scholarly journals Traditional Uighur Medicine Karapxa decoction, inhibits liver xanthine oxidase and reduces serum uric acid concentrations in hyperuricemic mice and scavenges free radicals in vitro

Author(s):  
Nurmuhammat Amat ◽  
Anwar Umar ◽  
Parida Hoxur ◽  
Mihrigul Anaydulla ◽  
Guzalnur Imam ◽  
...  
Planta Medica ◽  
2017 ◽  
Vol 83 (17) ◽  
pp. 1335-1341 ◽  
Author(s):  
Jin Kim ◽  
Woo Kim ◽  
Jung Hyun ◽  
Jong Lee ◽  
Jin Kwon ◽  
...  

AbstractHyperuricemia is a clinical condition characterized by an elevated level of serum uric acid and is a key risk factor for the development of gout and metabolic disorders. The existing urate-lowering therapies are often impractical for certain patient populations, providing a rationale to explore new agents with improved safety and efficacy. Here, we discovered that Salvia plebeia extract inhibited the enzyme activity of xanthine oxidase, which is a key enzyme generating uric acid in the liver. In an animal model of hyperuricemia, S. plebeia extract reduced serum urate to the levels observed in control animals. The urate-lowering effect of S. plebeia extract in vivo was supported by the identification of compounds that inhibit xanthine oxidase enzyme activity in vitro. Nepetin, scutellarein, and luteolin contributed significantly to S. plebeia bioactivity in vitro. These compounds showed the highest potency against xanthine oxidase with IC50 values of 2.35, 1.74, and 1.90 µM, respectively, and were present at moderate quantities. These observations serve as a basis for further elaboration of the S. plebeia extracts for the development of new therapeutics for hyperuricemia and related diseases.


2016 ◽  
Vol 7 (10) ◽  
pp. 4239-4246 ◽  
Author(s):  
Jhih-Jia Jhang ◽  
Jia-Wei Ong ◽  
Chi-Cheng Lu ◽  
Chin-Lin Hsu ◽  
Jia-Hong Lin ◽  
...  

Uric acid is a metabolite obtained from purine by xanthine oxidase activity (XO) and high levels of serum uric acid leads to hyperuricemia and gout.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 474-474
Author(s):  
Yoshiki Shimizu ◽  
Tsuyoshi Sakurada ◽  
Sayuri Matsuoka ◽  
Kei Yui ◽  
Takayuki Hosoi

Abstract Objectives This study was aimed to evaluate the effect of vine tea extract (VE) which contained ampelopsin (AMP) on postprandial serum uric acid levels. Methods A randomized, placebo controlled, and crossover study was performed from January 2018 to June 2018. The participants were Japanese male whose fasting serum uric acid levels were between 5.0 mg/dL and 7.0 mg/dL. The purine (RNA) loading test was conducted in this study. In brief, after fasting blood collection, the subjects ingested 4 g of yeast RNA and trial supplements (500 mg of VE (150 mg of AMP) or placebo), their blood and urine were subsequently collected every 1 hr for 4 hr. Uric acid and creatinine (Cr) levels in the blood and urine were measured. The primary outcome was postprandial uric acid area under the curve (AUC) and the secondary outcomes were postprandial uric acid, Cr clearance, urinary uric acid excretion, uric acid clearance, and fractional excretion of uric acid (FEUA). To investigate the urate lowering mechanism of VE, effect of VE or AMP on xanthine oxidase (XO) and urate transporter function was assessed in vitro. Results Of 119 participants screened, 36 males who met inclusion criteria were enrolled and the subjects were randomly assigned to two groups. Of these, 16 in X group and 18 in Y group were completed of the study. The values were expressed as mean ± SE. The postprandial uric acid AUC of VE (199.14 ± 62.38 mg · min/dL) was lower than that of placebo (214.41 ± 66.91 mg · min/dL), but it was not significant (P = 0.166). On the other hand, intake of VE induced the increase of urinary uric acid excretion (180 min; VE 0.58 ± 0.03 mg/kg/hr; P0.52 ± 0.03 mg/kg/hr; P = 0.044) and FEUA (180 min; VE 0.58 ± 0.03 mg/kg/hr; P 0.52 ± 0.03 mg/kg/hr; P = 0.044). These results suggest VE facilitate the uric acid excretion. An exploratory efficacy analysis was performed on 23 subjects whose eGFR values were less than 89 mL/min. As a result, the intake of VE suppressed postprandial uric acid elevation in those subjects significantly. AMP and VE inhibited the activity of XO in vitro. In addition, AMP weakly inhibited the function of OAT4, one of the urate reabsorption transporters. Conclusions These results suggested that intake of VE inhibited uric acid synthesis and facilitated of urate excretion, thereby suppression of the elevation of postprandial serum uric acid was observed. Funding Sources This study was supported by FANCL Corporation.


2008 ◽  
Vol 36 (01) ◽  
pp. 149-157 ◽  
Author(s):  
Cai Guo Huang ◽  
Yan Jun Shang ◽  
Jun Zhang ◽  
Jian Rong Zhang ◽  
Wen Jie Li ◽  
...  

Phenylpropanoid glycoside acteoside was extracted from the traditional Chinese medicine Scrophularia ningpoenis Hemsl. In the present study, we investigated the effects of acteoside administration on serum uric acid levels in mice rendered hyperuricemic with the uricase inhibitor potassium oxonate. When administered orally for 3 days at doses of 50, 100 and 150 mg/kg, acteoside reduced serum uric acid levels by 15.2, 23.8 and 33.1%, respectively, relative to vehicle-treated hyperuricemic mice. Importantly, in non-hyperuricemic mice, the serum uric acid levels were not affected by acetoside treatment. Acteoside also inhibited mouse liver xanthine dehydrogenase XDH and xanthine oxidase XO activity at all three doses. These results suggest that the hypouricemic action of acteoside may be attributable to its inhibition of XDH/XO activity.


2016 ◽  
Vol 3 ◽  
pp. 160-163
Author(s):  
Muhammad Amir Masruhim ◽  
Wisnu Cahyo Prabowo ◽  
Dita Paramitha

Hyperuricemia is a condition in which increased levels of uric acid in the blood. Xanthine oxidase role in the oxidation of hypoxanthine and xanthine to uric acid. One treatment of hyperuricemia is inhibiting xanthine oxidase in the process of formation of uric acid. The purpose of this study to determine the inhibitory activity of xanthine oxidase in the ethanol extract of black betel leaf (Piper sp). Xanthine oxidase inhibitory activity test using UV-Vis spectrophotometry in vitro with a concentration of 5 ppm, 10 ppm and 20 ppm. The data obtained were analyzed using one-way ANOVA. The result is the ethanol extract of black betel leaf has a different activity significantly and IC50 values obtained is 65.96 ppm.


2008 ◽  
Vol 11 (14) ◽  
pp. 1779-1784 ◽  
Author(s):  
Fatemeh Haidari ◽  
Mohammad Reza Rashidi ◽  
Seid Ali Keshavarz ◽  
Soltan Ali Mahboob ◽  
Mohammad Reza Eshraghian ◽  
...  

1991 ◽  
Vol 260 (2) ◽  
pp. H563-H568 ◽  
Author(s):  
A. L. Betz ◽  
J. Randall ◽  
D. Martz

Xanthine oxidase (XO) has been proposed as an important source of free radicals during ischemia. This enzyme normally exists as a dehydrogenase (XD), but it is converted to XO in some ischemic tissues. Recently, treatment of animals with the XD and XO inhibitor allopurinol or with free radical scavengers before cerebral ischemia has been shown to reduce brain injury. Therefore, we studied conversion of XD to XO in three ischemic and nonischemic brain regions during focal cerebral ischemia resulting from permanent occlusion of the middle cerebral artery (MCAO) in anesthetized rats. In nonischemic brain, 16-22% of the enzyme was in the XO form. After 24 h of ischemia this value was not significantly different (10-15%). Neither the total activity of XO nor that of XD changed, indicating that there was no irreversible conversion of XD to XO. To further explore the possible role of XO, we examined the effect of various doses of allopurinol (5, 20, or 100 mg/kg given 1 h before MCAO or 100 mg/kg given 48, 24, and 1 h before MCAO) on uric acid accumulation, brain edema formation, and cerebral blood flow (CBF) 24 h after MCAO. All but the lowest dose of allopurinol greatly reduced the appearance of uric acid in the ischemic brain; however, only the highest dose of allopurinol had any beneficial effect on brain edema. This reduction in brain edema occurred without a significant improvement in CBF. Thus XO is probably not an important source of free radicals in this model of focal cerebral ischemia.


2020 ◽  
Vol 21 (20) ◽  
pp. 7695
Author(s):  
Yiming Wang ◽  
Weikaixin Kong ◽  
Liang Wang ◽  
Tianyu Zhang ◽  
Boyue Huang ◽  
...  

Hyperuricemia (HUA) is a risk factor for chronic kidney disease (CKD). Serum uric acid (SUA) levels in CKD stage 3–4 patients closely correlate with hyperuricemic nephropathy (HN) morbidity. New uric acid (UA)-lowering strategies are required to prevent CKD. The multiple-purpose connectivity map (CMAP) was used to discover potential molecules against HUA and renal fibrosis. We used HUA and unilateral ureteral occlusion (UUO) model mice to verify renoprotective effects of molecules and explore related mechanisms. In vitro experiments were performed in HepG2 and NRK-52E cells induced by UA. Esculetin was the top scoring compound and lowered serum uric acid (SUA) levels with dual functions on UA excretion. Esculetin exerted these effects by inhibiting expression and activity of xanthine oxidase (XO) in liver, and modulating UA transporters in kidney. The mechanism by which esculetin suppressed XO was related to inhibiting the nuclear translocation of hexokinase 2 (HK2). Esculetin was anti-fibrotic in HUA and UUO mice through inhibiting TGF-β1-activated profibrotic signals. The renoprotection effects of esculetin in HUA mice were associated with lower SUA, alleviation of oxidative stress, and inhibition of fibrosis. Esculetin is a candidate urate-lowering drug with renoprotective activity and the ability to inhibit XO, promote excretion of UA, protect oxidative stress injury, and reduce renal fibrosis.


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