Administration Of Potassium Oxonate Research Articles

Notopterol Ameliorates Hyperuricemia-Induced Cardiac Dysfunction in Mice

Notopterol is a naturally occurring furanocoumarin compound found in the root of Notopterygium incisum. Hyperuricemia involves the activation of chronic inflammation and leads to cardiac damage. Whether notopterol has cardioprotective potential in hyperuricemia mice remains elusive. The hyperuricemic mouse model was constructed by administration of potassium oxonate and adenine every other day for six weeks. Notopterol (20 mg/kg) and allopurinol (10 mg/kg) were given daily as treatment, respectively. The results showed that hyperuricemia dampened heart function and reduced exercise capacity. Notopterol treatment improved exercise capacity and alleviated cardiac dysfunction in hyperuricemic mice. P2X7R and pyroptosis signals were activated both in hyperuricemic mice and in uric acid-stimulated H9c2 cells. Additionally, it was verified that inhibition of P2X7R alleviated pyroptosis and inflammatory signals in uric acid-treated H9c2 cells. Notopterol administration significantly suppressed expression levels of pyroptosis associated proteins and P2X7R in vivo and in vitro. P2X7R overexpression abolished the inhibition effect of notopterol on pyroptosis. Collectively, our findings suggested that P2X7R played a critical role in uric acid-induced NLRP3 inflammatory signals. Notopterol inhibited pyroptosis via inhibiting the P2X7R/NLRP3 signaling pathway under uric acid stimulation. Notopterol might represent a potential therapeutic strategy against pyroptosis and improve cardiac function in hyperuricemic mice.

The Therapeutic Effect and the Potential Mechanism of Flavonoids and Phenolics of Moringa oleifera Lam. Leaves against Hyperuricemia Mice

The aim of this study is to evaluate the anti-hyperuricemia effect and clarify the possible mechanisms of flavonoids and phenolics of MOL (MOL-FP) in mice. Hyperuricemia mice were generated via intraperitoneal (i.p.) administration of potassium oxonate (PO) and oral gavage (p.o.) of hypoxanthine (HX). Serum uric acid (UA), weight, serum XO activity, hepatic XO activity, urea nitrogen (BUN), creatinine (CRE), serum AST level, serum ALT level, mRNA expression of renal urate-anion transporter 1 (URAT1), glucose transporter 9 (GLUT9), organic anion transporters 1 (OAT1), organic anion transporters 3 (OAT3), and ATP-binding cassette transporter G2 (ABCG2) were determined. The molecular docking was conducted using AutoDock Vina 1.2.0 to screen potential XO inhibitors in MOL-FP. Serum metabolomics was established to collect the metabolic profiles of mice and explore the metabolic changes that occurred after MOL-FP treatment. MOL-FP could notably reduce the serum UA level of hyperuricemia mice by inhibiting XO activity and regulating renal urate transporters. Molecular docking studies indicated that 5-p-coumaroylquinic acid, 3-p-coumaroylquinic acid, and catechin could be potential XO inhibitors. Besides, MOL-FP prevented the pathological process of hyperuricemia by regulating biomarkers associated with purine metabolism, amino acid metabolism, and lipid metabolism.

Naringenin Prevents Inflammation, Apoptosis, and DNA Damage in Potassium Oxonate-Induced Hyperuricemia in Rat Liver Tissue: Roles of Cytochrome C, NF-κB, Caspase-3, and 8-Hydroxydeoxyguanosine.

Background: Hyperuricemia (HU) is a metabolic disease characterized by high uric acid levels in the blood. HU is a risk factor for diabetes, cardiovascular complications, metabolic syndrome, and chronic kidney disease. Purpose: The present study was performed to determine the effect of experimental HU on xanthine oxidase (XO), tumor necrosis factor-alpha (TNF-α), nuclear factor-kappa B (NF-κB), interleukin-17 (IL-17), cytochrome C, glutathione peroxidase (GPx), caspase-3, and 8-hydroxydeoxyguanosine (8-OHdG) levels in liver tissues of rats. Study Design: Thirty-five, male, Wistar albino-type rats were used for this study. Experimental groups were formed as follows: Group 1: control group; Group 2: potassium oxonate (PO) group; group 3: PO+NAR (naringenin; 2 weeks) group; and Group 4: PO (2 weeks)+NAR (2 weeks) group (total of 4 weeks). Methods: The first group was not given anything other than normal rat food and drinking water. In the second group, a 250 mg/kg intraperitoneal dose of PO was administered for 2 weeks. In the third group, 250 mg/kg intraperitoneal PO (application for 2 weeks) and 100 mg/kg NAR intraperitoneally 1 hr after each application were administered. In the fourth group, intraperitoneal PO administration was applied for 2 weeks, followed by intraperitoneal administration of NAR for 2 weeks (4 weeks in total). At the end of the experimental period, XO, TNF-α, NF-κB, IL-17, cytochrome C, GPx, caspase-3, and 8-OHdG levels were determined in liver tissues. Results: HU increased XO, TNF-α, NF-κB, IL-17, cytochrome C, caspase-3, and 8-OHdG levels in liver tissues. However, both 2 and 4 weeks of NAR supplementation decreased these values, and also NAR supplementation led to an increase in GPx levels in tissues. Conclusions: The results of the study show that increased inflammation, apoptosis, and DNA damage in experimental HU can be prevented by administration of NAR due to inhibition of cytochrome C, NF-κB, caspase-3, and 8-OHdG.

Acute oral toxicity assessment and anti-hyperuricemic activity of Alocasia longiloba extracts on Sprague-Dawley rats

Hyperuricemia is defined as a metabolic abnormality that occurs when serum uric acid (UA) level is abnormally high in the body. We previously reported that A. longiloba possesses various important phytochemicals and in vitro xanthine oxidase activity. Despite A. longiloba ethnomedicinal benefits, its toxicity and anti-hyperuricemic effects have not been reported. The present study was carried out to ensure the safety and investigate the anti-hyperuricemic effects of A. longiloba fruit and petiole ethanolic extracts on rats. In the acute toxicity study, extracts were orally administered at a dose of 2000 mg/kg bodyweight and closely monitored for 2-week for any toxicity effects. The rats were then sacrificed and samples were collected and analyzed for hematological, biochemical, and histopathological parameters. The anti-hyperuricemic effect of A. longiloba fruit or petiole extract was investigated through determination of UA levels on potassium oxonate (PO)-induced hyperuricemic rats. Extracts or standard drug treatments were orally administrated 1-h after PO administration for 14-day. Animals were euthanized and samples were collected for further experiments. The toxicity results show, no significant changes were observed in behavioral, bodyweight changes in experimental groups compared to the control. Moreover, there were no significant changes in hematological, biochemical, and histological parameters between extracts treated and control group. In the anti-hyperuricemia study, the fruit and petiole extracts treatments significantly reduced the level of UA in serum compared to the hyperuricemic model group. This study demonstrated that the extracts of A. longiloba have anti-hyperuricemic activity and was found to be non-toxic to rats in acute toxicity test.

ANTIHYPERURICEMIA ACTIVITY OF WUALAE FRUIT (Etlingera elatior Jack R. M. Smith) ETHANOL EXTRACT IN VIVO

Plants Etlingera elatior (Wualae) is a family Zingiberaceae of ​​the genus Etlingera which has a large population in the world. The E. elatior plant is widely used empirically in the community to increase endurance and seasoning in fruit.
 In this study, ethanol extract was used to determine its potential and effectiveness as an antihyperuricemia (in vivo) was tested pharmacologically on Rattus novergicus L. In this study, twenty-four rats were grouped into six groups, namely the ethanol extract of wualae fruit at a dose (100 mg/kgBW, 200 mg/kgBW, 300 mg/kgBW, 400 mg/kgBW), and the negative control group Sodium CMC 0 .5%, and the positive control group used Allopurinol 10 mg/kgBW. Furthermore, To increase the value of uric acid levels, the rats were first induced with 250 mg/kgBW Potassium Oxonate via intraperitoneal (i.p). Furthermore, the preparation according to the treatment was given orally one hour later after the administration of potassium oxonate. At the hour (1, 2, 3), the blood was taken intravenously (i.v) through the rat's tail, and then the uric acid level was analyzed with a photometer. All doses used in this study, namely 100, 200, 300, and 400 mg/kgBW, showed that they could reduce uric acid overall. The effective dose used is the dose (300 mg/kgBW, 400 mg/kgBW). This research can be concluded that the ethanol extract of the fruit of Etlingera elatior (Jack) R.M. Smith (Wualae) has potential as an antihyperuricemia (uric acid) and can be developed as a traditional medicine

ANTIHYPERURICEMIA ACTIVITY OF WUALAE FRUIT (Etlingera elatior Jack R. M. Smith) ETHANOL EXTRACT IN VIVO

Plants Etlingera elatior (Wualae) is a family Zingiberaceae of ​​the genus Etlingera which has a large population in the world. The E. elatior plant is widely used empirically in the community to increase endurance and seasoning in fruit.
 In this study, ethanol extract was used to determine its potential and effectiveness as an antihyperuricemia (in vivo) was tested pharmacologically on Rattus novergicus L. In this study, twenty-four rats were grouped into six groups, namely the ethanol extract of wualae fruit at a dose (100 mg/kgBW, 200 mg/kgBW, 300 mg/kgBW, 400 mg/kgBW), and the negative control group Sodium CMC 0 .5%, and the positive control group used Allopurinol 10 mg/kgBW. Furthermore, To increase the value of uric acid levels, the rats were first induced with 250 mg/kgBW Potassium Oxonate via intraperitoneal (i.p). Furthermore, the preparation according to the treatment was given orally one hour later after the administration of potassium oxonate. At the hour (1, 2, 3), the blood was taken intravenously (i.v) through the rat's tail, and then the uric acid level was analyzed with a photometer. All doses used in this study, namely 100, 200, 300, and 400 mg/kgBW, showed that they could reduce uric acid overall. The effective dose used is the dose (300 mg/kgBW, 400 mg/kgBW). This research can be concluded that the ethanol extract of the fruit of Etlingera elatior (Jack) R.M. Smith (Wualae) has potential as an antihyperuricemia (uric acid) and can be developed as a traditional medicine

Astaxanthin attenuated hyperuricemia and kidney inflammation by inhibiting uric acid synthesis and the NF-κ B/NLRP3 signaling pathways in potassium oxonate and hypoxanthine-induced hyperuricemia mice.

Inflammation is an important pathological feature of hyperuricemia, which in turn aggravates hyperuricemia. Astaxanthin is a carotenoid with strong antioxidant capacity and possesses many biological activities. This study was aimed to evaluate the effect of astaxanthin (ASX) on hyperuricemia and kidney inflammation in potassium oxonate (PO) and hypoxanthine (HX)-induced hyperuricemic mice. Male ICR mice were administered intragastrically with PO and HX (250 mg/kg, respectively) for 14 days. ASX was given by gavage one hour after PO and HX administration. ASX treatment significantly reversed PO and HX-induced hyperuricemia and kidney inflammation in mice as evidenced by decreased serum levels of uric acid (UA), creatinine (Cr), blood urea nitrogen (BUN), and inflammatory factors (IL-1β, IL-6, and TNF-α) and increased activities of antioxidant enzymes (CAT, SOD and GSH-Px). Furthermore, ASX administration effectively inhibited the activities of key enzymes related to UA synthesis (xanthine oxidase (XOD) and adenosine deaminase (ADA)) and modulated the protein expressions of NF-κ B p65, p-NF-κ B p65, Iκ Bα, p-Iκ Bα, NLRP3, ASC, Caspase-1, and cleavedCaspase-1 involved in inflammation pathways. Our results suggested that ASX improved hyperuricemia and kidney inflammation induced by PO and HX, probably by reducing UA synthesis and suppressing the NF-κ B and NLRP3 pathways simultaneously.

Antihyperuricemic, Anti-Inflammatory and Antihypertensive Effect of a Dry Extract from Solidago virgaurea L. (Asteraceae)

Solidago virgaurea L. is a perennial plant used in European traditional medicine as a diuretic or a remedy for inflammatory conditions of the urinary tract but also for gout, especially in the Balkans. The present study was focused on a preclinical, in vivo evaluation of antihyperuricemic, anti-inflammatory, and antihypertensive effects of a dry extract from S. virgaurea L. (ESV). Colorimetric and HPLC–MS techniques were used to identify the main chemical constituents of ESV. Antihyperuricemic effect of ESV was assessed in a rat model of hyperuricemia induced by the administration of potassium oxonate. Antihypertensive effect of ESV was evaluated in hyperuricemic rats by monitoring systolic blood pressure with a non-invasive blood-pressure recording system. The anti-inflammatory effect of ESV was tested using a rat model of paw edema. The main chemical constituents of ESV were rutin and phenolic acids represented by chlorogenic and caffeic acid. ESV demonstrated significant antihyperuricemic effects in rats due to an uricosuric mechanism. Additionally, ESV reduced the progression of arterial hypertension in hyperuricemic rats and also showed anti-inflammatory properties slightly inferior to diclofenac. The results suggest that ESV could be a natural remedy for the treatment of gout and protection against endothelial dysfunction caused by hyperuricemia.

Effectiveness of Gout Therapy with Polyherbal Extract of Shallot (Allium ascalonicum L.) and Red Ginger (Zingiber officinale var rubrum) in Hyperuricemia Mice

Gout can cause inflammation of acute gout arthtritis, as well as other complications. Provision of chemical drugs in the long term have side effects. Shallots (Allium ascalonicum L.) contain flavonoids which can inhibit the xanthine oxidase enzyme, so as to reduce uric acid levels. Red ginger extract (Zingiber officinale var rubrum) is rich in gingerol to reduce uric acid with anti-inflammatory effect. Polyberbal combination is expected to increase the effectiveness of therapy. The research aims to determine the effectiveness of polyherbal combinations. 25 male rats (2-3 months) were divided into five groups, namely negative control, positive control, (P1) 25% red ginger extract: 75% shallot, (P2) 50% red ginger extract: 50% shallot, ( P3) 75% red ginger extract: 25% shallot. Induction of potassium oxonate 250 mg / kg BW intraperitoneally on the 7th day. The first measurement of uric acid on the 14th day with Urid Acid Toos, the 15th to 28th days was administered herbal / chemical drugs according to the group. Measurement of second and third uric acid on days 21 and 28. Data were analyzed by one-way Anova (RAL), further significance tests using Least Significant Different (LSD). The results showed that administration of potassium oxonate and combination of herbal extracts had a significant effect (p <0.05) on uric acid levels in all groups. The most effective herbal combination doses are (P3) 75% red ginger (450 mg / 200 gr) and 25% shallot (150 mg / 200 gr BW). The conclusion of this study is the combination of red ginger extract and shallot can be recommended as a uric acid-lowering agent.

ARISTOLOCHIA BRACTEOLATE RETZ. ATTENUATES HYPERURICEMIA IN A METABOLIC ARTHRITIS RAT MODEL.

Background:The leaves of Aristolochia bracteolata Retz. has been documented in the folk medicine literature for its anti-arthritic activity. The target of the research envisaged was to elucidate the activity of A. bracteolata extract on hyperuricemic condition in arthritis rat model.Materials and Methods:Dried and powdered plant leaves were extracted using ether and chloroform. Potassium oxonate was injected intra-articularly to produce arthritis. The hyperuricemic effect, of A. bracteolate was analyzed by studying levels of uric acid in serum as well as in urine of arthritis induced rats. Effects of plant extracts were also studied on BUN (blood urea nitrogen) levels and fraction of uric acid excreted.Results:Results indicate that administration of A. bracteolata presented substantial change in uric acid concentration, augmented by potassium oxonate administration in rats. The reduction in levels of uric acid levels was nearly same as allopurinol. The investigation also revealed that the primary plant extract has nephroprotective effect by enhancing the production of Prostaglandin E2 and Interleukin-1. Histological studies of rat kidney slices indicated the safety of the present plant extract.Conclusion:The crude extract of A. bracteolate can be used to reduce hyperuricemia in metabolic arthritis produced in rat model, without inducing any potential damaging effects.

Difference in the action mechanism of radon inhalation and radon hot spring water drinking in suppression of hyperuricemia in mice.

Although radon therapy is indicated for hyperuricemia, the underlying mechanisms of action have not yet been elucidated in detail. Therefore, we herein examined the inhibitory effects of radon inhalation and hot spring water drinking on potassium oxonate (PO)–induced hyperuricemia in mice. Mice inhaled radon at a concentration of 2000 Bq/m3 for 24 h or were given hot spring water for 2 weeks. Mice were then administrated PO at a dose of 500 mg/kg. The results obtained showed that serum uric acid levels were significantly increased by the administration of PO. Radon inhalation or hot spring water drinking significantly inhibited elevations in serum uric acid levels through the suppression of xanthine oxidase activity in the liver. Radon inhalation activated anti-oxidative functions in the liver and kidney. These results suggest that radon inhalation inhibits PO-induced hyperuricemia by activating anti-oxidative functions, while hot spring water drinking may suppress PO-induced elevations in serum uric acid levels through the pharmacological effects of the chemical compositions dissolved in it.