• Development and Reproduction
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• v.24 no.2
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• pp.89-100
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• 2020

Clerodendrum trichotomum is a folk medicine exhibiting anti-hypertension, anti-arthritis, and anti-rheumatism properties. However, little is known about whether the material might prevent hyperuricemia and associated inflammation. In this study, we explored whether C. trichotomum leaf extract (CTE) prevented hyperuricemia induced by potassium oxonate (PO) in mice. CTE (400 mg/kg body weight) significantly reduced the serum uric acid (UA), blood urea nitrogen (BUN), and serum creatinine levels and increased urine UA and creatinine levels. CTE ameliorated PO-induced inflammation and apoptosis by reducing the levels of relevant proteins in kidney tissues. Also, CTE ameliorated both UA-induced inflammatory response in RAW 263.7 cells and UA-induced cytotoxicity in HK-2 cells. In addition, liver transcriptome analysis showed that CTE enriched mainly the genes for mediating positive regulation of MAPK cascade and apoptotic signaling pathways. Together, the results show that CTE effectively prevents hyperuricemia and associated inflammation in PO-induced mice.

• Journal of Life Science
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• v.29 no.1
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• pp.37-44
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• 2019

Leaves of Sasa quelpaertensis Nakai are used in folk medicine for their anti-inflammatory, antipyretic, and diuretic properties. To ensure efficient utilization of S. quelpaertensis leaf, we previously reported a preparation method for phytochemical-rich extract (PRE) using the leaf residue, which was produced after hot water extraction. This study was undertaken to evaluate the hypouricemic potential of S. quelpaertensis leaf PRE in potassium oxonate (PO)-induced hyperuricemic mice. The administration of PRE significantly reduced serum uric acid (UA), blood urea nitrogen (BUN), and serum creatinine levels and increased urine UA and creatinine levels in the PO-induced hyperuricemic mice. It also reduced liver UA levels and xanthine oxidase (XA) activity. A histological analysis revealed that PRE administration protected against PO-induced liver damage, pointing to anti-inflammatory and cytoprotective effects in PO-induced hyperuricemic mice. We analyzed the transcriptome response to PRE administration in PO-induced hyperuricemic mice using RNA sequencing (RNA-Seq) in kidney tissues. The administration of PRE mainly enriched genes involved in mediating immune and inflammatory responses and the metabolic pathway. A Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the metabolic pathway, purine metabolism, and antibody biosynthesis were the major pathways altered in the PRE and PO groups. These results suggest a potential role for PRE in the prevention and treatment of hyperuricemia with inflammation.

• YAKHAK HOEJI
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• v.47 no.5
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• pp.307-310
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• 2003

Ethanol extract of Actinidia polygama Max. (AP) was examined for hypouricemic activity in potassium oxonateinduced hyperuricemic animal model. Ethanol extract of AP lowered the plasma uric acid level by 20％ when compared to the hyperuricemic control group. AP ether fraction at a dose of 100 mg/kg showed 27％ reduction, whose efficacy was comparable to the probenecid-treated group. AP ether fraction-treated group also showed 23％ reduction of urate in urine and this result suggests that AP ether fraction has anti-gout activity probably due to xanthine oxidase inhibition.

• Toxicological Research
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• v.35 no.4
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• pp.371-387
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• 2019

Although the dried root of Saposhnikovia divaricata (Turcz.) Schischk. (Umbelliferae) is a popular medicinal plant in East Asia, there has been no systemic toxicological evaluation of a water extract of Saposhnikoviae Radix (SRE). In this experiment, an oral acute and 13-week subchronic toxicological evaluations of SRE (500-5,000 mg/kg body weight) were performed in both sexes of Crl:CD(SD) rats. Based on the results from mortality, clinical signs, effects on body weight and organ weight, clinical biochemistry, hematology, urinalysis, and histopathology, significant acute, 4-week repeated dose range finding (DRF) and 13-week subchronic toxicity of SRE was not observed in either sex of rats; thus, the no observed adverse effect level (NOAEL) was 5,000 mg (kg/day). To identify anti-hyperuricemia potential of SRE, the suppressive effect of SRE was determined in mice challenged with potassium oxonate (PO; 250 mg/kg) via intraperitoneal injection for 8 days (each group; n = 7). SRE supplementation suppressed the uric acid level in urine through significant xanthine oxidase (XO) inhibitory activity. Kidney dysfunctions were observed in PO-challenged mice as evidenced by an increase in serum creatinine level. Whereas, SRE supplementation suppressed it in a dose-dependent manner. Collectively, SRE was safe up to 5,000 mg (kg/day) based on NOAEL found from acute and 13-week subchronic toxicological evaluations. SRE had anti-hyperuricemia effect and lowered the excessive level of uric acid, a potential factor for gout and kidney failure.

• Mycobiology
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• v.42 no.3
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• pp.296-300
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• 2014

We selected Pleurotus ostreatus from among several edible mushrooms because it has high anti-gout xanthine oxidase (XOD) inhibitory activity. The maximal amount of XOD inhibitor was extracted when the Pleurotus ostreatus fruiting body was treated with distilled water at $40^{\circ}C$ for 48 hr. The XOD inhibitor thus obtained was purified by Sephadex G-50 gel permeation chromatography, ultrafiltration, $C_{18}$ solid phase extraction chromatography and reverse-phase high-performance liquid chromatography with 3% of solid yield, and its XOD inhibitory activity was 0.9 mg/mL of $IC_{50}$. The purified XOD inhibitor was a tripeptide with the amino acid sequence phenylalanine-cysteine-histidine and a molecular weight of 441.3 Da. The XOD inhibitor-containing ultrafiltrates from Pleurotus ostreatus demonstrated dose-dependent anti-gout effects in a Sprague-Dawley rat model of potassium oxonate-induced gout, as shown by decreased serum urated levels at doses of 500 and 1,000 mg/kg, although the effect was not as great as that achieved with the commercial anti-gout agent, allopurinol when administered at a dose of 50 mg/kg.

• Journal of Acupuncture Research
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• v.40 no.1
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• pp.53-60
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• 2023

Background: This study aimed to investigate the effects of Oenanthe javanica (OJ) extracts on rats with potassium oxonate (PO)-induced hyperuricemia. Methods: The effects of OJ extract on rats with PO-induced hyperuricemia-induced were monitored. Changes in the body weight and organ indices of hyperuricemic rats were calculated to detect anti-hyperuricemic effects. Blood samples were collected to observe the effect of reducing serum uric acid concentration. Kidney tissues were stained to observe histopathological changes under a microscope. The activity of xanthine oxidase (XO), which catalyzes xanthine to uric acid in the liver, was assessed to observe the inhibitory effect of XO. Results: 1. The body weight of hyperuricemic rats showed no considerable differences between the control group and the treatment group. The OJ group had significantly improved liver index, whereas the allopurinol group had improved liver and kidney indices. 2. Serum uric acid levels increased significantly after PO injection, and the OJ and allopurinol groups showed a significant reduction effect. 3. PO injection led to the inflammation of kidney tissues, and OJ improved it significantly. 4. The activity of XO after PO injection was significantly increased, and allopurinol significantly inhibited XO activity in the liver. Conclusion: In the hyperuricemia rat model, OJ extract reduced uric acid concentration and demonstrated its anti-inflammatory effects. Thus, OJ extracts can be used to lower uric acid levels.

• Journal of Acupuncture Research
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• v.40 no.2
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• pp.135-142
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• 2023

Background: This study aimed to investigate hyperuricemia, renal inflammation, and xanthine oxidase (XO) activity improvement in a rat model treated with Scutellaria baicalensis extract (SBE). Methods: The rats were divided into 4 groups (n = 5 each), including sham, potassium oxonate (PO) injected hyperuricemia (control group), PO + 10 mg/kg allopurinol administrated (allopurinol group), and a PO + 50 mg/kg SBE administrated (SBE group), to investigate the effectiveness and molecular mechanisms of SBE. The effects of SBE on PO-induced hyperuricemia rats, renal inflammation, and XO activity were measured. Body weight and organ index of the kidney and liver were measured in PO-induced hyperuricemia rats, and serum uric acid level was extracted from whole blood and was measured. Renal inflammation was observed under a microscope after sections. XO activity was measured by liver tissue and serum XO levels. Results: Organ indexes of the kidney and liver in rats were significantly decreased in the allopurinol group than in the control group and with no significant difference in the SBE group. A PO injection for 5 days significantly increased serum uric acid levels in the control group compared to the sham group. Meanwhile, the SBE and allopurinol groups have significantly decreased serum uric acid levels compared to the control group. The SBE group revealed effectively improved renal histopathological changes compared to the control group. The XO inhibitor, allopurinol, significantly decreased XO activity. Additionally, SBE significantly lowered XO activity in rats. Conclusion: SBE can be used as an effective treatment for gout in the future.

• Journal of Ginseng Research
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• v.45 no.5
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• pp.565-574
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• 2021

Background: Saengmaeksan (SMS) is a traditional Korean medicine composed of three herbs, Panax ginseng, Schisandra chinensis, and Liriope platyphylla. SMS is used to treat respiratory and cardiovascular disorders. However, whether SMS exerts antihyperuricemic effects is unknown. Methods: Effects of the SMS extract in water (SMS-W) and 30% ethanol (SMS-E) were studied in a rat model of potassium oxonate-induced hyperuricemia. Uric acid concentrations and xanthine oxidase (XO) activities were evaluated in the serum, urine, and hepatic tissue. Using renal histopathology to assess kidney function and uric acid excretion, we investigated serum creatinine and blood urea nitrogen concentrations, as well as protein levels of renal urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), and organic anion transporter 1 (OAT1). The effects of SMS on in vitro XO activity and uric acid uptake were also evaluated. The components of SMS were identified using Ultra Performance Liquid Chromatography (UPLC). Results: SMS-E reduced serum uric acid and creatinine concentrations, and elevated urine uric acid excretion. SMS-E lowered XO activities in both the serum and liver, and downregulated the expression of renal URAT1 and GLUT9 proteins. SMS-E reduced renal inflammation and IL-1b levels in both the serum and kidneys. SMS-E inhibited both in vitro XO activity and urate uptake in URAT1-expressing oocytes. Using UPLC, 25 ginsenosides were identified, all of which were present in higher levels in SMS-E than in SMS-W. Conclusion: SMS-E exhibited antihyperuricemic effects by regulating XO activity and renal urate transporters, providing the first evidence of its applicability in the treatment of hyperuricemia and gout.

• The Korea Journal of Herbology
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• v.32 no.6
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• pp.23-29
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• 2017

Objective : Hyperuricemia is a metabolic disease characterized by elevated blood uric acid levels, and its prevalence is rapidly increasing worldwide. Alpiniae Oxyphyllae Fructus (AO) belonging to Zingiberaceae is one of well-known traditional medicines in China and Korea, and has been used to treat intestinal disorders, urosis, diuresis, and chronic glomerulonephritis traditionally. However, the effect of AO has not been studied. In this study we investigated the anti-hyperuricemic effect of AO, and the mechanisms underlying the effect in potassium oxonate (PO)-induced hyperuricemic rats. Methods : To examine the anti-hyperuricemic effects of the AO extract, serum uric acid levels were analyzed in normal and PO-induced hyperuricemic rats. The mechanism underlying the effects of the AO extract on uric acid levels was studied through xanthine oxidase (XOD) activity test and uric acid uptake assay in vitro. The chemical finger printing of the AO extract was analyzed using HPLC-DAD. Results : The AO extract significantly reduced serum uric acid levels in normal as well as PO-induced hyperuricemic rats. It also significantly inhibited the uptake of uric acid in oocytyes and human embryonic kidney cells (HEK293) expressing urate transporter (URAT)1, but not XOD activity in vitro. The chemical finger printing analysis of the AO extract showed nootkatone as a main component. Conclusion : The AO extract exhibits anti-hyperuricemic effects, and these effect were accompanied by increasing excretion of uric acid in kidney. Therefore, the AO extract could be used for prevention or treatment of hyperuicemia and gout.