scholarly journals Investigation of the Effects and Mechanisms of Dendrobium loddigesii Rolfe Extract on the Treatment of Gout

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Kai-hui Zhang ◽  
Mei-qi Wang ◽  
Lu-ling Wei ◽  
Cheng-jing Feng ◽  
Yu-si Zhang ◽  
...  
Keyword(s):  
Uric Acid ◽  
Acid Metabolism ◽  
Organic Anion ◽  
Gouty Arthritis ◽  
Organic Anion Transporter ◽  
Monosodium Urate ◽  
Acute Gouty Arthritis ◽  
Protein Levels ◽  
Anion Transporter ◽  
Uric Acid Transporters

Objective. Gout is a chronic disease that causes inflammatory arthritis, which is closely related to urate accumulation induced by a disorder of uric acid metabolism and the consequent deposition of monosodium urate crystals. Dendrobium loddigesii Rolfe is an herbal medicine that has been used in some traditional Chinese medicine formulae in the treatment of gout. This study aimed to explore and verify the antigout activity of Dendrobium loddigesii extract (DLE) on alleviating the hyperuricaemia of mice and the acute gouty arthritis of rats. Methods. An animal model of hyperuricaemia was established using potassium oxonate (PO). We analysed the expression of uric acid transporter mRNA in the kidney in the hyperuricaemic mice after treatment with DLE. Simultaneously, a monosodium urate crystal-induced acute gouty arthritis rat model was used to evaluate the effects of DLE, according to the level of ankle swelling, as well as the protein levels of inflammatory receptors and cytokines, as assayed by WB and ELISA. Results. DLE alleviated hyperuricaemia in mice and inhibited acute gouty arthritis in rats (P<0.05). Meanwhile, DLE regulated the levels of uric acid transporters mRNA transcripts, including mouse organic anion transporter 1 (mOAT1), organic anion transporter 3 (mOAT3), urate transporter 1 (mURAT1), and glucose transporter 9 (mGLUT9) in the kidney (P<0.05), suggesting that DLE promoted uric acid metabolism. Furthermore, DLE significantly suppressed the protein levels of TLRs, MyD88, and NF-κB in the ankle joint’s synovium (P<0.05), and the serum levels of IL-1β, IL-6, and TNF-α were also reduced, which demonstrated the anti-inflammatory effects of DLE. Conclusion. DLE alleviates hyperuricaemia by regulating the transcription level of uric acid transporters in the kidney. It also inhibits acute gouty arthritis by inhibiting the pathway of TLRs/MyD88/NF-κB in the ankle joint’s synovium. The findings of the present study imply that DLE alleviates gout by promoting uric acid metabolism and inhibiting inflammation related to the TLRs/MyD88/NF-κB pathway.

scholarly journals Tu-Teng-Cao Extract Alleviates Monosodium Urate-Induced Acute Gouty Arthritis in Rats by Inhibiting Uric Acid and Inflammation

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Rongmei Yao ◽  
Zihan Geng ◽  
Xin Mao ◽  
Yanyan Bao ◽  
Shanshan Guo ◽  
...  
Keyword(s):  
Uric Acid ◽  
Gouty Arthritis ◽  
Histological Evaluation ◽  
Therapeutic Effects ◽  
Monosodium Urate ◽  
Cell Degeneration ◽  
Acute Gouty Arthritis ◽  
Monosodium Urate Crystals ◽  
Potassium Oxonate ◽  
Urate Crystals

Gouty arthritis is an inflammatory joint disease closely related to hyperuricemia. It is characterized by deposition of monosodium urate crystals in the joints, resulting in an intense inflammatory process and pain. Control of hyperuricemia and anti-inflammation treatments are the main therapeutic approaches. However, the commonly used drugs for inhibiting uric acid and acute gouty arthritis have obvious gastrointestinal and renal toxicity; thus, there is an urgency to develop new alternative therapeutic drugs. An extract of Tu-Teng-Cao (TTC), a compound drug used in traditional Chinese medicine, has been widely applied to the clinical treatment of arthritis. In this study, we investigated the therapeutic effects of TTC on gouty arthritis. In this study, an animal model of acute gouty arthritis with hyperuricemia was established using potassium oxonate and monosodium urate crystals. After treatment with TTC, the results showed obvious therapeutic effects on the rat model of acute gouty arthritis. The treatment significantly attenuated the degree of ankle swelling, inflammation, and dysfunction index, and the levels of proinflammatory cytokines. In addition, TTC has significant antihyperuricemia activity in rats with hyperuricemia induced by potassium oxonate. Histological evaluation showed that TTC relieved pathological damage in rats with acute gouty arthritis induced by monosodium urate crystals. All the groups treated with TTC showed improvement in cartilage degeneration, cell degeneration, synovial hyperplasia, and inflammatory cell invasion in the ankle joint of rats. TTC significantly alleviated swelling, inflammation, and bleeding of the renal corpuscle and convoluted tubules of rats. The results of this study suggest that TTC is capable of treating gouty arthritis and decreasing ankle injury through the control of uric acid and inflammation.

scholarly journals Probenecid, a gout remedy, inhibits pannexin 1 channels

2008 ◽  
Vol 295 (3) ◽  
pp. C761-C767 ◽  
Author(s):  
William Silverman ◽  
Silviu Locovei ◽  
Gerhard Dahl
Keyword(s):  
Uric Acid ◽  
Organic Anion ◽  
Atp Release ◽  
Transport Processes ◽  
Organic Anion Transporter ◽  
Acid Excretion ◽  
Dye Uptake ◽  
Uric Acid Excretion ◽  
Pannexin 1 ◽  
Anion Transporter

Probenecid is a well-established drug for the treatment of gout and is thought to act on an organic anion transporter, thereby affecting uric acid excretion in the kidney by blocking urate reuptake. Probenecid also has been shown to affect ATP release, leading to the suggestion that ATP release involves an organic anion transporter. Other pharmacological evidence and the observation of dye uptake, however, suggest that the nonvesicular release of ATP is mediated by large membrane channels, with pannexin 1 being a prominent candidate. In the present study we show that probenecid inhibited currents mediated by pannexin 1 channels in the same concentration range as observed for inhibition of transport processes. Probenecid did not affect channels formed by connexins. Thus probenecid allows for discrimination between channels formed by connexins and pannexins.

scholarly journals Chinese Herbal Formulas Si-Wu-Tang and Er-Miao-San Synergistically Ameliorated Hyperuricemia and Renal Impairment in Rats Induced by Adenine and Potassium Oxonate

2015 ◽  
Vol 37 (4) ◽  
pp. 1491-1502 ◽  
Author(s):  
Yongping Guo ◽  
Qian Jiang ◽  
Dingkun Gui ◽  
Niansong Wang
Keyword(s):  
Uric Acid ◽  
Renal Impairment ◽  
Serum Uric Acid ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Protective Effects ◽  
Chinese Herbal ◽  
Renal Histopathology ◽  
Anion Transporter ◽  
Potassium Oxonate

Background/Aims: Hyperuricemia is an independent risk factor for chronic kidney disease and cardiovascular disease. Here, we examined the combined protective effects of Chinese herbal formula Si-Wu-Tang and Er-Miao-San on hyperuricemia and renal impairment in rats. Methods: Rats were randomly divided into normal rats, hyperuricemic rats, and hyperuricemic rats orally administrated with benzbromarone (4.5 mg·kg-1·d-1), Si-Wu-Tang (3.78 g·kg-1·d-1) and Si-Wu-Tang plus Er-Miao-San (6.48 g·kg-1·d-1) for 4 weeks. Hyperuricemic rats were orally gavaged with adenine (0.1 g·kg-1·d-1) and potassium oxonate (1.5 g·kg-1·d-1) daily for 4 weeks. Serum uric acid, creatinine, total cholesterol (TCH), triglyceride and blood urea nitrogen (BUN) concentrations, as well as urinary uric acid and microalbuminuria were measured weekly. Serum xanthine oxidase (XOD) activity and renal histopathology were also evaluated. The renal expression of organic anion transporter 1 (OAT1) and organic anion transporter 3 (OAT3) was detected by western blot. Results: Si-Wu-Tang plus Er-Miao-San lowered serum uric acid, creatinine, triglyceride and BUN levels to a greater degree than did Si-Wu-Tang alone. Si-Wu-Tang plus Er-Miao-San ameliorated microalbuminuria and renal histopathology, as well as decreased serum TCH concentration and XOD activity in hyperuricemic rats. Combination of Si-Wu-Tang and Er-Miao-San also led to a greater increase in OAT1 and OAT3 expression than did Siwutang alone. Conclusion: Si-Wu-Tang and Er-Miao-San synergistically ameliorated hyperuricemia and renal impairment in rats through upregulation of OAT1 and OAT3.

scholarly journals Active Components from Lagotis Brachystachya Maintain Uric Acid Homeostasis by Inhibiting Renal TLR4-NLRP3 Signaling in Hyperuricemic Mice

2021 ◽  
Author(s):  
Ji-Xiao Zhu ◽  
Hai-Yan Yang ◽  
Wei-Qiong Hu ◽  
Jie Cheng ◽  
Yang Liu ◽  
...  
Keyword(s):  
Uric Acid ◽  
Glucose Transporter ◽  
Organic Anion ◽  
Underlying Mechanism ◽  
Organic Anion Transporter ◽  
Active Components ◽  
Inflammatory Signaling ◽  
Anion Transporter ◽  
Glucose Transporter 9

Abstract Lagotis brachystachya Maxim is an herb widely used in traditional Tibet medicine. Our previous study indicated that total extracts from Lagotis brachystachya could lower uric acid levels. This study aimed to further elucidate the active components (luteolin, luteoloside and apigenin) isolated from Lagotis brachystachya and the underlying mechanism in vitro and vivo. The results showed that treatment with luteolin and luteoloside reversed the reduction of organic anion transporter 1 (OAT1) levels, while apigenin attenuated the elevation of urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) levels in uric acid-treated HK-2 cells, which were consistent with the finding in the kidney of potassium oxonate (PO)-induced mice. On the other hand, hepatic xanthine oxidase activity was inhibited by the components. In addition, all of these active components improved the morphology of the kidney in hyperuricemic mice. Moreover, molecular docking showed that luteolin, luteoloside and apigenin could bind TLR4 and NLRP3. Consistently, western blot showed that the components inhibited TLR4/MyD88/NLRP3 signaling. In conclusion, these results indicated that luteolin, luteoloside and apigenin could attenuate hyperuricemia by decreasing the production and increasing the excretion of uric acid, which were mediated by the inhibition of inflammatory signaling pathways.

scholarly journals Hypouricemic Effects of Chrysanthemum indicum L. and Cornus officinalis on Hyperuricemia-Induced HepG2 Cells, Renal Cells, and Mice

Plants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1668
Author(s):  
Ok-Kyung Kim ◽  
Jeong-Moon Yun ◽  
Minhee Lee ◽  
Dakyung Kim ◽  
Jeongmin Lee
Keyword(s):  
Uric Acid ◽  
Hepg2 Cells ◽  
Glucose Transporter ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Expression Levels ◽  
Cornus Officinalis ◽  
Anion Transporter ◽  
Chrysanthemum Indicum ◽  
Primary Mouse

Hyperuricemia, abnormally excess accumulation of uric acid, is caused by an imbalance between the production and excretion of uric acid and is a major cause of gout. We compared the effects of extracts from Chrysanthemum indicum L. (Ci) and Cornus officinalis Siebold and Zucc. (Co) on hyperuricemia, both individually and in combination (FSU-CC), using hypoxanthine-treated human liver cancer (HepG2) cells, primary mouse renal proximal tubule cells, and potassium oxonate induced hyperuricemic mice. The Ci contained 7.62 mg/g luteolin and 0 mg/g loganin, Co contained 0 mg/g luteolin and 4.90 mg/g loganin, and FSH-CC contained 3.95 mg/g luteolin and 2.48 mg/g loganin. We found that treatment with Ci, Co, and FSU-CC suppressed the activity of xanthine oxidase and mRNA expression of xanthine dehydrogenase while inducing an increase in the expression levels of the organic anion transporter 1 (OAT1) and organic anion transporter 3 (OAT3) proteins and a decrease in the expression levels of glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1) proteins. Particularly, treatment and supplementation with FSU-CC showed stronger effects than those of supplementation with either Ci or Co alone. We observed that the excretion of creatinine and uric acid in the combination of Ci and Co was higher than that observed in their individual supplementations and was similar to that of the normal group. Therefore, our data suggest that a combination of Ci and Co may potentially be used for the development of effective natural anti-hyperuricemic functional foods.

scholarly journals Pharmacologic Targeting of BET Proteins Attenuates Hyperuricemic Nephropathy in Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Chongxiang Xiong ◽  
Jin Deng ◽  
Xin Wang ◽  
Xiaofei Shao ◽  
Qin Zhou ◽  
...  
Keyword(s):  
Uric Acid ◽  
Epithelial To Mesenchymal Transition ◽  
Organic Anion ◽  
Mesenchymal Cell ◽  
Serum Levels ◽  
Organic Anion Transporter ◽  
Vimentin Expression ◽  
Mesenchymal Transition ◽  
Expression Levels ◽  
Anion Transporter

Hyperuricemia is an independent risk factor for renal damage and promotes the progression of chronic kidney disease. In this study, we investigated the effect of I-BET151, a small-molecule inhibitor targeting the bromodomain and extraterminal (BET) proteins, on the development of hyperuricemic nephropathy (HN), and the mechanisms involved. Expression levels of bromodomain-containing protein 2 and 4, but not 3 were increased in the kidney of rats with HN; administration of I-BET151 effectively prevented renal dysfunction, decreased urine microalbumin, and attenuated renal fibrosis as indicated by reduced activation of renal interstitial fibroblasts and expression of fibronectin and collagen I in HN rats. Mechanistic studies show that I-BET151 treatment inhibited transition of renal epithelial cells to a mesenchymal cell type as evidenced by preservation of E-cadherin and reduction of vimentin expression. This was coincident with reduced expression of TGF-β1 and dephosphorylation of Smad3 and ERK1/2. I-BET151 was also effective in inhibiting phosphorylation of NF-κB, expression of multiple cytokines and chemokines, and infiltration of macrophages to the injured kidney. Although there were increased serum levels of uric acid and xanthine oxidase, an enzyme that catalyzes production of uric acid, and decreased expression of renal organic anion transporter 1 and 3 that promote urate excretion in the model of HN, and reduced expression levels of urine uric acid, I-BET151 treatment did not affect these responses. Collectively, our results indicate that I-BET151 alleviates HN by inhibiting epithelial to mesenchymal transition and inflammation in association with blockade of TGF-β, ERK1/2 and NF-κB signaling.

scholarly journals Hypouricemic and Anti-oxidant Effects of Chrysanthemum indicum L. and Cornus officinalis In Vitro and In Vivo Models

2021 ◽  
Author(s):  
Ok-kyung Kim ◽  
Jeong Moon Yun ◽  
Minhee Lee ◽  
Dakyung Kim ◽  
Jeongmin Lee
Keyword(s):  
Uric Acid ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
In Vivo Models ◽  
Expression Levels ◽  
Cornus Officinalis ◽  
Anion Transporter ◽  
Chrysanthemum Indicum

Abstract Background: Hyperuricemia, abnormally excess accumulation of uric acid, is caused by an imbalance between the production and excretion of uric acid and is a major cause of gout. We compared the effects of extracts from Chrysanthemum indicum L. (Ci) and Cornus officinalis Siebold & Zucc (Co) on hyperuricemia, both individually and in combination (FSU-CC), Methods: We used hypoxanthine-treated human liver cancer (HepG2) cells and primary mouse renal proximal tubule cells for in vitro model, and potassium oxonate-induced hyperuricemic mice for in vivo model.Results: We found that treatment of Ci, Co, and FSU-CC suppressed the activity of xanthine oxidase and mRNA expression of xanthine dehydrogenase, while inducing an increase in the expression levels of the organic anion transporter 1 and organic anion transporter 3 proteins and a decrease in the expression levels of glucose transporter 9 and urate transporter 1 proteins. Particularly, treatment and supplementation with FSU-CC showed stronger effects than those of supplementation with either Ci or Co alone. We observed that the excretion of creatinine and uric acid in the combination of Ci and Co was higher than that observed in their individual supplementations and was similar to that of the normal group.Conclusions: Therefore, our data suggest that a combination of Ci and Co may potentially be used for the development of effective natural anti-hyperuricemic functional foods.

scholarly journals Organic Anion Transporter 5 Renal Expression and Urinary Excretion in Rats with Vascular Calcification

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
María Herminia Hazelhoff ◽  
Romina Paula Bulacio ◽  
Adriana Mónica Torres
Keyword(s):  
Urinary Excretion ◽  
Vascular Calcification ◽  
Western Blotting ◽  
Renal Injury ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Protein Levels ◽  
Anion Transporter ◽  
Male Wistar Rats ◽  
Renal Expression

It has been described renal damage in rats with vascular calcification. The organic anion transporter 5 (Oat5) is only expressed in kidney, and its urinary excretion was proposed as potential early biomarker of renal injury. The aim of this study was to evaluate the Oat5 renal expression and its urinary excretion in an experimental model of vascular calcification in comparison with traditional markers of renal injury. Vascular calcification was obtained by the administration of an overdose of vitamin D3(300,000 IU/kg, b.w., i.m.) to male Wistar rats. Oat5 urinary abundance was evaluated by Western blotting. Traditional markers of renal injury, such as creatinine and urea plasma levels, urinary protein levels, and urinary alkaline phosphatase (AP) activity, were determined using commercial kits. Histology was assessed by hematoxylin/eosin staining. Oat5 renal expression was evaluated by Western blotting and by immunohistochemistry. An increased expression of Oat5 in renal homogenates, in apical membranes, and in its urinary excretion was observed in rats with vascular calcification. The traditional parameters used to evaluate renal function were not modified, with the exception of histology. It is possible to postulate the urinary excretion of Oat5 as a potential noninvasive biomarker of renal injury associated with vascular calcification.

Effect of bempedoic acid on uric acid and gout in 3621 patients with hypercholesterolemia: pooled analyses from phase 3 trials

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K.K Ray ◽  
G.L Bakris ◽  
M Banach ◽  
A Catapano ◽  
P.B Duell ◽  
...  
Keyword(s):  
Uric Acid ◽  
Serum Uric Acid ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Lipid Lowering ◽  
Funding Source ◽  
Lipid Lowering Therapy ◽  
Private Company ◽  
Anion Transporter ◽  
History Of

Abstract Background Bempedoic acid (BA), an oral ATP-citrate lyase inhibitor, significantly lowers low-density lipoprotein cholesterol levels in patients with hypercholesterolemia. In clinical trials of BA, small mean increases in uric acid have been reported. BA weakly inhibits organic anion transporter 2 (OAT2) in vitro, which may account for small elevations in serum uric acid. Purpose To assess uric acid levels and incidence of gout with BA treatment. Methods Data were pooled from 4 randomized (2:1), double-blind studies of BA (180 mg daily) vs placebo for 12 weeks to 52 weeks in patients with hypercholesterolemia on stable background lipid-lowering therapy. Safety assessments included adverse events of special interest (elevation in uric acid levels, gout) and laboratory assessments. Results A total of 2424 patients treated with BA and 1197 patients on placebo were included in this analysis. Mean (SD) baseline uric acid levels were 6.0 (1.4) mg/dL for both groups. History of gout was reported by 5.2% (127/2424) and 5.8% (69/1197) in the BA and placebo groups, respectively. At week 12, mean (SD) serum uric acid levels (% change from baseline) increased from baseline with BA treatment by 0.82 (0.97) mg/dL (14.8%) vs –0.02 (0.82) mg/dL (0.67%) for placebo. Elevations in serum uric acid levels typically occurred within the first 4 weeks of treatment, remained stable during treatment, and returned to baseline after treatment discontinuation. Gout was reported in 1.4% (BA) and 0.4% (placebo) of patients, and hyperuricemia was reported in 1.7% (BA) and 0.6% (placebo) of patients. Other potential clinical consequences of elevated uric acid levels (eg, events associated with nephrolithiasis), were similar between groups (0.7% vs 0.8%). In both groups, patients who reported gout during the studies were more likely to have a medical history of gout or elevated baseline uric acid levels (Table). Few patients discontinued treatment due to gout (n=1, &lt;0.1% [BA]) or uric acid increases (n=2, &lt;0.1% [BA]). Conclusion Mean increases in uric acid levels were small, remained stable while patients continued to receive treatment, were infrequently associated with AEs, and were reversible on discontinuation of BA Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Esperion Therapeutics funded the research for this study and provided writing support for this abstract. Medical writing assistance was provided by Agnella Izzo Matic, PhD, CMPP, and Kelly M Cameron, PhD, CMPP, of JB Ashtin.

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