Gout Research Articles

Phillyrin inhibits oxidative stress and neutrophil extracellular trap formation through the KEAP1/NRF2 pathway in gouty arthritis.

Gouty arthritis (GA) is an inflammatory disorder characterized by deposition of monosodium urate (MSU) crystal in joints. Phillyrin, a natural compound with anti-inflammatory properties, shows promise in mitigating inflammatory responses. This study investigates the therapeutic potential of phillyrin in GA and explores its mechanisms of action. GA was induced in mice via intraarticular MSU injection, and joint inflammation, inflammatory cell infiltration, and their level in serum/tissue were assessed. Key proteins in the NF-κB and NLRP3 pathways were examined using western blot analysis. The impact of phillyrin on oxidative stress, neutrophil extracellular trap (NET) formation, and neutrophil accumulation was evaluated by measuring CD11b + Ly6G + cells, MPO, CitH3, extracellular DNA ratio, and oxidative stress markers. In vitro studies assessed the effects of phillyrin on oxidative stress, cell viability, cytokine production, and NET formation in MSU-treated neutrophils. The KEAP1/NRF2 pathway's role was analyzed using ML385, an NRF2 inhibitor. Phillyrin significantly reversed MSU-induced ankle swelling and inflammatory cell infiltration in joint tissues. It suppressed pro-inflammatory cytokines and proteins in the NF-κB and NLRP3 pathways. Phillyrin reduced neutrophil infiltration, evidenced by lower MPO activity and NET formation, marked by reduced CitH3 expression. In vitro, phillyrin inhibited inflammatory marker expression and NET formation without affecting cell viability. It also restored antioxidant enzyme levels and reduced ROS production, regulating the KEAP1/NRF2 pathway, enhancing NRF2 expression and stability. These effects were reversed by NRF2 inhibition with ML385. Phillyrin alleviates GA by reducing joint inflammation, inhibiting NET formation, and suppressing oxidative stress through NRF2 modulation.

Bioactivity-Oriented Separation of "Pepper Alkaloids" from Piper sintenense Hatusima with Potential Antigouty Arthritis Activity.

Piper sintenense Hatusima (PsH) is a member of the Piper genus used as food and folk medicine in China. However, the detailed chemical ingredients and potential pharmacological effects are still underexploited. In this study, we evaluated the anti-inflammatory and antigouty arthritis effect of the ethanolic extract of P. sintenense. Active compounds were isolated from the petroleum ether fraction resulting in six novel amide alkaloids (1-6) and 13 known analogues (7-19). All of the compounds exhibited excellent anti-inflammatory activities. Bioinformatics analysis and in vitro experiments showed that compound 4 had anti-inflammatory properties (IC50 = 4.86 ± 0.32 μM) and antigouty arthritis activity. Mechanistic studies revealed that compound 4 exerted its favorable efficacy by regulating macrophage polarization by inhibiting P-STAT1/4. These findings provide new insights into the chemical composition and function of P. sintenense and expand its promising application as a functional food in the prevention and treatment of gouty arthritis.

Integrating metabolomics with network pharmacology to reveal the mechanism of Poria cocos in hyperuricemia treatment

Ethnopharmacological relevanceHyperuricemia is a chronic condition characterized by persistently elevated uric acid levels, often leading to gouty arthritis and renal insufficiency. Poria cocos F.A.Wolf, a traditional Chinese medicinal herb, possesses notable diuretic and anti-inflammatory properties and is widely used to treat edema, inflammation, viral infections, and tumors. Recent studies suggest that Poria cocos has the potential to lower uric acid levels and mitigate kidney damage, making it a promising candidate for hyperuricemia treatment. However, its pharmacological mechanisms require further exploration. Aim of the studyThis study aims to elucidate the mechanisms by which Poria cocos alleviates hyperuricemia, using metabolomics and network pharmacology approaches. Materials and methodsHyperuricemia was induced in rats via a high-yeast diet combined with potassium oxonate. The effects of Poria cocos were assessed by measuring serum uric acid, creatinine, urea nitrogen levels, hepatic xanthine oxidase activity, and renal tissue morphology. Non-targeted metabolomics was employed to identify differential metabolites and explore the metabolic pathways involved in its therapeutic effects. Network pharmacology was utilized to analyze potential targets and signaling pathways, which were validated through molecular docking and ELISA analysis. ResultsPoria cocos extract significantly reduced serum uric acid, creatinine, and urea nitrogen levels, inhibited xanthine oxidase activity, and attenuated kidney damage. Metabolomics combined with network pharmacology identified xanthine dehydrogenase and fatty acid synthase as key targets, while purine metabolism, fatty acid biosynthesis, and primary bile acid biosynthesis were identified as critical pathways. ELISA confirmed that Poria cocos suppressed xanthine dehydrogenase and fatty acid synthase expression in hyperuricemic rats. Molecular docking further verified strong binding interactions between core compounds and key targets. ConclusionsPoria cocos alleviates hyperuricemia by modulating multiple compounds, targets, and pathways. Through network pharmacology and metabolomics, it reveals that Poria cocos selectively regulates xanthine dehydrogenase and fatty acid synthase, influencing purine metabolism, fatty acid biosynthesis, and primary bile acid biosynthesis pathways. These findings provide insights into its therapeutic mechanisms, supporting the clinical application of Poria cocos in treating metabolic disorders and kidney damage associated with hyperuricemia.

Effective xanthine oxidase inhibitor urate lowering therapy in gout is linked to an emergent serum protein interactome of complement and inflammation modulators

Urate-lowering treatment (ULT) to target with xanthine oxidase inhibitors (XOIs) paradoxically causes early increase in gouty arthritis flares. Because delayed reduction in flare burden is mechanistically unclear, we tested for ULT inflammation responsiveness markers. Unbiased proteomics analyzed blood samples (baseline, 48 weeks ULT) in two, independent ULT out trial cohorts (n = 19, n = 30). STRING-db and multivariate analyses supplemented determinations of altered proteins via Wilcoxon matched pairs signed rank testing in XOI ULT responders. Mechanistic studies characterized proteomes of cultured XOI-treated murine bone marrow macrophages (BMDMs). At 48 weeks ULT, serum urate normalized in all gout patients, and flares declined in association with significantly altered proteins (p < 0.05) in clustering and proteome networks in sera and peripheral blood mononuclear cells. Sera demonstrated altered complement activation and regulatory gene ontology biologic processes. In both cohorts, a treatment-emergent serum interactome included key gouty inflammation mediators (C5, IL-1B, CXCL8, IL6). Last, febuxostat treatment decreased complement activation biologic process proteins in cultured BMDMs. Reduced gout flares are linked with a XOI treatment-emergent serum protein interactome that includes inflammation regulators, associated with altered complement activation and regulatory biologic processes. Serum and leukocyte proteomics could help identify when gouty inflammatory processes begin to subside in response to ULT.Trial Registration: ClinicalTrials.gov Identifier NCT02579096, posted October 19, 2015.

Therapeutic Potential of Methanolic Stem Extract of Costus afer on Serum Uric Acid, Tumor Necrosis Factor-alpha (TNF-α), and Interleukin-6 (IL-6) Levels in Monosodium Urate (MSU)-Induced Gouty Arthritis in Wistar Rats

The therapeutic potential of methanolic stem extracts of Costus afer was investigated to evaluate their effects on serum uric acid, TNF-α, and IL-6 levels, which are the key biomarkers associated with inflammatory and metabolic disorders like gouty arthritis. Qualitative and quantitative phytochemical analysis of C. afer indicated the presence of flavonoids, alkaloids, phenol, anthraquinone and glycosides, these bioactive compounds have been implicated for numerous medicinal uses and as such the therapeutic potentials of the extract were investigated by administering varying doses (100 mg/kg, 200 mg/kg, and 400 mg/kg) of the extract to a Wistar rat model with induced gouty arthritis and assessing its impact compared to a control group and an untreated MSU group. The results revealed that the extracts significantly reduced ( serum uric acid levels in a dose-dependent manner, with the high dose achieving a reduction below the control level. Additionally, the extracts effectively decreased ( TNF-α and IL-6 levels, indicating potent anti-inflammatory properties. The high dose exhibited the most substantial reduction in these biomarkers, underscoring the extract’s therapeutic potential. These findings support the traditional use of C. afer and provide scientific validation for its application in managing hyperuricemia and inflammatory conditions.

Advances in Gouty Arthritis Management: Integration of Established Therapies, Emerging Treatments, and Lifestyle Interventions.

Gouty arthritis, a prevalent inflammatory condition characterized by the deposition of monosodium urate crystals within joints, often results in debilitating pain and inflammation. Conventional therapeutic approaches, including nonsteroidal anti-inflammatory drugs, corticosteroids, and urate-lowering agents such as allopurinol and febuxostat, often have limitations such as adverse effects, drug interactions, and suboptimal patient compliance. This review presents a comprehensive overview of both established and emerging therapeutic strategies, developed between 2019 and 2024, for gouty arthritis; the review focuses on their mechanisms of action, efficacy, and safety profiles. Novel therapeutic approaches include pharmaceutical plant additives (e.g., Citrullus colocynthis, Atractylodes lancea), anti-inflammatory agents such as canakinumab and ozone therapy, and complementary therapies such as warm ginger compresses, Qingpeng ointment, and various lifestyle modifications. These strategies offer promising alternatives to conventional treatments by targeting uric acid metabolism, inflammatory pathways, and crystal formation, potentially reducing reliance on standard medications and minimizing adverse effects. Although therapies such as canakinumab have demonstrated significant efficacy in reducing gout flares, others such as polyphenol-rich foods offer favorable safety profiles. Further research, including large-scale clinical trials, is warranted to validate these findings and integrate these strategies into clinical practice to improve patient outcomes and quality of life.

A comparative randomised clinical trial of Amrutadi kwath and Vasadi kath in the management of Vatarakta (Gout)

Vatarakta specially occurs in Madhyavastha which is Parihanikala in which Dhatukshaya takes place. Khavaigunya (Rikta srotas) occurs in Asthi which is responsible for the production of Vatarakta. Vatarakta is a disease related with khavaigunya found in raktavaha strotas which include vitiated vata and rakta, so termed as vatarakta. Due to properties of sukshmatva and saratva of vayu, dravatva and saratva of rakta they spread all over the body. Symptoms of Vatarakta are shool, toda, daha, vaivarnya described by various acharya. Symptoms of Gouty arthritis are similar as of vatarakta Joint pain, Swelling, stiffness, disability and crepitations over small joint. Gouty arthritis is the most common form of arthritis, which occurs in middle age. Amrutadi Kwath and Vasadi Kwath have most of contents are snigdha, guru and mrudu. By virtue of these properties, this alleviates vata and pitta. Hence these are used in diseases which arise due to vitiation of vata and pitta. in vatarakta by its vatapittashamaka prabhav and snigddha, mrudu gunas by vatanulomana kriya. Amrutadi kwath is very effective in relieving the symptoms of vatarakta. Materials and Method: Total 80 patients of the age group 25-60 years presenting with signs and symptoms of vatarakta were selected randomly from OPD of the department of kayachiktsa. The 40 patients of trial group were treated with Amrutadi kwath and 40 patients of control group were subjected to vasadi kwath. Conclusion: Amrutadi Kwath showing significant results than Vasadi Kwath in symptoms of Vatarakta (Gout).

8802 A Rare Case Of Symptomatic Hypercalcemia In A Patient With Untreated Chronic Tophaceous Gout

Abstract Disclosure: S. Avula: None. A. Kumar: None. Z.J. Anderson: None. A. Chauhan: None. L.T. LaFave: None. Background: Hypercalcemia is a medical condition with abnormally high serum calcium levels. There are numerous mechanisms for the development of hypercalcemia, but gout is not well documented.Hypercalcemia attributed to Tophaceous gout is a rare phenomenon that is not well studied. Here we report a case of symptomatic hypercalcemia in a patient with a history of untreated tophaceous gout, leading to hypercalcemia and osteolytic lesions. Clinical Case: The patient is a 52-year-old male with a medical history of hypertension, rheumatoid arthritis, and tophaceous gout who immigrated from Tanzania. He presented with two weeks of abdominal pain that acutely worsened the morning of his presentation. He reported a 16-year history of tophaceous gout, for which he had been treated with allopurinol without success. On physical examination polyarticular subcutaneous nodules were present in the bilateral upper and lower extremities, primarily over the joints. There were similar lesions on the buttocks. Initial laboratory evaluation included a complete blood count which was notable for a hemoglobin of 10.3 g/dL (13.1 - 17.5 g/dL). His albumin was normal at 4 g/dl. (3.8 - 5.1 g/dl). Serum calcium was elevated at 12.9 mg/dL (8.8-10.0 mg/dL), with a serum ionized calcium level of 6.52 mg/dL(4.40-5.20 mg/dL). PTH was low at 15.8 pg/mL (16.0 - 65.0 pg/mL), and PTHrP was 2.9 pg/ml (&amp;lt;4.5 pg/ml). Uric acid level on admission was elevated to 11.4 mg/dL (3.4 - 7.0 mg/dL). 1-25 dihydroxy vitamin D elevated at 93.2 pg/mL (19.9 - 79.3 pg/mL). Computed tomography (CT) with intravenous contrast of the chest, abdomen, and pelvis was notable for axillary, pelvic, and inguinal lymphadenopathy concerning for lymphoproliferative or neoplastic processes. Biopsy of right inguinal node biopsy showed benign-appearing lymphoid tissue. Additional findings included multiple lobulated calcified hyperdense foci throughout the subcutaneous and muscular tissues of the buttocks with resorptive changes of the axial skeleton. Spectral CT reconstruction determined these to be uric acid deposits. Radiographs of his extremities were consistent with advanced gouty arthropathy. Infectious work-up was negative. Patient was given 3 liters of 0.9% sodium chloride. He received four doses of Calcitonin (4 units/kg) followed by one dose of Zoledronic acid 5 mg I.V. He was treated with Febuxostat, solumedrol and Azathioprine for his tophaceous gouty arthritis. Conclusion: Hypercalcemia is a commonly encountered yet a very important clinical condition. Parathyroid and malignant etiologies of hypercalcemia account for approximately 90% of cases of hypercalcemia. Gout as the inciting factor for developing hypercalcemia is a rarely documented phenomenon. This case highlights hypercalcemia as an unusual yet severe manifestation of untreated chronic gout and demonstrates the need for additional studies and reviews. Presentation: 6/2/2024

Evaluation of Community Pharmacist’s Knowledge, Attitudes, and Practices Regarding the Pharmacotherapy Management of Gouty Arthritis in Lahore, Pakistan

Background: Gouty arthritis is a prevalent but frequently misdiagnosed condition particularly in developing countries. As a medical expert pharmacists are essential to patient medication management, patient education, and treatment protocol adherence but insufficient information is present on related to gouty arthritis in Pakistan. Objective: The purpose of the study is to evaluate retail pharmacists (KAP) knowledge, attitude, practices regarding gouty arthritis in Lahore community pharmacies. It also examines the relationship between KAP scores and demographic characteristics finding gaps in pharmacist knowledge and treatment of arthritis. Methods: A study with a cross-sectional design was carried out on retail pharmacists working in community pharmacies throughout Lahore. Data on their knowledge attitude and practice regarding gouty arthritis were gathered using a structured questionnaire. The data were summarized using descriptive statistics. The Kolmogorov-Smirnov test evaluated normality, in addition to measures of skewness and kurtosis. Statistical analysis involved Fishers exact test and the Chi-square test to ascertain relationships between KAP scores and demographic factors. Effect size was measured using Cramer's V and Phi-square. Results: There is no significant association between demographics of pharmacists and knowledge. There is no association between our study variables and attitude. The post-hoc comparison of p values of different demographics shows no association with the practice regarding gouty arthritis. Conclusion: Despite their generally positive attitudes toward patient care community pharmacists have a notable knowledge gap regarding gouty arthritis. Enhanced training and education are required to improve community pharmacies handling of gout. Limitation such as sample size and response bias should be addressed in future research.

Serum ionized magnesium acts as an independent protective factor against bone erosion in patients with gouty arthritis: a cross-sectional study.

Gouty arthritis is a common inflammatory arthritis. The recurrent gout attacks severely damage the joint's function, lead to bone erosion, and affect bone metabolism. The role of magnesium (Mg) ions in bone homeostasis has been recognized, whereas its specific relationship with gouty bone erosion remains unclear. This study examined the association between serum ionized Mg levels and bone erosion in patients with gout arthritis. A total of 769 patients with gout arthritis were included in the study. Participants were classified into four groups based on the quartiles of the serum ionized Mg level. Logistic regression analysis assessed the association between serum ionized Mg and bone erosion. Compared to patients without bone erosion, serum ionized Mg levels were lower in gout patients with bone erosion (p<0.001). When dividing serum ionized Mg into quartiles, the prevalence rate of bone erosion in group Q1, representing the patients with the lowest serum ionized Mg levels, was notably higher than in Q2, Q3, and Q4 (60.2% vs. 43.6%, 45.6%, 40.3%, p<0.001). Multiple logistic regression analysis revealed that patients in Q2-Q4 had a lower odds ratio (OR) of bone erosion compared to those in Q1 (ORs were 0.520, 0.533, and 0.411 in Q2-Q4, respectively, p<0.001). The incidence of bone erosion is higher in gout arthritis patients with lower serum ionized Mg levels. High serum ionized Mg levels may be an independent protective factor for bone erosion in gout arthritis. Thus, Mg supplementation may be a promising approach to prevent or slow down the development of bone erosion in gouty arthritis.

The Therapeutic Potential of HMs in Acute Gouty Arthritis Through Immune Regulation

The Therapeutic Potential of HMs in Acute Gouty Arthritis Through Immune Regulation

UNFORESEEN BARRIER IN GOUT TREATMENT: A CASE OF COEXISTING LYME DISEASE

Refractory gout and Lyme disease are distinct conditions that, when coexisting, pose significant diagnostic and therapeutic challenges, particularly in regions endemic for Lyme disease. This case report presents a 49-year-old male with a three-year history of gout, presenting with acute arthritis of the first metatarsophalangeal joint, unresponsive to standard urate-lowering therapy. Despite treatment with colchicine and prednisone, the patient’s symptoms persisted, and inflammatory markers remained elevated. Imaging revealed findings consistent with gouty arthritis, but due to the atypical treatment response, further testing was conducted. Serological analysis confirmed infection with Borrelia burgdorferi, establishing the diagnosis of concurrent Lyme disease. The addition of doxycycline to the treatment regimen resulted in significant clinical improvement within days. This case highlights the importance of considering Lyme disease in patients with refractory gout in areas endemic for Lyme disease. While rare cases of Lyme disease mimicking gout have been reported, this is among the first documented instances of their coexistence. Early recognition and appropriate antibiotic treatment are critical in preventing complications and ensuring optimal management of both conditions.

Relationship Between Quality of Life and Compliance with the Management of Gouty Arthritis in Lanao, Philippines

Relationship Between Quality of Life and Compliance with the Management of Gouty Arthritis in Lanao, Philippines

Heart Rhythm Disturbances in Cardiac Surgery Patients with Coronary Artery Disease

The aim. To analyze arrhythmological complications in cardiac surgery patients with coronary artery disease (CAD). Materials and methods. This was a retrospective data analysis of 354 cardiac surgery patients with various forms of CAD who were operated on and discharged from the National Amosov Institute of Cardiovascular Surgery of the National Academy of Medical Sciences of Ukraine. The mean age of the patients was 61.9 ± 9.6 years. All the patients underwent laboratory examinations, electrocardiography, echocardiography, coronary angiography and cardiac surgery. The patients with uncomplicated forms of CAD (n = 194) underwent isolated surgical revascularization of the myocardium, in the case of complicated forms of CAD (n = 160), coronary bypass surgery was supplemented with valvular or ventricular correction. Results. Postoperative atrial fibrillation (AF) occurred in 40 (20.6%) patients with uncomplicated CAD and 43 patients with complicated CAD (26.8%), p = 0.1667. Among patients with complicated forms of CAD, 2 (1.25%) had paroxysms of ventricular tachycardia, which required the implantation of a cardioverter-defibrillator, also in this group of patients complete left bundle branch block occurred more often (p = 0.0020). The postoperative period in patients with impaired glucose metabolism was characterized by more frequent development of AF in patients with type 2 diabetes mellitus (33.3%, p = 0.0006), with impaired glucose tolerance (24.8%, p = 0.0156) compared to patients with normoglycemia (12.6%). Conclusions. There was no statistically significant difference in the frequency of postoperative AF in patients with various forms of CAD (p = 0.1667). In the occurrence of postoperative AF paroxysms, the negative influence of type 2 diabetes mellitus (p = 0.0006), impaired glucose tolerance (p = 0.0156), stage III-IV chronic kidney disease (p = 0.0015) and gouty arthritis (p = 0.0072) has been proven. The presence of postoperative AF was associated with acute encephalopathy (p = 0.0291) and panic attacks (p = 0.0043). The occurrence of postoperative AF increased the length of stay of cardiac surgery patients with CAD in the hospital from 8.2 ± 2.9 to 11.06 ± 6.8 days (p &lt; 0.0001).

Cell-based in vitro hemoassay for evaluation of NLRP3-inflammasome activity

Currently, gouty arthritis is considered as a polygenic multifactorial autoinflammatory disease caused by activation of the NOD (nucleotide-binding domain) -like protein receptor 3 inflammasome NLRP3. The two cytokines IL-1β and IL-18 are considered important biomarkers of NLRP3 inflammasome activation. However, usually the concentration of IL-1β in donor sera is extremely low and found to be at the limit of detection level (1-3 pg/ml), while the concentration of circulating cytokine IL-18 in the sera of individual donors varies greatly. This results in difficulty using these biomarkers in the diagnosis of autoinflammatory diseases. We hypothesized that the patient’s blood cells which were sensitized in vivo to the presence of specific factors characteristic of autoinflammatory diseases, in particular, gouty arthritis, would produce increased amounts of the inflammasome-regulated cytokines compared to blood cells obtained from healthy donors. A comparison of the IL-18 cytokine in healthy donors and patients with gouty arthritis was carried out using 2 methods: a) by traditional analysis of the level of serum circulated IL-18 and b) by using a cell-based Hemoassay in vitro developed at the research institute “Biotech” SamGMU. The comparative analysis demonstrated the advantages of using an in vitro cell-based Hemoassay to assess the IL-18 cytokine status of patients. Serum IL-18 values varied widely and showed no significant difference between donors and patients with gouty arthritis. Using the developed cell-based Hemoassay in vitro, significant quantitative differences in the production of the inflammatory cytokine IL-18 produced by blood cells of potentially healthy donors and patients with gouty arthritis were detected. Blood cells of individual patients, sensitized in vivo with specific factors characteristic of gouty arthritis, produce increased concentrations of IL-18 in the cell growth medium in vitro compared to cells from healthy donors. Thus, the in vitro cell-based Hemoassay can be used for a more accurate assessment of the cytokine status of patients.

Long-Term Evaluation of Allopurinol Effectiveness in the Thai Population: Insights from 10 Years of Real-World Big Data Analysis

Objective: This study aimed to evaluate the effectiveness and safety profile of allopurinol in Songklanagarind hospital, Thailand. Material and Methods: Electronic medical records (EMRs) of patients having undergone allopurinol treatment for gouty arthritis, or other pertinent indications, were retrospectively reviewed. The primary outcome of this study was the longitudinal measurement of uric acid levels. A linear mixed model (LMM) analysis assessed the statistical significance of uric acid reduction across hospital visits. The safety profile regarding allopurinol-related adverse drug reactions was assessed.Results: A total of 11,277 EMRs were extracted, of which 8,801 EMRs were eligible for further analyses. These records pertain to a cohort of 3,219 unique patients whose visits were arranged chronologically from the earliest to the fifth recorded visit. Overall, uric acid level decreased after allopurinol treatment in all patients. Across subsequent visits, the analysis, using LMM, found a significant reduction in uric acid levels (χ²=1465.4, df=4, p-value&lt;0.001), with the early reduction observed as early as the second visit. The incidence of allopurinol-related adverse reactions was 4.37% (385/8801 cases). Conclusion: The current dosing regimen of allopurinol at Songklanagarind Hospital has demonstrated favorable treatment outcomes and continues to be effective. This data provides insights into pharmacological management and its real-world outcomes.

Syn-COM: A Multi-Level Predictive Synergy Framework for Innovative Drug Combinations.

Drug prediction and treatment using bioinformatics and large-scale modeling have emerged as pivotal research areas. This study proposes a novel multi-level collaboration framework named Syn-COM for feature extraction and data integration of diseases and drugs. The framework aims to explore optimal drug combinations and interactions by integrating molecular virtuality, similarity clustering, overlap area, and network distance. It uniquely combines the characteristics of Chinese herbal medicine with clinical experience and innovatively assesses drug interaction and correlation through a synergy matrix. Gouty arthritis (GA) was used as a case study to validate the framework's reliability, leading to the identification of an effective drug combination for GA treatment, comprising Tamaricis Cacumen (Si = 0.73), Cuscutae Semen (Si = 0.68), Artemisiae Annuae Herba (Si = 0.62), Schizonepetae Herba (Si = 0.73), Gleditsiae Spina (Si = 0.89), Prunellae Spica (Si = 0.75), and Achyranthis Bidentatae Radix (Si = 0.62). The efficacy of the identified drug combination was confirmed through animal experiments and traditional Chinese medicine (TCM) component analysis. Results demonstrated significant reductions in the blood inflammatory factors IL1A, IL6, and uric acid, as well as downregulation of TGFB1, PTGS2, and MMP3 expression (p < 0.05), along with improvements in ankle joint swelling in GA mice. This drug combination notably enhances therapeutic outcomes in GA by targeting key genes, underscoring the potential of integrating traditional medicine with modern bioinformatics for effective disease treatment.

Clinical Versus Ultrasound Assessment of Joint Activity in Patients with Asymptomatic Hyperuricemia

Background: In this study, we aimed to investigate subclinical ultrasonographic change suggestive of gouty arthritis in the hyaline cartilage, joints and tendons from asymptomatic hyperuricemia (AH) individuals with hyperuricemia. Methods: We conducted a cross-sectional, observational study including US examinations of the knees and first MTPJs as well as of the tendons and enthesis. The normal distribution of different parameters was tested by the Shapiro–Wilk normality test. Quantitative data were expressed in mean ± standard deviation and the difference between means of two groups was tested by Student’s t-test while qualitative data were expressed in frequency and the difference between proportions was tested by the chi-square test or Fisher exact test. Results: Fifty-nine AH individuals and 52 normouricemic subjects were included. A total of 118 knees, ankles and first MTPJs in patients with AH and 104 in the normouricemic subjects were studied. The most common abnormality found on USG was power Doppler signal in 1st MTPJ (37% vs. 0%; P &lt; .001) followed by joint cavity widening (31% vs. 0%; P &lt; .001). Double contour sign was found in 11% of the first MTPJs from AH individuals versus none in the control group ( P &lt; .001). Posterior tibialis tenosynovitis (6% vs. 0%; P &lt; .01) and Achilles tendon enthesopathy (8% vs. 0%; P &lt; .001). Conclusions: These data demonstrate that subclinical changes detected in the US suggestive of gouty arthritis induced by chronic hyperuricemia frequently occur in both intra- and extra-articular structures of clinically AH individuals.

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

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

Exploration of the potential mechanism of Yiyi Tongfeng Formula in the treatment of acute gouty arthritis based on network pharmacology and molecular docking: A review.

The global prevalence of gout is on the rise. Yiyi Tongfeng Formula (YTF), a traditional herbal compound, has gained recognition for its efficacy in managing acute gouty arthritis (AGA). Despite its widespread use, the underlying mechanisms of YTF in AGA treatment remain largely undefined. This study employed network pharmacology and molecular docking to elucidate these mechanisms. We utilized the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, SymMap database, and various literature sources to identify active components and corresponding targets of YTF. Relevant AGA-associated targets were identified through the Genecards, Drugbank, Therapeutic Target Database, and Online Mendelian Inheritance in Man databases. A protein-protein interaction network was constructed to delineate interactions between YTF targets and AGA. Key ingredients and central targets were further analyzed using Cytoscape. Functional enrichment analyses, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, were conducted via Metascape. Additionally, molecular docking studies were performed using PyMOL and AutoDock4. It was found that quercetin, kaempferol, and luteolin may be the main active components of YTF for AGA treatment. Gene Ontology enrichment analysis shows that the main biological processes involved are cellular responses to lipids, and inflammatory responses. Kyoto Encyclopedia of Genes and Genomes enrichment analysis suggests the involvement of the IL-17 signaling pathway, AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, and so on. The findings suggest a multi-faceted therapeutic approach of YTF in treating AGA, involving multiple components, targets, biological processes, and signaling pathways. This comprehensive mechanism offers a foundation for further experimental validation.