Search

Phellinus igniarius is an important medicinal and edible fungus with diverse biological activities. This study aimed to investigate the effects of aqueous extract from P. igniarius (API) on the treatment of hyperuricemia (HUA) and related kidney damage. The chemical constituents of API were determined. The therapeutic effects of API on HUA and renal injury were assessed in adenine/potassium oxonate (PO)-treated mice. The constituent analysis of API revealed a predominance of polysaccharides (33.4 %), followed by total flavonoids (9.1 %), and total triterpenoids (3.5 %). Compared to control, the adenine/PO treatment greatly elevated serum uric acid (UA) levels but this elevation was attenuated by API. In the liver, the expression and activity of xanthine oxidase (XOD) were increased by HUA which were diminished by API. Furthermore, API was found to enhance the expression of UA transporter ABCG2 in the kidney and intestine of HUA mice, suggesting elevating UA excretion. Additionally, API ameliorated HUA-induced renal injury, as indicated by reduced serum BUN/creatinine levels, decreased glomerular and tubular damage, and lowered fibrotic levels. Network pharmacology analysis predicted that P. igniarius may regulate mitochondrial function to improve HUA-related renal injury. This prediction was then substantialized by the API-induced upregulation of NAD+/NADH ratio, ATP level, SOD2 activity, and expression of SOD2/PCG-1α/PPARγ in the kidney of HUA mice. Our results demonstrate that API may effectively ameliorate HUA by reducing UA production in the liver and enhancing UA excretion in the kidney and intestine, and it might be a potential therapy to HUA-related renal injury., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Masson SAS.)

Hyperuricemia (HUA) is a metabolic disease characterized by the increase of serum uric acid (UA) level. Sargentodoxae Caulis (SC) is a commonly used herbal medicine for the treatment of gouty arthritis, traumatic swelling, and rheumatic arthritis in clinic. In this study, a total of fifteen compounds were identified in SC water extract using UHPLC-Q-TOF-MS/MS, including three phenolic acids, seven phenolic glycosides, four organic acids, and one lignan. Then, to study the hypouricemia effect of SC, a HUA mouse model was induced using a combination of PO, HX, and 20% yeast feed. After 14 days of treatment with the SC water extract, the levels of serum UA, creatinine (CRE), blood urea nitrogen (BUN) were reduced significantly, and the organ indexes were restored, the xanthine oxidase (XOD) activity were inhibited as well. Meanwhile, SC water extract could ameliorate the pathological status of kidneys and intestine of HUA mice. Additionally, quantitative real-time PCR (qRT-PCR) and western blotting results showed that SC water extract could increase the expression of ATP binding cassette subfamily G member 2 (ABCG2), organic cation transporter 1 (OCT1), organic anion transporter 1 (OAT1) and organic anion transporter 3 (OAT3), whereas decrease the expression of glucose transporter 9 (GLUT9). This study provided a data support for the clinical application of SC in the treatment of HUA., Competing Interests: Declaration of competing interest The authors declare that the research was conducted without any commercial or financial relationship that might be interpreted as a potential conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

This study was designed to investigate the effects and underlying mechanisms of Astaxanthin (AST) on high-fructose-induced hyperuricemia (HUA) from the perspectives of the uric acid (UA) synthesis and excretion in rat models. Following six weeks of a 10% fructose diet, the level of serum UA effectively decreased in the AST groups as compared to the model group. The enzymatic activities of xanthine oxidase (XOD) and adenosine deaminase (ADA) were significantly inhibited, and the mRNA expression levels of XOD and ADA significantly decreased after the AST administration. These results suggested that the AST reduced UA synthesis by inhibiting the mRNA expressions and enzyme activities of XOD and ADA, thereby contributing to HUA improvement. On the hand, the relative expressions of the mRNA and protein of kidney reabsorption transport proteins (GLUT9 and URAT1) were significantly down-regulated by AST, while that of the kidney secretion proteins (OAT1, OAT3 and ABCG2) were significantly up-regulated by AST. These results indicated that the AST promoted UA excretion by regulating the urate transport proteins, and thus alleviated HUA. This study suggested that the AST could serve as an effective alternative to traditional medicinal drugs for the prevention of fructose-induced HUA.

Chrysanthemum indicum Linne flower (CF) and Cinnamomum cassia (L.) J. Presl bark (CB) extracts have been used as the main ingredients in several prescriptions to treat the hyperuricemia and gout in traditional medicine. In the present study, we investigated the antihyperuricemic effects of DKB114, a CF, and CB mixture, and the underlying mechanisms in vitro and in vivo. DKB114 markedly reduced serum uric acid levels in normal rats and rats with PO-induced hyperuricemia, while increasing renal uric acid excretion. Furthermore, it inhibited the activity of xanthine oxidase (XOD) in vitro and in the liver in addition to reducing hepatic uric acid production. DKB114 decreased cellular uric acid uptake in oocytes and HEK293 cells expressing human urate transporter (hURAT)1 and decreased the protein expression levels of urate transporters, URAT1, and glucose transporter, GLUT9, associated with the reabsorption of uric acid in the kidney. DKB114 exerts antihyperuricemic effects and uricosuric effects, which are accompanied, partially, by a reduction in the production of uric acid and promotion of uric acid excretion via the inhibition of XOD activity and reabsorption of uric acid. Therefore, it may have potential as a treatment for hyperuricemia and gout.

Hyperuricemia represents a risk factor for the progression of chronic kidney disease. Oxidative stress and inflammation are implicated in the mechanisms underlying hyperuricemia-mediated kidney injury. Monolluma quadrangula possesses several beneficial effects; however, its effect on hyperuricemia has not been investigated. This study evaluated the renoprotective and xanthine oxidase (XO) inhibitory activity of M. quadrangula in hyperuricemic rats. Phytochemical investigation revealed the presence of six known flavonoid isolated for the first time from this species. The rats received M. quadrangula extract (MQE) and potassium oxonate (PO) for 7 days. In vitro assays showed the radical scavenging and XO inhibitory activities of MQE, and in silico molecular docking revealed the inhibitory activity of the isolated flavonoids towards XO. Hyperuricemic rats showed elevated serum uric acid, creatinine, urea, and XO activity, and renal pro-inflammatory cytokines, MDA and NO, and decreased GSH, SOD, and catalase. MQE ameliorated serum uric acid, urea, creatinine, and XO activity, and renal pro-inflammatory cytokines. In addition, MQE attenuated renal oxidative stress, enhanced antioxidants, downregulated URAT-1, and GLUT-9 and upregulated OAT-1 in PO-induced rats. In conclusion, M. quadrangula attenuated hyperuricemia and kidney impairment by suppressing XO activity, oxidative stress and inflammation, and modulating urate transporters. [ABSTRACT FROM AUTHOR]

Hyperuricemia is a metabolic disease caused by excessive production of uric acid (UA), which can cause gout, hypertension, hyperlipidemia and other diseases. This study aimed to explore the effect of genistein on hyperuricemia and renal protection in hyperuricemic mice induced by potassium oxonate. Furthermore, genistein significantly downregulated the xanthine oxidase (XOD), adenosine deaminase levels, renal gene expressions of glucose transporter type 9 (mGLUT9) and uric acid transporter 1 (mURAT1) and upregulated organic anion transporters (mOAT1 and mOAT3) and organic cation transporters (mOCT1 and mOCT2). Additionally, genistein improved renal function, renal histopathological features and antioxidant activities in hyperuricemic mice. Genistein also attenuated renal fibrosis by suppressing the JAK2/STAT3 and Wnt/β-catenin signalling pathways in hyperuricemic mice. Overall, this study suggested that both doses of genistein have strong potential against hyperuricemia and associated disorders and may be used as natural supplements for the treatment of UA-related disorders. [ABSTRACT FROM AUTHOR]

It is known that sunflower (Helianthus annuus L.) calathide enzymatically hydrolyzed extract (SCHE) contributes to the regulation of serum uric acid (UA); however, evidence regarding its bioactive components and mechanism are lacking. We identified two water-soluble components (scopoletin and chlorogenic acid) that are abundant in sunflower calathide, especially evaluated for the inhibition of xanthine oxidase (XO) and the expression levels of urate transporters with SCHE. Molecular docking of a chlorogenic acid–XO complex was more stable than that of the Scopoletin–XO, and its binding pockets, which closed the Mo = S center, was similar to xanthine pockets. Moreover, chlorogenic acid exhibited stronger inhibition than that of the scopoletin below 260 μ M , despite the IC50 of scopoletin (577.7 μ M ) being lower than that chlorogenic acid (844.7 μ M ) on the UA generation assessed by a spectrophotometer in vitro. It revealed that chlorogenic acid and scopoletin were competitive inhibitors of XO. In addition, the SCHE (300 μ g/mL) and chlorogenic acid (0.75 mM) obviously inhibited urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) expression levels, while scopoletin significantly upregulated the expression of GLUT9. To summarize, chlorogenic acid served a crucial role in UA regulation consistent with the SCHE and functioned as an important ingredient of SCHE. The strategic analysis of SCHE combined with scopoletin and chlorogenic acid may contribute to the development of food supplemental alternatives on UA metabolism and the reduction of agricultural byproduct waste. [ABSTRACT FROM AUTHOR]

Hyperuricemia (HUA) is caused by increased synthesis and/or insufficient excretion of uric acid (UA). Long-lasting HUA may lead to a number of diseases including gout and kidney injury. Harpagoside (Harp) is a bioactive compound with potent anti-inflammatory activity from the roots of Scrophularia ningpoensis. Nevertheless, its potential effect on HUA was not reported. The anti-HUA and nephroprotective effects of Harp on HUA mice were assessed by biochemical and histological analysis. The proteins responsible for UA production and transportation were investigated to figure out its anti-HUA mechanism, while proteins related to NF-κB/NLRP3 pathway were evaluated to reveal its nephroprotective mechanism. The safety was evaluated by testing its effect on body weight and organ coefficients. The results showed that Harp significantly reduced the SUA level and protected the kidney against HUA-induced injury but had no negative effect on safety. Mechanistically, Harp significantly reduced UA production by acting as inhibitors of xanthine oxidase (XOD) and adenosine deaminase (ADA) and decreased UA excretion by acting as activators of ABCG2, OAT1 and inhibitors of GLUT9 and URAT1. Moreover, Harp markedly reduced infiltration of inflammatory cells and down-regulated expressions of TNF-α, NF-κB, NLRP3 and IL-1β in the kidney. Harp was a promising anti-HUA agent. [Display omitted] • Harp exhibited remarkable amelioration effects on hyperuricemia and hyperuricemia-induced kidney injury. • Harp reduced uric acid production by acting as a potent XOD and ADA dual inhibitor. • Harp as an effective uricosuric agent to regulate the expressions of urate tansportation-associated proteins to enhance UA excretion. • Harp effectively attenuate UA-induced renal injury by regulating the NF-κB/NLRP3 pathway. [ABSTRACT FROM AUTHOR]

Phellodendri Chinese Cortex has long been used to treat hyperuricemia and gout. Berberine (BBR), its characteristic ingredient, has also been shown to be effective in alleviating monosodium urate crystals-triggered gout inflammation in vitro and in vivo. Dihydroberberine (DHB) is a hydrogenated derivative of BBR that showed improved in vivo efficacy on many metabolic disorders. However, its anti-hyperuricemia effect remains underexplored. In the present work, the hypouricemic and renoprotective effects of DHB on hyperuricemic mice were investigated. The hyperuricemic mice model was induced by intraperitoneal injection of potassium oxonate (PO, 300 mg/kg) combined with intragastric administration of hypoxanthine (HX, 300 mg/kg) for 7 days. Different dosages of DHB (25, 50 mg/kg), BBR (50 mg/kg) or febuxostat (Feb, 5 mg/kg) were orally given to mice 1 h after modeling. The molecular docking results showed that DHB effectively inhibited xanthine oxidase (XOD) by binding with its active site. In vitro, DHB exhibited significant XOD inhibitory activity (IC50 value, 34.37 μM). The in vivo results showed that DHB had obvious hypouricemic and renoprotective effects in hyperuricemic mice. It could not only lower the uric acid and XOD levels in serum, but also suppress the activities of XOD and adenosine deaminase (ADA) in the liver. Furthermore, DHB noticeably down-regulated the renal mRNA and protein expression of XOD. Besides, DHB remarkably and dose-dependently ameliorated renal damage, as evidenced by considerably reducing serum creatinine and blood urea nitrogen (BUN) levels, inflammatory cytokine (TNF-α, IL-1β, IL-6 and IL-18) levels and restoring kidney histological deteriorations. Further mechanistic investigation showed that DHB distinctly down-regulated renal mRNA and protein levels of URAT1, GLUT9, NOD-like receptor 3 (NLRP3), apoptosis-associated speck-like (ASC), caspase-1 and IL-1β. Our study revealed that DHB had outstanding hypouricemic and renoprotective effects via suppressing XOD, URAT1, GLUT9 and NLRP3 inflammasome activation in the kidney.

To develop a more effective and safer treatment for Hyperuricemia (HUA), this research investigated the anti-hyperuricemic mechanism of KGM from the perspectives of uric acid (UA) production and excretion in rat model. After four-week experiment, KGM at 168 mg/kg did best in reducing serum UA level. The mechanism of KGM improving HUA was related to its inhibitory capacity to the activities and mRNA expression of xanthine oxidase (XOD) and adenosine deaminase (ADA) in liver. Meanwhile, KGM could also down-regulate the protein expression of uric acid transporters1 (URAT1) and up-regulate the mRNA and protein expression of urate transporter (UAT), organic anion transporter1 (OAT1) and organic anion transporter3 (OAT3) in kidney. Moreover, KGM could also alleviate the renal dysfunction caused by HUA by mitigating urate deposition, and reducing serum creatinine (Cr) and blood urea nitrogen (BUN) levels. KGM might complement existing therapies to improve HUA.

Objectives: To investigate the antihyperuricemia and nephroprotective effects of Orthosiphon stamineus extracts on hyperuricemia (HUA) mice and explore the potential mechanisms. Methods: Orthosiphon stamineus extracts were extracted using 50% ethanol and enriched using ethyl acetate, and characterised utilising UPLC/ESI‐MS. A potassium oxonate (PO) induced hyperuricemic mouse model was used to evaluate antihyperuricemia and nephroprotective effects of O. stamineus ethyl acetate extracts (OSE). Key findings: Eight constituents from OSE were identified and OSE treatment ameliorated HUA by regulating key indicators of kidney dysfunction and xanthine oxidase, adenosine deaminase activity and urate transporters in hyperuricemic mice. Moreover, in renal histopathology analysis, OSE significantly alleviated kidney injury. Conclusions: These findings demonstrate that OSE has antihyperuricemic and nephroprotective effects on PO‐induced HUA mice and those results indicate that OSE could be a safe and effective agent or functional ingredient for treating HUA. [ABSTRACT FROM AUTHOR]

To investigate the effects of Pu-erh ripened tea on lowering uric acid levels and identify its possible mechanisms, three different doses of the tea, with allopurinol as a positive control, were administered intragastrically to hyperuricemic mice. Hyperuricemia was induced in the mice by oral administration of potassium oxonate for 7 days. Serum levels of uric acid, liver xanthine oxidase (XOD) and adenosine deaminase (ADA) activities, and expression of renal mURAT1, mGLUT9, mOAT1 and mOCT1 protein and mRNA were measured. Pu-erh ripened tea, at all doses, significantly lowered serum uric acid levels. At the high and medium doses, it also markedly inhibited liver XOD and ADA activities. Furthermore, mURAT1 and mGLUT9 expression levels were significantly down-regulated by Pu-erh ripened tea treatment. These results suggested that Pu-erh ripened tea can resist to hyperuricemia, possibly by inhibiting, concurrently, uric acid production and renal urate reabsorption.

Graphical abstract Highlights • KGM inhibits the activities of XOD and ADA in serum and liver. • KGM down-regulates mRNA expression of XOD and ADA in liver. • KGM up-regulates mRNA and protein expression of UAT, OAT1 and OAT3 in kidney. • KGM down-regulates protein expression of URAT1 in kidney. Abstract To develop a more effective and safer treatment for Hyperuricemia (HUA), this research investigated the anti-hyperuricemic mechanism of KGM from the perspectives of uric acid (UA) production and excretion in rat model. After four-week experiment, KGM at 168 mg/kg did best in reducing serum UA level. The mechanism of KGM improving HUA was related to its inhibitory capacity to the activities and mRNA expression of xanthine oxidase (XOD) and adenosine deaminase (ADA) in liver. Meanwhile, KGM could also down-regulate the protein expression of uric acid transporters1 (URAT1) and up-regulate the mRNA and protein expression of urate transporter (UAT), organic anion transporter1 (OAT1) and organic anion transporter3 (OAT3) in kidney. Moreover, KGM could also alleviate the renal dysfunction caused by HUA by mitigating urate deposition, and reducing serum creatinine (Cr) and blood urea nitrogen (BUN) levels. KGM might complement existing therapies to improve HUA. [ABSTRACT FROM AUTHOR]

Hyperuricemia is an important pathological basis of gout and a distinct hazard factor for metabolic syndromes and cardiovascular and chronic renal disease, but lacks safe and effective treatments currently. Paeonia × suffruticosa Andrews leaf effectively reduced serum uric acid in gout patients; however, the material foundation and the mechanism remain unclear. To determine the primary active components and mechanism of P. suffruticosa leaf in hyperuricemic mice. The chemical constituents of P. suffruticosa leaf was identified using high-performance liquid chromatographic analysis. The anti-hyperuricemic activity of P. suffruticosa leaf extract (12.5, 25, 50, 100, and 200 mg/kg) and its components was evaluated in hyperuricemic mice induced by a high purine diet for 14 days. Then, the urate-lowering effects of apigenin 7 -O- glucoside (0.09, 0.18, and 0.36 mg/kg) were assessed in another hyperuricemic mice model built by administrating potassium oxonate and adenine for 4 weeks. The inhibitory effect of apigenin 7 -O- glucoside on uric acid production was elucidated by investigating xanthine oxidase activity in vitro and in serum and the liver and through molecular docking. Immunofluorescence and western blot analyses of the expression of renal urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), organic anion transporters 1 (OAT1), and ATP-binding cassette G member 2 (ABCG2) proteins elucidated how apigenin 7 -O- glucoside promoted uric acid excretion. Six compounds were identified in P. suffruticosa leaf: gallic acid, methyl gallate, oxypaeoniflorin, paeoniflorin, galloylpaeoniflorin, and apigenin 7 -O- glucoside. P. suffruticosa leaf extract significantly attenuated increased serum uric acid, creatinine, and xanthine oxidase activity in hyperuricemic mice. Apigenin 7 -O- glucoside from P. suffruticosa leaf reduced uric acid, creatinine, and malondialdehyde serum levels, increased superoxide dismutase activity, and partially restored the spleen coefficient in hyperuricemic mice. Apigenin 7 -O- glucoside inhibited xanthine oxidase activity in vitro and decreased serum and liver xanthine oxidase activity and liver xanthine oxidase protein expression in hyperuricemic mice. Molecular docking revealed that apigenin 7 -O- glucoside bound to xanthine oxidase. Apigenin 7 -O- glucoside facilitated uric acid excretion by modulating the renal urate transporters URAT1, GLUT9, OAT1, and ABCG2. Apigenin 7 -O- glucoside protected against renal damage and oxidative stress caused by hyperuricemia by reducing serum creatinine, blood urea nitrogen, malondialdehyde, and renal reactive oxygen species levels; increasing serum and renal superoxide dismutase activity; restoring the renal coefficient; and reducing renal pathological injury. Apigenin 7 -O- glucoside is the main urate-lowering active component of P. suffruticosa leaf extract in the hyperuricemic mice. It suppressed liver xanthine oxidase activity to decrease uric acid synthesis and modulated renal urate transporters to stimulate uric acid excretion, alleviating kidney damage caused by hyperuricemia. [Display omitted] [ABSTRACT FROM AUTHOR]

Guluronate oligosaccharides (GOS) is a biologically active natural product derived from brown algae. This study aimed to evaluate the amelioration of hyperuricemia and renal inflammation by GOS and its mechanisms. According to the results, GOS treatment reduced the serum uric acid (UA) and blood urea nitrogen (BUN) levels among hyperuricemic mice by 19.6% and 21.5% (P <0.05), at the same time, serum xanthine oxidase (XOD) and adenosine deaminase (ADA) levels were down-regulated to normal. GOS treatment ameliorated the renal pathologization associated with hyperuricemia and reduced renal IL-1β, IL-12, and IL-18 (P <0.05), suggesting a mitigating effect of GOS on renal damage. In addition, GOS supplementation modulates the mRNA levels of renal and intestinal urate transporters to promote uric acid excretion. GOS reversed the intestinal microbiota of hyperuricemic mice, significantly down-regulating the abundances of pernicious bacteria like Bilophila and Tuzzerella , while up-regulating the beneficial intestinal bacteria including Muribaculum , Lachnospiraceae_UCG_006 , Ruminococcus , Faecalibaculum , and Lachnospiraceae_NK4A136_group. Together, guluronate oligosaccharides can improve hyperuricemia by alleviating hyperuricemia-induced renal damage and reversing intestinal microbiota disorders. These findings provide evidence supporting the further development of guluronate oligosaccharides as a novel functional food ingredient suitable for hyperuricemia. [Display omitted] [ABSTRACT FROM AUTHOR]

To investigate the effects of Pu-erh ripened tea on lowering uric acid levels and identify its possible mechanisms, three different doses of the tea, with allopurinol as a positive control, were administered intragastrically to hyperuricemic mice. Hyperuricemia was induced in the mice by oral administration of potassium oxonate for 7 days. Serum levels of uric acid, liver xanthine oxidase (XOD) and adenosine deaminase (ADA) activities, and expression of renal mURAT1, mGLUT9, mOAT1 and mOCT1 protein and mRNA were measured. Pu-erh ripened tea, at all doses, significantly lowered serum uric acid levels. At the high and medium doses, it also markedly inhibited liver XOD and ADA activities. Furthermore, mURAT1 and mGLUT9 expression levels were significantly down-regulated by Pu-erh ripened tea treatment. These results suggested that Pu-erh ripened tea can resist to hyperuricemia, possibly by inhibiting, concurrently, uric acid production and renal urate reabsorption. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Green tea is a Chinese materia medica with the main functions of “inducing urination and quenching thirst”. Green tea polyphenols (GTP) are generally acknowledged as the main active fraction with multiple pharmacological functions in green tea. However, the effect of GTP on hyperuricemia is not clear till now. Aim of study The present study was carried out to investigate the effect of GTP on serum level of uric acid in potassium oxonate (PO)-induced hyperuricemic mice, and explore the underlying mechanisms from two aspects of production and excretion of uric acid. Materials and methods PO and GTP were intragastricly administered to mice for consecutive 7 days. Serum level of uric acid, and xanthine oxidase (XOD) activity in serum and liver were examined. Simultaneously, expression of XOD protein in liver was analyzed by Western blot assay. Expressions of urate transporters including urate-anion transporter (URAT) 1, organic anion transporter (OAT) 1 and 3 in kidney were analyzed by immunohistochemistry staining method. Results 300 and 600 mg/kg GTP significantly decreased serum level of uric acid of hyperuricemic mice in a dose-dependent manner ( p <0.05 or p <0.01). Besides, 300 and 600 mg/kg GTP markedly reduced XOD activity in serum and liver of hyperuricemic mice (both p <0.01). Furthermore, 300 and 600 mg/kg GTP clearly reduced XOD expression in liver, as well as reduced URAT1 expression and increased OAT1 and OAT3 expressions in kidney of hyperuricemic mice ( p <0.05 or p <0.01). Conclusions These results demonstrated that GTP had the effect of lowering uric acid through decreasing the uric acid production and increasing uric acid excretion. Our study suggested that GTP would be a promising candidate as a novel hypouricaemic agent for further investigation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Phellodendri Chinese Cortex has long been used to treat hyperuricemia and gout. Berberine (BBR), its characteristic ingredient, has also been shown to be effective in alleviating monosodium urate crystals-triggered gout inflammation in vitro and in vivo. Dihydroberberine (DHB) is a hydrogenated derivative of BBR that showed improved in vivo efficacy on many metabolic disorders. However, its anti-hyperuricemia effect remains underexplored. In the present work, the hypouricemic and renoprotective effects of DHB on hyperuricemic mice were investigated. The hyperuricemic mice model was induced by intraperitoneal injection of potassium oxonate (PO, 300 mg/kg) combined with intragastric administration of hypoxanthine (HX, 300 mg/kg) for 7 days. Different dosages of DHB (25, 50 mg/kg), BBR (50 mg/kg) or febuxostat (Feb, 5 mg/kg) were orally given to mice 1 h after modeling. The molecular docking results showed that DHB effectively inhibited xanthine oxidase (XOD) by binding with its active site. In vitro , DHB exhibited significant XOD inhibitory activity (IC50 value, 34.37 μM). The in vivo results showed that DHB had obvious hypouricemic and renoprotective effects in hyperuricemic mice. It could not only lower the uric acid and XOD levels in serum, but also suppress the activities of XOD and adenosine deaminase (ADA) in the liver. Furthermore, DHB noticeably down-regulated the renal mRNA and protein expression of XOD. Besides, DHB remarkably and dose-dependently ameliorated renal damage, as evidenced by considerably reducing serum creatinine and blood urea nitrogen (BUN) levels, inflammatory cytokine (TNF-α, IL-1β, IL-6 and IL-18) levels and restoring kidney histological deteriorations. Further mechanistic investigation showed that DHB distinctly down-regulated renal mRNA and protein levels of URAT1, GLUT9, NOD-like receptor 3 (NLRP3), apoptosis-associated speck-like (ASC), caspase-1 and IL-1β. Our study revealed that DHB had outstanding hypouricemic and renoprotective effects via suppressing XOD, URAT1, GLUT9 and NLRP3 inflammasome activation in the kidney. [ABSTRACT FROM AUTHOR]