Longan Seed Extract Reduces Hyperuricemia via Modulating Urate Transporters and Suppressing Xanthine Oxidase Activity

2012 ◽  
Vol 40 (05) ◽  
pp. 979-991 ◽  
Author(s):  
Chien-Wei Hou ◽  
Ying-Chung Lee ◽  
Hsiao-Fang Hung ◽  
Hua-Wen Fu ◽  
Kee-Ching Jeng
Keyword(s):  
Uric Acid ◽  
Xanthine Oxidase ◽  
Serum Uric Acid Level ◽  
Gouty Arthritis ◽  
Seed Extract ◽  
Sprague Dawley ◽  
Glut1 Protein ◽  
Longan Seed

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.

Bmk9 and Uricase Nanoparticle Complex for the Treatment of Gouty Arthritis and Uric Acid Nephropathy

2021 ◽  
Vol 17 (10) ◽  
pp. 2071-2084
Author(s):  
Tianjiao Han ◽  
Meiying Wang ◽  
Wenchao Li ◽  
Mingxing An ◽  
Hongzheng Fu
Keyword(s):  
Uric Acid ◽  
Drug Loading ◽  
Gouty Arthritis ◽  
The Body ◽  
Key Points ◽  
Uric Acid Nephropathy ◽  
Charged Carrier ◽  
Dual Drug

Uric acid is the final product of purine metabolism, and excessive serum uric acid can cause gouty arthritis and uric acid nephropathy. Therefore, lowering the uric acid level and alleviating inflammation in the body are the key points to treating these diseases. A stable nanosuspension of peptide BmK9 was prepared by the precipitation-ultrasonication method. By combining uricase on the surface of a positively charged carrier, a complex consisting of neutral rod-shaped BmK9 and uricase nanoparticles (Nplex) was formed to achieve the delivery of BmK9 and uricase, respectively. The formulation of Nplex has a diameter of 180 nm and drug loading up to 200%, which releases BmK9 and uricase slowly and steadily in drug release tests in vitro. There was significantly improved pharmacokinetic behavior of the two drugs because Nplex prolonged the half-life and increased tissue accumulation. Histological assessments showed that the dual drug Nplex can reduce the inflammation response in acute gouty arthritis and chronic uric acid nephropathy in vivo. In the macrophage system, there was lower toxicity and increased beneficial effect on inflammation with Nplex than free BmK9 or uricase. Collectively, this novel formulation provides a dual drug delivery system that can treat gouty arthritis and uric acid nephropathy.

scholarly journals Preliminary Phytochemical Analysis, Antioxidant and Anti Gout Potential of Aqueous Seed Extract of Punica granatum - An in vitro Study

2021 ◽  
pp. 21-28
Author(s):  
V. Jayavarsha ◽  
R. Gayathri ◽  
V. Vishnu Priya ◽  
J. Selvaraj ◽  
S. Kavitha
Keyword(s):  
Uric Acid ◽  
Xanthine Oxidase ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
In Vitro Study ◽  
Punica Granatum ◽  
Seed Extract ◽  
P Value ◽  
Phytochemical Analysis

Background: Punica granatum belongs to the family punicaceae. Pomegranate has a reservoir of secondary metabolites which possess free radical scavenging activity. Pomegranate has high antioxidants content, which helps in the delayed progress of atherosclerosis, cancer and ageing. Gout is a chronic metabolic disease. It is caused due to increased deposition of monosodium urate crystals in joints. It is caused due to increased intake of purine rich food. Xanthine oxidase converts hypoxanthine to uric acid. Xanthine oxidase (XO) plays an important role in the regulation of production of uric acid. Many research has been done in the extract to analyse the pharmacological characteristics and its beneficial uses. Pomegranate is widely consumed and used as preventive and therapeutic agents. Aim: The aim of this study is to analyse phytochemical constituents, antioxidant and anti gout activity of aqueous seed extract of Punica granatum. Methods: Aqueous seed extract of Punica granatum was prepared and analysed for its phytochemical, antioxidant and anti gout potential by using statistical methods. Results: Phytochemicals such as flavonoids, alkaloids, terpenoids, steroids were present in aqueous extract of Punica granatum. IC50 of antioxidant activity of aqueous seed extract of Punica granatum was found to be 280µg/ml. The extract also exhibited anti gout potential with an IC50 = 310 µg/ml. P value is < 0.05 so, it is significant. Conclusion: Aqueous seed extract of punica granatum can be used to treat gout and to combat various other disorders and also have antioxidant and phytochemical activity. It will be an alternative for synthetic drugs. Herbal extracts are more preferred for its accessibility, cost effectiveness and less side effects. The combined effects of antioxidant and xanthine oxidase inhibitors will be helpful in hyperuricemia treatment.

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 ◽  
...  
Keyword(s):  
Animal Model ◽  
Enzyme Activity ◽  
Uric Acid ◽  
Xanthine Oxidase ◽  
Serum Uric Acid ◽  
Serum Urate ◽  
Key Enzyme ◽  
Ic50 Values

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.

Regulation of intracellular xanthine oxidase by endothelial-derived nitric oxide

1996 ◽  
Vol 271 (5) ◽  
pp. L869-L874 ◽  
Author(s):  
C. G. Cote ◽  
F. S. Yu ◽  
J. J. Zulueta ◽  
R. J. Vosatka ◽  
P. M. Hassoun
Keyword(s):  
Nitric Oxide ◽  
Xanthine Oxidase ◽  
Fold Increase ◽  
Sprague Dawley ◽  
Male Adult ◽  
Dose Dependent Decrease ◽  
Arginine Supplementation ◽  
Hypoxia Reoxygenation

We have previously shown that nitric oxide (NO) donors, such as nitrosoglutathione, inhibit endothelial cell (EC) xanthine dehydrogenase (XD)/xanthine oxidase (XO) activity. The purpose of this study was to assess whether endothelial-derived NO plays any role in the regulation of intracellular XD/XO. We exposed rat pulmonary microvascular EC to L-arginine (precursor of NO) or inhibitors of nitric oxide synthase (NOS), i.e., NG-nitro-L-arginine methyl esther (L-NAME) and NG-nitro-L-arginine, in conditions of normoxia, hypoxia, and hypoxia followed by reoxygenation. Hypoxia alone caused a 1.9- and a 6.6-fold increase in XO and a 5-fold increase in XO + XD activities after 24 and 48 h of exposure, respectively. The combination of hypoxia and L-NAME (300 microM) treatment amounted at 48 h to a 10- and 7.5-fold increase in XO and XO + XD activities, respectively, compared with normoxic untreated cells. L-NAME also prevented the decline in XD/XO activity that occurred in untreated EC after hypoxia-reoxygenation. On the other hand, treatment with L-arginine caused a dose-dependent decrease in XD/XO activity in hypoxic EC compared with cells provided with L-arginine-free medium. In separate experiments, we assessed the role of L-arginine supplementation on the in vivo regulation of lung XD/XO by exposing male adult Sprague-Dawley rats for a period of 5 days to a hypoxic hypobaric atmosphere (0.5 atm). Exposure to hypoxia produced a significant increase in lung tissue XO activity and an increase in the ratio of XO to XD. L-Arginine supplementation in the drinking water prevented the increase in lung XO and the XO-to-XD ratio in hypoxic rats and caused a significant decrease in XO and XD in rats exposed to normoxia. In conclusion, this study suggests that endogenous NO has a significant role in the regulation of XD/XO both in vitro and in vivo. By inhibiting XD/XO activity, NO may have a modulating effect in conditions of hypoxia and hypoxia-reoxygenation, where this enzyme is thought to be important.

Hypouricemic effects of Mesona procumbens Hemsl. through modulating xanthine oxidase activity in vitro and in vivo

2016 ◽  
Vol 7 (10) ◽  
pp. 4239-4246 ◽  
Author(s):  
Jhih-Jia Jhang ◽  
Jia-Wei Ong ◽  
Chi-Cheng Lu ◽  
Chin-Lin Hsu ◽  
Jia-Hong Lin ◽  
...  
Keyword(s):  
Uric Acid ◽  
Xanthine Oxidase ◽  
Serum Uric Acid ◽  
Oxidase Activity ◽  
Xanthine Oxidase Activity

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.

Application of UHPLC/ESI-Q-TOF-MS/MS to Identify Constituents of Erding Granule and Anti-hyperuricemia Effect

2019 ◽  
Vol 15 (5) ◽  
pp. 465-486 ◽  
Author(s):  
Haifang Chen ◽  
Yun Yao ◽  
Yuan Zhan ◽  
Hui Jian ◽  
Yan Li ◽  
...  
Keyword(s):  
Uric Acid ◽  
Xanthine Oxidase ◽  
Chemical Constituents ◽  
Serum Urate ◽  
Chemical Information ◽  
Upper Respiratory Tract ◽  
Serum Urate Level ◽  
Tof Ms

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.

scholarly journals Medicinal Plants as a Drug Alternative Source for the Antigout Therapy in Morocco

Scientifica ◽  
2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Nour Elhouda Daoudi ◽  
Mohamed Bouhrim ◽  
Hayat Ouassou ◽  
Mohamed Bnouham
Keyword(s):  
Uric Acid ◽  
Side Effects ◽  
Medicinal Plants ◽  
Xanthine Oxidase ◽  
Serum Urate ◽  
Alternative Source ◽  
Xanthine Oxidase Inhibitors ◽  
High Level

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.

scholarly journals CONSTITUENT AND ANTIHYPERURICEMIC ACTIVITY OF STELECHOCARPUS BURAHOL LEAVES SUBFRACTIONS

2017 ◽  
Vol 10 (4) ◽  
pp. 435
Author(s):  
Titik Sunarni ◽  
Irda Fidrianny ◽  
Maria Immaculata Iwo ◽  
Komar Ruslan Wirasutisna
Keyword(s):  
Uric Acid ◽  
Ethyl Acetate ◽  
Serum Uric Acid ◽  
Uric Acid Level ◽  
Acid Level ◽  
Serum Uric Acid Level ◽  
Ethyl Acetate Fraction ◽  
Chemical Constituent

Objectives: The goal of this research was to evaluate antihyperuricemic activity of Stelechocarpus burahol leaves subfractions and isolate its chemical constituent of active subfraction.Methods: Ethyl acetate fraction from S. burahol extract was subfractionated by vacuum liquid chromatography and the active subfractions were further subfractionated by classic column chromatography using isocratic eluent followed by isolated the chemical constituent from active subfraction. Hyperuricemic rat model was induced by given  potassium oxonate  intraperitoneally. The inhibitory effect of subfractions on the xanthine oxidase (XO) activity was determined using UV-visible spectrophotometry method.Results: Subfraction E.3, E.4 and E.5 significantly (p<0.05) reduced the serum uric acid level 43, 46 and 33,9%, respectively. The E.3, E.4 and E.5 have very weak activity. Subfraction E.3.2 and E.4.3 significantly (p<0.05) reduced the serum uric acid level 29 and 38 % respectively, however still very weak effect on XO activity.  Chemical constituent which was isolated from E.4.3 subfraction was kaempferol-3-O-rhamnoside.Conclusion: The subfractions of ethyl acetate fraction had antihyperuricemic activity in vivo but less  effect on XO acitivity in vitro. Compound R in active antihyperuricemic of subfraction E.4.3 was kaempferol-3-O-rhamnosideKeyword: Stelechocarpus burahol, subfraction, antihyperuricemic, xanthin oxidase inhibitory activity, kaempferol-3-O-rhamnoside.  

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