Salvia plebeia Extract Inhibits Xanthine Oxidase Activity In Vitro and Reduces Serum Uric Acid in an Animal Model of Hyperuricemia

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.


2019 ◽  
Vol 15 (5) ◽  
pp. 465-486 ◽  
Author(s):  
Haifang Chen ◽  
Yun Yao ◽  
Yuan Zhan ◽  
Hui Jian ◽  
Yan Li ◽  
...  

Background: Erding granule (EDG) widely used as an agent with the effect of heat-clearing, detoxifying, eliminating dampness, relieving jaundice and upper respiratory tract disease in clinical application, but the systematic chemical information and anti-hyperuricemia effect of EDG was still unclear. Methods: An ultra-high performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC/ESI-Q-TOF-MS/MS) method was utilized to rapidly identify the chemical constituents of EDG. The anti-hyperuricemia effect of EDG was evaluated based on the effect on xanthine oxidase inhibitory activity (in vitro) and lowering uric acid (in vivo). Results: 198 compounds were tentatively separated and identified or characterized within 30 min by UHPLC/ESI-Q-TOF MS/MS. These compounds were categorized as 22 coumarins, 38 flavones, 67 alkaloids, 36 organic acids, 16 sesquiterpenes, 14 lignans and 5 the others constituents. Meanwhile, EDG significantly decreases the serum urate level of hyperuricemic mice induced by potassium oxonate, while EDG did not significantly decrease the serum urate level of hyperuricemic mice induced by hypoxanthine and activity of xanthine oxidase in vitro. Conclusion: The method developed was rapid and sensitive to characterize the chemical constituents of EDG, and provide a systematic view of chemical information for EDG. Furthermore, we first discovered the anti-hyperuricemia effect of EDG and it would further provide the reference for clarifying the mechanism of EDG on lowering uric acid.


Scientifica ◽  
2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Nour Elhouda Daoudi ◽  
Mohamed Bouhrim ◽  
Hayat Ouassou ◽  
Mohamed Bnouham

Background. The gout is a metabolic disease that is associated with a high level of uric acid in the blood. This disease is treated with some medications that aim to reduce serum urate levels. However, the use of various medicines leads to the appearance of some side effects, hence the importance of using other treatments based on natural resources. Objective. This study presents some medical treatments, their side effects, and some plants that are used for gout management in Morocco in the aim to valorize them. Methods. We have been consulting various English publications in PubMed, Web of Science, and ScienceDirect published between 1991 and 2019 using the following keywords “drugs,” “gout,” “Morocco,” “medicinal plants,” “in vitro,” and “in vivo” terms. Then, we have classified the medicines, according to their action mechanisms, and we have cited some species that were reported in Moroccan pharmacopeia as antigout. Results. Three methods of the gout medical management were cited in this work: xanthine oxidase inhibitors, uric acid excretion enhancer, and uricase recombinant. However, it was found that these treatments had various side effects. We have described 23 species, and some of them showed experimentally an antigout effect by blocking the “xanthine oxidase” enzyme. These plants belong to 11 families. Lamiaceae represents the most dominant family with six species followed by Asteraceae with two species. Colchicine isolated from Colchicum autumnale is the most known compound for its efficiency towards gout. Conclusion. This work summarized different treatments particularly medicinal plants that are used in Morocco to treat gout disease by blocking uric acid secretion. However, several studies are needed to valorize these antigout natural sources.


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.


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.


Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3254 ◽  
Author(s):  
Heung Yuk ◽  
Young-Sil Lee ◽  
Hyung Ryu ◽  
Seung-Hyung Kim ◽  
Dong-Seon Kim

Toona sinensis leaf is used as a seasonal vegetable in Korea. A 70% ethanol extract of these leaves exhibited potent xanthine oxidase (XO) inhibition, with a 50% inhibitory concentration (IC50) of 78.4 µM. To investigate the compounds responsible for this effect, bioassay-guided purification led to the isolation of five constituents, identified as quercetin-3-O-rutinoside, quercetin-3-O-β-d-glucopyranoside, 1,2,3,4,6-penta-O-galloyl-β-d-glucopyranose (compound 3), quercetin-3-O-α-l-rhamnopyranoside, and kaempferol-3-O-α-l-rhamnopyranoside. Compound 3 showed the most potent inhibition of XO, with an IC50 of 2.8 µM. This was similar to that of allopurinol (IC50 = 2.3 µM), which is used clinically to treat hyperuricemia. Kinetic analyses found that compound 3 was a reversible noncompetitive XO inhibitor. In vivo, the T. sinensis leaf extract (300 mg/kg), or compound 3 (40 mg/kg), significantly decreased serum uric acid levels in rats with potassium oxonate-induced hyperuricemia. Furthermore, ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry analysis identified a high level of compound 3 in the leaf extract. These findings suggest that T. sinensis leaves could be developed to produce nutraceutical preparations.


2012 ◽  
Vol 40 (05) ◽  
pp. 979-991 ◽  
Author(s):  
Chien-Wei Hou ◽  
Ying-Chung Lee ◽  
Hsiao-Fang Hung ◽  
Hua-Wen Fu ◽  
Kee-Ching Jeng

Hyperuricemia causes gouty arthritis, kidney disease, heart disease, and other diseases. Xanthine oxidase (XOD) and urate transporters play important roles in urate homeostasis. Numerous plants have been identified as XOD inhibitors. Longan seeds are known to contain high levels of polyphenols such as corilagin, gallic acid and ellagic acid. We examined the effect of longan seed extract on XOD inhibition and urate transporters GLUT1 and GLUT9 using both in vitro and in vivo assays. The results showed that dried longan seed extract (LSE) and its active components inhibited XOD dose-dependently in vitro. LSE inhibited uric acid production and XOD activity in normal liver cells (clone-9 cells) and was not cytotoxic under the concentration of 200 μg/ml. For the in vivo study, Sprague-Dawley (SD) rats were given intraperitoneally for thirty minutes with or without allopurinol (a XOD inhibitor, 3.5 mg/kg) or LSE (80 mg/kg) and then injected intraperitioneally with 250 mg/kg of oxonic acid and 300 mg/kg of hypoxanthine intragastrically. LSE was able to reduce serum uric acid level and XOD activity in hyperuricemic rats. However, LSE or allopurinol did not inhibit the liver XOD activities. On the other hand, GLUT1 protein was suppressed in kidney and GLUT9 was induced in liver from experimental rats and LSE or allopurinol decreased GLUT9 but increased GLUT1 protein level in the liver and kidney, respectively. These results confirmed the claimed effect of longan seeds on gout and other complications and suggested that its urate reducing effect might be due to modulation of urate transporters and inhibition of circulating xanthine oxidase.


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