHBG exhibited a negative impact on gout. In mediation analysis, urate, urea, and SHBG respectively mediated 53.60%, 16.43%, and 4.81% of the total causal effect of coffee intake on gout. The three mediators collectively mediated 27.45% of the total effect. Reverse MR analyses suggested no significant reverse causal effects. Sensitivity analyses supported the reliability of our causal inferences. CONCLUSION: Coffee intake reduced gout risk by decreasing urate and urea while increasing SHBG levels in plasma. These findings accentuate the benefits of coffee intake for gout management. The mediators may provide a novel insight into potential therapeutic targets for gout prevention. Key Points • This study determines the causally protective effect of coffee intake on gout. • We reveal that coffee intake reduced the risk of gout by decreasing urate and urea while increasing SHBG levels in plasma. • Identifying specific mediators in the causal pathway from coffee intake to gout provides valuable information for clinical interventions of gout.

Elucidating the mechanism of the Tibetan medicine sanguotang in treating gouty arthritis through network pharmacology and in vivo experiments.

BACKGROUND: We explored the mechanisms of Sanguotang (SGT), a Tibetan medicine, in treating gout arthritis (GA). METHODS: The main active components, action targets, and disease targets of SGT were identified through TCMSP databases. The gene functions were analyzed using protein interaction (PPI) networks, Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and molecular docking. A GA model induced by monosodium urate was established in rats. The ankle joint swelling was observed. The levels of uric acid (UA) and albumin (ALB) in rat serum were measured. Hematoxylin and eosin (HE) staining was conducted to examine the pathological changes in rat ankle joints. RESULTS: Twenty-nine active components of SGT with proven efficacy and 66 intersection targets were identified, primarily involved in inflammation and immune regulation pathways. The PPI results revealed that the key targets of SGT against GA included ALB, IL6, TNF, TP53, and PTGS. Molecular docking showed favorable binding energy between the ALB protein and the active components. The results from animal experiments demonstrated that SGT effectively alleviated the inflammatory reaction in ankle joints, and decreased UA and ALB levels. Furthermore, SGT effectively inhibited the proliferation of synovial cells in the ankle joint cavity, prevented infiltration of inflammatory cells, and protected synovial tissue, thereby improving GA. CONCLUSIONS: SGT comprehensively contributes to the treatment of GA by regulating UA metabolism, reducing the release of inflammatory factors, and modulating immune and inflammatory pathways.

The effectiveness and safety of lifestyle medicine and integrative therapies in inflammatory arthritis: an umbrella review using a hierarchical evidence gathering approach.

Objective: An umbrella review was conducted to provide a comprehensive evaluation of the evidence on lifestyle medicine and integrative therapies for inflammatory arthritis. Methods: Five electronic databases were searched for umbrella reviews, meta-analyses, and systematic reviews of randomised controlled trials on acupuncture, diet, exercise, herbal medicine, nutrient supplements, and mind-body therapies for rheumatoid arthritis, spondyloarthritis, and gout published from January 2012 to December 2022. The primary outcomes were functional status and quality of life. Quality assessment was performed using the A MeaSurement Tool to Assess systematic Reviews (AMSTAR-2) tool, and the certainty of evidence for our primary outcomes was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach where possible. Results: We included 52 reviews. Exercise was beneficial for functional status in both rheumatoid arthritis and spondyloarthritis, with moderate certainty of evidence. Chinese herbal medicine in combination with disease-modifying anti-rheumatic drugs may improve functional status in rheumatoid arthritis (very low certainty evidence). Acupuncture may improve functional status in rheumatoid arthritis and pain in both rheumatoid arthritis and gout; however, the evidence is of very low certainty. Evidence for other therapies was not clinically significant; however, it suggests possible benefits from quercetin and polyunsaturated fatty acids. Yoga may result in a moderate improvement in functional status when used as an adjunct to medication; however, the certainty of evidence is very low. Diet interventions offered inconsistent improvements to functional status in rheumatoid arthritis, spondyloarthritis, and gout with low to very low certainty. Conclusion: Exercise should be prescribed for people with rheumatoid arthritis and spondyloarthritis. More research is needed to confirm or refute evidence for Chinese herbal medicine, acupuncture, yoga, and anti-inflammatory diets.

Screening and characterization of potential anti-gout components from Polygonum cuspidatum by integration off-line two-dimensional liquid chromatography-mass spectrometry with affinity ultrafiltration and on-line HPLC-ABTS.

Polygonum cuspidatum (P. cuspidatum) is a traditional herbal medicine with a long history and proven efficacy in treating gout. However, due to the complexity of composition and extensive content distribution, the substance basis of its anti-gout effectiveness is still unclear. A strategy was proposed via integrating off-line two-dimensional liquid chromatography (2D-LC) and targeted rapid screening technology based on ultrafiltration-liquid chromatography-mass spectrometry (UF-LC/MS) and on-line high-performance liquid chromatography-2, 2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (HPLC-ABTS) to accomplish high coverage and high throughput screening of anti-gout components from P. cuspidatum. As a result, twenty components were screened from P. cuspidatum extract with both xanthine oxidase (XOD) inhibitory activity and free radical scavenging activity, then were preliminarily identified by high-resolution electrospray ionization-quadrupole-time-of-flight mass spectrometer (ESI-Q-TOF/MS). The screened results were verified by the in vitro assays. Meanwhile, molecular docking further elucidated that the screened bioactive ingredients had favourable binding capabilities with XOD. The performance of this study can achieve high efficiency and high coverage screening of the anti-gout components from P. cuspidatum, which provides methodology and strategy support for the rapid screening of bioactive ingredients from complex medicinal plants.

Bioactive Phosphorus Dendrimers as a Universal Protein Delivery System for Enhanced Anti-inflammation Therapy.

Nanocarrier-based cytoplasmic protein delivery offers opportunities to develop protein therapeutics; however, many delivery systems are positively charged, causing severe toxic effects. For enhanced therapeutics, it is also of great importance to design nanocarriers with intrinsic bioactivity that can be integrated with protein drugs due to the limited bioactivity of proteins alone for disease treatment. We report here a protein delivery system based on anionic phosphite-terminated phosphorus dendrimers with intrinsic anti-inflammatory activity. A phosphorus dendrimer termed AK-137 with optimized anti-inflammatory activity was selected to complex proteins through various physical interactions. Model proteins such as bovine serum albumin, ribonuclease A, ovalbumin, and fibronectin (FN) can be transfected into cells to exert their respective functions, including cancer cell apoptosis, dendritic cell maturation, or macrophage immunomodulation. Particularly, the constructed AK-137@FN nanocomplexes display powerful therapeutic effects in acute lung injury and acute gout arthritis models by integrating the anti-inflammatory activity of both the carrier and protein. The developed anionic phosphite-terminated phosphorus dendrimers may be employed as a universal carrier for protein delivery and particularly utilized to deliver proteins and fight different inflammatory diseases with enhanced therapeutic efficacy.

Traditional Chinese medicine in the treatment of patients with hyperuricemia: A randomized placebo-controlled double-blinded clinical trial.

BACKGROUND: Studies have demonstrated the association of hyperuricemia with hypertension, metabolic syndrome, cardiovascular disease, and chronic renal disease. Although Western medicine presents promising effects for treating hyperuricemia and gout, identifying a safe and effective alternative to traditional Chinese medicine (TCM) for treating hyperuricemia is essential. OBJECTIVE: To evaluate the efficacy and safety of TCM formulas, "Wu-Ling San" and "Yin Chen Wu-Ling San," in patients with hyperuricemia. METHODS: A randomized, double-blinded, placebo-controlled clinical trial in adults with hyperuricemia was conducted. Sixty patients with serum urate level higher than 8 mg/dL were enrolled in the study. Patients were then randomized into three arms: "Wu-Ling San," "Yin Chen Wu-Ling San," and placebo for 4 weeks. Efficacy and safety were evaluated at weeks 2, 4, and 8. Primary and secondary endpoints were set to evaluate the serum urate concentration and related indicators at weeks 2, 4, and 8. RESULTS: No significant differences were observed among the three arms in terms of the serum urate level (<6 mg/dL) at week 4. The serum urate level was lower in the "Yin Chen Wi-Ling" arm at week 8 (8.1 mg/dL vs. 9.1 mg/dL, p = .034). The serum urate levels were significantly different in both the "Wu-Ling San" and "Yin Chen Wu-Ling San" arms from those at the baseline (p < .05). CONCLUSIONS: Two TCM formulas were found to be relatively safe for the short-term treatment of the patients with hyperuricemia. No statistically significant difference was observed in reaching the target-serum urate level <6 mg/dL.

Investigation of the mechanism of action of chemical constituents of celery seed against gout disease using network pharmacology, molecular docking, and molecular dynamics simulations.

Celery (Apium graveolens L.) has long been considered as a potential herbal medicine for the prevention and treatment of gout. However, the relationship between the chemical constituents and pharmacological activities of this medicinal plant has not been fully investigated yet. Therefore, this study aims to apply network pharmacology, molecular docking and molecular dynamics to explore the relationship between the chemical constituents of celery seed and its biological effects in the treatment of gout. Network pharmacology was built and analyzed based on the data collected from GeneCards, OMIM databases and SwissTargetPrediction web server using Cytoscape 3.9.0 software. The GO and KEGG pathway analysis of the potential targets of celery seed related to gout disease was performed using the ShinyGO v0.75 app. Molecular docking and molecular dynamics were carried out using Autodock vina and NAMD 2.14 software, respectively. The network analysis identified 16 active compounds and thirteen key targets of celery seed in the treatment of gout. The GO analysis and the KEGG pathway enrichment analysis suggested that the mechanism of action of the chemical constituents of celery seed might be involved in several pathways, notably the PI3K-Akt signaling pathway, Ras signaling pathway, and HIF-1 signaling pathway, respectively. Molecular docking and molecular dynamics revealed that apiumetin might be an important chemical that plays a key role in the pharmacological effect of celery seed. These results might be useful to select the Q-markers to control the quality of the products from celery seeds.Communicated by Ramaswamy H. Sarma.

Analyze the Laws and Mechanism of the National Patent Chinese Herbal Prescription for Gout / 浙江中医药大学学报

[Objective]To explore the medication rule of TCM compound patent in the treatment of gout,and analyze the mechanism of action of the core herbs based on the national patent database.[Methods]The Chinese herbal compound patent database for gout treatment was retrieved and entered into the Website of China Patent Announcement of The State Intellectual Property Office.The characteristics of medications were analyzed by frequency statistics,Apriori algorithm,factor analysis and systematic clustering method.The Chinese herbs targets of the core herbs combinations were obtained through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the gout disease targets were obtained from Human Gene database(GeneCards)and Online Mendelian Inheritance in Man(OMIM)database.The intersection of the two targets was imported into Cytoscape 3.9.1 software,and the Cluego plug-in was used to complete the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of the herb combinations.The intersection targets were imported into STRING database to obtain protein-protein interaction(PPI)network,and some key targets were selected for molecular docking with corresponding active compounds of Chinese herbs.[Results]A total of 508 Chinese herbal compound patents were included in the treatment of gout,involving 401 Chinese herbs,and the frequency of herbs was 6 082 times.Chinese herbs for diuresis-inducing and dampness-draining were mainly used,followed by herbs for tonifying deficiency,clearing heat,promoting blood circulation and removing blood stasis.The analysis of association rules obtained 3 binomial association rules and 5 trinomial association rules.Eight common factors were extracted by factor analysis.Three groups of herbs combinations were obtained by systematic clustering analysis,and 56 common biological pathways of herbs combination enrichment were found.Molecular docking results showed that the combination of Quercetin and tumor necrosis factor(TNF)was the best,followed by Baicalein and interleukin-6(IL-6),and the combination of Quercetin and adenosine triphosphate binding cassette super family G member 2(ABCG2)was good.[Conclusion]The national patent prescriptions for gout treatment based on the core pathogenesis of"turbid dampness and blood stasis"are mainly from three aspects of dampness,blood stasis and deficiency.The core herbs combinations are often supplemented or subtracted based on Simiao Powder,Fuling Zexie Decoction and Siwu Decoction.Chinese herbs mainly exert their effects through multiple signaling pathways such as TNF,hypoxia inducible factor-1(HIF-1),Toll-like receptors(TLRs)and IL-17 and promote excretion of uric acid.

TCM and related active compounds in the treatment of gout: the regulation of signaling pathway and urate transporter.

Gout represents a metabolic ailment resulting from the accumulation of monosodium urate crystals within joints, causing both inflammation and, harm to tissues. The primary contributor to gout's emergence is an elevated presence of serum urate, which is under the regulation of kidney and, gut urate transporters. Mitigating this risk factor is crucial for averting gout's onset. Several treatments rooted in TCM and related active compounds have demonstrated efficacy in managing gout, skillfully regulating serum uric acid (UA) levels and curbing inflammation's progression. This analysis compiles key foundational research concerning the molecular signaling pathways and UA transporters linked to gout, under the regulation of TCM. The focus includes individual botanical drug, active compounds, and TCM formulations, which have been consolidated and examined in this overview. The primary keywords chosen were "gout, hyperuricemia, gouty arthritis, traditional Chinese medicine, Chinese botanical drug, medicinal botanical drug, and natural plant". Various relevant literature published within the last 5 years were gathered from electronic databases, including PubMed, Web of Science, CNKI, and others. The findings revealed that TCM has the capacity to modulate various signaling pathways, including MAPK, NF-κB, PI3K/Akt, NLRP3 and JAK/STAT. Additionally, it impacts UA transporters like URAT1, GLUT9, ABCG2, as well as OATs and OCTs, thereby contributing to gout treatment. TCM helps maintain a balanced inflammatory interaction and facilitates UA excretion. This study enhances our understanding of TCM's anti-gout mechanisms and introduces novel perspectives for establishing the clinical significance and future prospects of TCM-based gout treatment.

Integrated Network Pharmacology and In-silico Approaches to Decipher the Pharmacological Mechanism of Dioscorea septemloba Thunb in Treating Gout and Its Complications.

BACKGROUND: Dioscorea septemloba Thunb. (DST) has demonstrated therapeutic potential in the treatment of gout and its associated complications. However, the underlying mechanisms of DST's pharmacological activity remain unclear. This study aims to investigate the pharmacological substances and network regulatory mechanisms of DST in treating gout and its complications using network pharmacology. METHODS: According to ultra-high performance liquid chromatography coupled with hybrid quadrupole-Orbitrap mass spectrometry (UPLC-Q-Exactive Orbitrap-MS) data and Lipinski's rule of five, 24 bioactive phytochemicals from DST were identified. The targets of gout were retrieved from Gene Expression Omnibus (GEO), GeneCards, and DisGeNET databases, followed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG pathway) enrichment analysis. The Cytoscape network analysis was used to identify the primary pathological pathways and key targets. Finally, LeDock was used for molecular docking to verify the active components of DST and their core target proteins. RESULTS: DST contains several core active ingredients, such as tetrahydroimidazo[1,2-a]pyridine- 2,5-dione, diosgenin, beta-sitosterol, dioscorol B, montroumarin and 9,10-dihydro-5,7- dimethoxy-3,4-phenanthrenediol. Moreover, these active components were found to strongly bind to the key targets for treating gout and its complications, including HSP90AA1, STAT3, PTGS2, PPARG, MTOR, HIF1A, MMP9, ESR1, and TLR4. As a result, DST alleviates gout and its complications by inhibiting xanthine dehydrogenase (XDH) to reduce uric acid levels and regulating the HIF-1α, EZH2/STAT3, and COX-2/PPAR-γ pathways to reduce inflammation. Additionally, it also plays an analgesic role by regulating the neuroactive ligand-receptor interaction pathway and calcium ion signaling pathway. CONCLUSION: This study has provided insights into the underlying mechanisms of DST in the treatment of gout and its complications, which could serve as a scientific foundation for its clinical translation.

Purple sweet potato (Ipomoea batatas L.) extract effects on levels of inflammatory markers and chondrocyte count in gout arthritis Wistar rat model.

BACKGROUND: Recently, herbal medicine has become alternative in management of gout. Our aim is to assess effectiveness of purple sweet potato extract in gout. METHOD: In vivo study with randomized posttest only control group design. Purple sweet potato extract administered to 16 Wistar rats with MSU-induced gout. Independent t-test for analyzing interleukin-1 ß (IL-1ß), matrix metalloproteinase-3 (MMP-3), cartilage oligomeric matrix protein (COMP), malondialdehyde (MDA), and number of chondrocytes results. RESULTS: Decreased level of IL-1ß (3.81 ± 1.54 ng/mL vs. 2.55 ± 0.59 ng/mL, p = 0.04), MDA (5.04 ± 1.02 ng/mL vs. 2.27 ± 0.57 ng/mL, p = 0.04), MMP-3 (5.66 ± 1.02 ng/mL vs. 3.84 ± 1.37 ng/mL, p = 0.01) COMP (21.01 ± 3.57 ng/mL vs. 17.27 ± 2.60 ng/mL, p = 0.03), and increasing chondrocytes (35.17 ± 12.35 lp vs. 48.56 ± 7.17 lp, p = 0.02). CONCLUSION: Purple sweet potato extract with anthocyanin inhibits inflammation and cartilage degeneration in gout. LEVEL OF EVIDENCE: Level 1.

A Review of Medicinal Plants and Phytochemicals for the Management of Gout.

Gout, characterized by elevated uric acid levels, is a common inflammatory joint disease associated with pain, joint swelling, and bone erosion. Existing treatments for gout often result in undesirable side effects, highlighting the need for new, safe, and cost-effective anti-gout drugs. Natural products, including medicinal plants and phytochemicals, have gained attention as potential sources of anti-gout compounds. In this review, we examined articles from 2000 to 2020 using PubMed and Google Scholar, focusing on the effectiveness of medicinal plants and phytochemicals in managing gout. Our findings identified 14 plants and nine phytochemicals with antigout properties. Notably, Teucrium polium, Prunus avium, Smilax riparia, Rhus coriaria, Foeniculum vulgare, Allium cepa, Camellia japonica, and Helianthus annuus exhibited the highest xanthine oxidase inhibitory activity, attributed to their unique natural bioactive compounds such as phenolics, tannins, coumarins, terpenoids, and alkaloids. Herbal plants and their phytochemicals have demonstrated promising effects in reducing serum urate and inhibiting xanthine. This review aims to report recent studies on plants/phytochemicals derived from herbs beneficial in gout and their different mechanisms.

Clustering of gout-related comorbidities and their relationship with gout flares: a data-driven cluster analysis of eight comorbidities.

OBJECTIVES: To study the aggregation of multiple comorbidities in people with gout and explore differences in prognosis of gout flares among different subgroups. METHODS: Hierarchical clustering was performed to identify homogeneous subgroups among 2639 people with gout using eight comorbidities. A one-year follow-up of acute gout flares in 463 of these people was conducted; the incidence and the timing of gout flares in each cluster were assessed to explore prognosis of gout flares. Binary logistic regression was applied to assess factors associated with gout flares. RESULTS: In baseline study, we identified five subgroups (C1-C5). C1 (n = 671, 25%) was characterized by isolated gout with few comorbidities. C2 (n = 258, 10%) were all obese. Almost all people in C3 (n = 335, 13%) had diabetes (99.7%). All people in C4 (n = 938, 36%) had dyslipidemia. C5 (n = 437, 17%) had the highest proportion of cardiovascular disease (CVD, 53%), chronic kidney disease (CKD, 56%), and cancer (7%). In follow-up study, C5 had the highest incidence (71.9%) and earliest onset (median 3 months) of gout flares. C2 had the lowest incidence (52.1%) and the latest onset (median 10 months) of gout flares. The highest relative risk for gout recurrent was seen for C5 (OR = 2.09). Other factors associated with the risk of gout flares were age at diagnosis of gout, duration of gout, presence of tophi, and smoking ≥ 20 cigarettes/day. CONCLUSIONS: We clustered people with gout into five groups with varying comorbidities. People with CVD, CKD, and cancer had the highest risk of gout flares and should receive comprehensive care.

Causal Association Between Tea Consumption and Gout: A Mendelian Randomization Study.

OBJECTIVE: Evidence from prospective studies on the consumption of tea and risk of gout is conflicting and limited. We aimed to investigate the potential causal effects of tea intake on gout using Mendelian randomization (MR). METHODS: Genome-wide association studies in UK Biobank included 349 376 individuals and successfully discovered single-nucleotide polymorphisms linked to consumption of one cup of tea per day. Summary statistics from the Chronic Kidney Disease Genetics consortium included 13 179 cases and 750 634 controls for gout. Two-sample MR analyses were used to evaluate the relationship between tea consumption and gout risk. The inverse-variance weighted (IVW) method was used for primary analysis, and sensitivity analyses were also conducted to validate the potential causal effect. RESULTS: In this study, the genetically predicted increase in tea consumption per cup was associated with a lower risk of gout in the IVW method (OR: 0.90; 95% CI: 0.82-0.98). Similar results were found in weighted median methods (OR: 0.88; 95% CI: 0.78-1.00), while no significant associations were found in MR-Egger (OR: 0.89; 95% CI: 0.71-1.11), weighted mode (OR: 0.80; 95% CI: 0.65-0.99), and simple mode (OR: 1.01; 95% CI: 0.75-1.36). In addition, no evidence of pleiotropy was detected by MR-Egger regression (P=0.95) or MR-PRESSO analysis (P=0.07). CONCLUSION: This study provides evidence for the daily consumption of an extra cup of tea to reduce the risk of gout.

Manganese-doped albumin-gelatin composite nanogel loaded with berberine applied to the treatment of gouty arthritis in rats via a SPARC-dependent mechanism.

In this study, manganese-doped albumin-gelatin composite nanogels (MAGN) were prepared and used to load berberine (Ber) for the treatment of gouty arthritis (GA). The nanodrug delivery system (Ber-MAGN) can target inflammatory joints due to the intrinsic high affinity of albumin for SPARC, which is overexpressed at the inflammatory site of GA. Characterization of the pharmaceutical properties in vitro showed that Ber-MAGN had good dispersion, and the particle size was 121 ± 10.7 nm. The sustained release effect significantly improved the bioavailability of berberine. In vitro and in vivo experimental results showed that Ber-MAGN has better therapeutic effects in relieving oxidative stress and suppressing inflammation. Therefore, Ber-MAGN, as a potential pharmaceutical preparation for GA, provides a new reference for the clinical treatment plan of GA.

Efficacy and safety of tart cherry supplementary citrate mixture on gout patients: a prospective, randomized, controlled study.

BACKGROUND: Low urine pH, which may be mediated by metabolic syndrome (MetS), is common in gout. Tart cherries are shown to improve MetS symptoms and possess anti-inflammatory properties. However, the efficacy of tart cherry supplements on urine pH has yet to be studied. OBJECTIVES: This study aimed to investigate the efficacy and safety of tart cherry supplementary citrate (TaCCi) mixture on urine pH, serum urate (sUA), C-reactive protein (CRP), and gout flares in gout patients initiating urate-lowering therapy (ULT), in comparison to citrate mixture and sodium bicarbonate. METHODS: A prospective, randomized (1:1:1), open-label, parallel-controlled trial was conducted among 282 men with gout and fasting urine pH ≤ 6, who were initiating ULT with febuxostat (initially 20 mg daily, escalating to 40 mg daily if serum urate ≥ 360 µmol/L). Participants were randomized to groups taking either sodium bicarbonate, citrate mixture, or TaCCi mixture. All participants were followed every 4 weeks until week 12. Urine pH and sUA were co-primary outcomes, with various biochemical and clinical secondary endpoints. RESULTS: Urine pH increased to a similar extent in all three groups. SUA levels declined in all three groups as well, with no significant differences observed between the groups. At week 12, the TaCCi mixture group exhibited a greater reduction in the urine albumin/creatinine ratio (UACR) compared to the other two groups (p < 0.05). Participants taking TaCCi mixture or citrate mixture experienced fewer gout flares than those in the sodium bicarbonate group over the study period (p < 0.05). Additionally, the TaCCi mixture group had a lower CRP level at week 12 relative to the other two groups (p < 0.01). Adverse events were similar across all three groups. CONCLUSION: The TaCCi mixture had similar efficacy and safety on urine alkalization and sUA-lowering as the citrate mixture and sodium bicarbonate in patients with gout. However, the TaCCi mixture resulted in greater improvements in UACR and CRP, which suggests that tart cherry supplements may provide additional benefits for renal protection and reduce inflammation in gout, particularly when starting ULT. TRIAL REGISTRATION: This project was registered in ChiCTR ( www.chictr.org.cn ), with the registration number: ChiCTR2100050749.

Yao-Shan of traditional Chinese medicine: an old story for metabolic health.

Type 2 diabetes mellitus, nonalcoholic fatty liver disease (NAFLD), cardio-cerebrovascular diseases (CCVDs), hyperuricemia and gout, and metabolic-related sexual dysfunction are metabolic diseases that affect human health in modern society. Scientists have made great efforts to investigate metabolic diseases using cell models in vitro or animal models in the past. However, the findings from cells or animals are difficult to translate into clinical applications due to factors such as the in vitro and in vivo differences; the differences in anatomy, physiology, and genetics between humans and animals; and the differences in microbiome-host interaction. The Chinese have extensively used the medicated diet of traditional Chinese medicine (TCM) (also named as Yao-Shan of TCM, Chinese Yao-Shan et al.) to maintain or improve cardiometabolic health for more than 2,200 years. These ancient classic diets of TCM are essential summaries of long-term life and clinical practices. Over the past 5 years, our group has made every effort to collect and sort out the classic Yao-Shan of TCM from the ancient TCM literature since Spring and Autumn and Warring States Period, especially these are involved in the prevention and treatment of metabolic diseases, such as diabetes, NAFLD, CCVDs, hyperuricemia and gout, and sexual dysfunction. Here, we summarized and discussed the classic Yao-Shan of TCM for metabolic diseases according to the time recorded in the ancient literature, and revised the Latin names of the raw materials in these Yao-Shan of TCM. Moreover, the modern medicine evidences of some Yao-Shan of TCM on metabolic diseases have also been summarized and emphasized in here. However, the exact composition (in terms of ratios), preparation process, and dosage of many Yao-Shan are not standardized, and their main active ingredients are vague. Uncovering the mystery of Yao-Shan of TCM through modern biological and chemical strategies will help us open a door, which is ancient but now looks new, to modulate metabolic homeostasis and diseases.