Development of Tremella fuciformis polysaccharide craft beer and its hepatorenal protective effects in hyperuricemic mice

Sonneratia apetala Buch-Ham., an exotic mangrove species with antidiabetic, antibacterial, and antioxidant capacities, mainly distributes in the southeast coastal areas in China. The present work investigated the protective effects of Sonneratia apetala leaves and branches extraction (SAL) on hyperuricemia (HUA) in mice. Potassium oxonate (PO) and hypoxanthine (HX) were used to establish the HUA model by challenge for consecutive 7 days. Results revealed that SAL inhibited the increases in kidney weight and index compared to the vehicle group. Meanwhile, SAL significantly decreased the levels of uric acid (UA), creatinine (CRE), and blood urea nitrogen (BUN) in serum. Additionally, SAL inhibited the activity of xanthine oxidase (XOD) in the liver. SAL ameliorated PO- and HX-induced histopathological changes. Moreover, it regulated oxidative stress markers including malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD) activity, and glutathione (GSH) content. Also, SAL inhibited the increases in renal levels of interleukin-6 (IL-6), interleukin-18 (IL-18), interleukin-1β (IL-1β), tumor necrosis factor (TNF-α), monocyte chemotactic protein 1 (MCP-1), and transforming growth factor-β (TGF-β). SAL remarkably reduced suppressor of cytokine signaling 3 (SOCS3), Janus kinase 2 (JAK2), and subsequent phosphorylation of signal transducer and activator of transcription 3 (STAT3) expression. In addition, SAL inhibited the activation of nuclear factor kappa-B (NF-κB) in the kidney. Furthermore, SAL protected against HUA by regulating renal UA transporters of organic anion transporter (OAT1), urate reabsorption transporter 1 (URAT1), and glucose transporter 9 (GLUT9). These findings suggested that SAL ameliorated HUA by inhibiting the production of uric acid and enhancing renal urate excretion, which are related to oxidative stress and inflammation, and the possible molecular mechanisms include its ability to inhibit the JAK/STAT signaling pathway. Thus, SAL might be developed into a promising agent for HUA treatments.

This study investigated the protective effects of a polyherbal tea (PHT) on intestinal injury in hyperuricemia (HUA) mice and the underlying mechanisms. PHT was orally administered to mice for 49 days, while potassium oxonate and hypoxanthine were administered 7 days after PHT administration and continued for 42 days to cause HUA. Treatment with PHT significantly reduced serum uric acid and blood urea nitrogen levels in HUA mice. It also inhibited liver xanthine oxidase activity and promoted intestinal uric acid excretion through the upregulation of transporters GLUT9 and ABCG2. Intestinal barrier integrity was reinforced, as evidenced by the restoration of the villous structure, reduction in edema, and upregulation of tight junction proteins (occludin, ZO-1) and mucin (MUC2). Moreover, PHT suppressed serum LPS levels and inhibited the NF-κB pathway, leading to a reduction in TNF-α and IL-6 levels in the gut. Gut microbiota analysis revealed PHT reversed dysbiosis, enriching beneficial bacteria like Duncaniella sp. and Heminiphilus faecis. By UPLC-MS analysis, 154 compounds of PHT persisted in the gut, suggesting that these compounds are likely to modulate both intestinal barrier function and gut microbiota. These findings suggest that this PHT may have potential as a functional food for the prevention of hyperuricemia.

This study aimed to explore the main chemical components of Jiangniaosuan Formula (JNSF), the therapeutic effect of JNSF on hyperuricemia (HUA) mice, and the underlying mechanism by which JNSF inhibits renal tubular epithelial cell apoptosis. Ultra Performance Liquid Chromatography-Quadrupole-Time of Flight Mass Spectrometry (UPLC-Q-TOF-MS) was used to analyze the chemical composition of JNSF and its serum metabolites. Network pharmacology was performed to predict the potential target genes and pathways. In vitro and in vivo models were established to verify the lower serum uric acid (SUA) and renal protective effects. UPLC-Q-TOF-MS identified 61 chemical compounds in JNSF and 56 metabolites in serum after oral administration. Network pharmacology suggested that Hypoxia-Inducible Factor 1-Alpha (HIF-1α), Cysteine-dependent Aspartate-specific Protease-3 (Caspase-3) and B-cell Lymphoma 2 (Bcl-2) might be the therapeutic targets of JNSF for the HUA treatment and JNSF may exert the therapeutic effect on uric acid nephropathy (UAN) through regulating HIF-1α signaling pathway and apoptosis pathway. In vivo experiments showed that JNSF could reduce SUA, protect renal function and tubular function, alleviate renal interstitial edema and fibrosis, reduce the expression of Reactive Oxygen Species (ROS), HIF-1α and Enhancer of Zeste Homolog 2 (EZH2), and inhibit cell apoptosis in HUA mice. In vitro experiments demonstrated that JNSF reversed apoptosis induced by EZH2 overexpression plasmid. Furthermore, we found that UA could promote the binding of HIF-1α to EZH2 protein and its promoter, enhancing EZH2 transcription, suggesting that JNSF could alleviate the progression of HUA-induced kidney injury by inhibiting the activation of ROS/HIF-1α/EZH2 pathway. JNSF may attenuate HUA-induced renal injury by inhibiting apoptosis through the downregulation of ROS/HIF-1α/EZH2 pathway.

Amelioration effects of α-viniferin on hyperuricemia and hyperuricemia-induced kidney injury in mice

The anti-hyperuricemic effect of epigallocatechin-3-gallate (EGCG) on hyperuricemic mice

Design, synthesis and biological evaluation of novel quinolinone derivatives as potential hypoglycemic agents with hepatorenal protective effects.

Context: Tea (Camellia sinensis (L.) Kuntze [Theaceae]) is used to induce urination and inducing nervous excitation. Green and black teas have multifarious physiological functions. The different effects of green and black tea aqueous extracts (GTEs and BTEs) on hyperuricemia are not definitely reported. Objective: The different effects of GTEs and BTEs on lowering serum uric acid (UA) in hyperuricemic mice were determined. Materials and methods: Kunming mice were divided into nine groups (n = 6/each group). GTEs and BTEs at the doses of 0.5, 1 and 2 g/kg were orally administrated to mice for seven days, respectively. Hepatic xanthine oxidase (XOD) and adenosine deaminase (ADA) activities as mechanisms of actions were assessed. Results: Research indicated that the LD50 of tea extract is greater than 2 g/kg in mice. UA levels were suppressed significantly with dose-dependent treatment of 0.5, 1 and 2 g/kg BTEs (up to 25.5%, 28.7% and 29.8%, respectively); the serum UA levels were decreased by GTEs but not significant. The activities of XOD and ADA in high dose (2 g/kg) groups of both GTEs and BTEs were notably lower than those of the model group. Discussion and conclusions: The results suggested that both GTEs and BTEs have hypouricaemic and renal protective effects on hyperuricemic mice and the latter one was better. Our study sheds light on the research and development of anti-hyperuricemic functional foods and drugs from tea.

Protective effects of cortex fraxini coumarines against oxonate-induced hyperuricemia and renal dysfunction in mice

Purpose: To evaluate the in-vitro inhibition of xanthine oxidase (purified from bovine milk) by extracts of Lycium arabicum, as well as it is in vivo hypouricemic and renal protective effects.Methods: Four extracts of Lycium arabicum, methanol (CrE), chloroform (ChE), ethyl acetate (EaE) and aqueous (AqE) extracts, were screened for their total phenolics and potential inhibitory effects on purified bovine milk xanthine oxidase (XO) activity by measuring the formation of uric acid or superoxide radical. The mode of inhibition was investigated and compared with the standard drugs, allopurinol, quercitin and catechin. To evaluate their hypouricemic effect, the extracts were administered to potassium oxonate-induced hyperuricemic mice at a dose of 50 mg/kg body weight.Results: The results showed that EaE had the highest content of phenolic compounds and was the most potent inhibitor of uric acid formation (IC50 = 0.017 ± 0.001 mg/mL) and formation of superoxide (IC50 = 0.035 ± 0.001 mg/ml). Lineweaver-Burk analysis showed that CrE and EaE inhibited XO competitively, whereas the inhibitory activities exerted by ChE and AqE were of a mixed type. Intraperetoneal injection of L. arabicum extracts (50 mg/kg) elicited hypouricemic actions in hyperuricemic mice. Hyperuricemic mice presented a serum uric acid concentration of 4.71 ± 0.29 mg/L but this was reduced to 1.78 ± 0.11 mg/L by EaE, which was the most potent hyporuricemic extract.Conclusion: L. arabicum fractions have a strong inhibitory effect on xanthine oxidase and and also have a significantly lowering effect on serum and liver creatinine and urea levels in hyperuricemic mice.Keywords: Lycium arabicum, Uric acid, Creatinine, Superoxide, Phenolic compounds, Flavonoids, Hyperuricemia

Antioxidant Activity and Protective Effect of Carob Honey in CCl4-induced Kidney and Liver Injury

Author response for "The hypouricemic and renal protective effects of the Chinese functional tea Ligustrum robustum on hyperuricemic mice"

Extract of Clematis hexapetala regulates uric acid metabolism, alleviates renal inflammation and fibrosis via the PI3K/AKT/NF-κB signaling pathway, and improves hyperuricemia in mice.

Decision letter for "The hypouricemic and renal protective effects of the Chinese functional tea Ligustrum robustum on hyperuricemic mice"

Objectives: Gouty arthritis is caused by the deposition of monosodium urate (MSU) crystals in joints, which is associated with the rise of serum urate content. This study aims to investigate the therapeutic effect of Madecassoside on gouty arthritis and hyperuricemia. Methods: DBA/1 mice were intradermally injected with MSU to stimulate joint inflammation or intraperitoneally injected with MSU to trigger peritonitis. Moreover, ICR mice were exposed to potassium oxonate to stimulate hyperuricemia. Results: Madecassoside repressed MSU-triggered pad swelling, joint 99mTc uptake, and joint inflammation in DBA/1 mice with gouty arthritis. Neutrophil infiltration and IL-1β & IL-6 & MCP-1 secretion was also alleviated in lavage fluids from DBA/1 mice with peritonitis due to Madecassoside treatment. Furthermore, Madecassoside decreased MSU-induced neutrophil cytosolic factor 1, caspase-1 and NLRP3 expression in mice with peritoneal inflammation. In hyperuricemic mice, Madecassoside improved renal dysfunction. Serum uric acid, BUN, and creatinine were down-regulated by Madecassoside. Conclusion: These findings indicate that Madecassoside has potential to ameliorate inflammation in both acute gouty arthritis model and peritonitis model, probably via regulating IL-1β and NLRP3 expression. Practical point: Madecassoside also exhibited a urate-lowering effect and a renal protective effect in hyperuricemic mice.

Review for "The hypouricemic and renal protective effects of the Chinese functional tea Ligustrum robustum on hyperuricemic mice"