potassium-oxonate and Arthritis--Gouty

Pyroptosis has been found implicated in several diseases, however, whether it was involved in gouty arthritis remained unclear. Our study was performed to uncover the role of pyroptosis in gouty arthritis based on a mice model.. Mouse gouty arthritis model was established by injections of potassium oxonate (PO), monosodium urate (MSU) and pyroptosis suppressor disulfiram. The diameter of the ankle joints was measured, and ankle joints morphology was observed with hematoxylin-eosin (H&E) staining. Uric acid, creatinine and blood urea nitrogen (BUN) concentrations were measured, while cytokines level and xanthine oxidase (XOD) activity were quantified. Relative pyroptosis markers expressions were determined using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot as needed.. In mouse model, PO and MSU injections cause damage to right ankle, increase the root thickness ratio and uric acid, creatinine and BUN levels in serum and decrease the uric acid and creatinine levels in urine. Also, under PO and MSU treatment, up-regulated XOD activity, inflammatory cytokines levels and pyroptosis markers expressions are observed. Negative regulation of mice injury by disulfiram treatment is also observed.. Pyroptosis inhibition might alleviate PO- and MSU-induced gouty arthritis, providing possible therapeutic strategies for gouty arthritis.

Topics: Animals; Arthritis, Gouty; Creatinine; Cytokines; Disease Models, Animal; Disulfiram; Humans; Mice; Oxonic Acid; Pyroptosis; Uric Acid

Rhizoma smilacis glabrae (RSG, tufuling) has been widely used in traditional Chinese medicine for deoxidation, dampness relief, and easing joint movement. The chemical composition of RSG has been systematically confirmed, and some of its compounds have been revealed to possess antioxidant, anti-inflammatory, immunomodulatory, hypouricemic, and hepatoprotective effects.. We aimed to clarify whether a RSG extract attenuates hyperuricemia, paw edema, and renal injury in mice with potassium oxonate (PO)- and monosodium urate (MSU)-induced chronic hyperuricemia and gout.. RSG water extract was obtained and analyzed by HPLC-DAD-MS/MS. To establish a murine model with chronic hyperuricemia and gout, PO was orally administered daily from day 0 to day 24, whereas MSU was injected into the tibiotarsal joint on day 21. The mice in the drug intervention groups were treated once daily with doses of allopurinol or RSG extract from day 21 to day 24. The diameter of the ankle joints was measured with calipers. Serum TNF-α and IL-1β concentrations, hepatic XOD activity, and uric acid, creatinine, and blood urea nitrogen (BUN) levels were also determined. The right kidney and articular cavities were fixed, cut into sections, and stained with hematoxylin and eosin.. Nine compounds in the RSG water extract were unambiguously identified as 5-O-caffeoylshikimic acid, neoastilbin, astilbin, taxifolin, neoisoastilbin, isoastilbin, engeletin, isoengeletin, and trans-resveratrol. The RSGE treatment dose-dependently reduced PO- and MSU-induced paw edema, serum TNF-α, IL-1β, IL-6, IL-12, uric acid, and BUN, while significantly elevated serum IL-10, urinary uric acid and creatinine levels as compared with the respective values in the hyperuricemic and gouty mice group (vehicle group). Moreover, the hepatic XOD activity was dose-dependently reduced by the RSGE treatment. In addition, RSGE treatment not only ameliorated the infiltration of inflammatory cells, tubular dilation and vacuole formation in renal tubular, but also improved the synovial hyperplasia, reduced inflammatory cells infiltration into the synovium, and diminished the erosive damage in the cartilage.. The murine model with chronic hyperuricemia and gout be built in present study is consistent with the clinical symptoms of patients with long-standing hyperuricemia and acute gouty arthritis. RSG water extract has potent efficacy in ameliorating murine hyperuricemia and gout induced by PO and MSU.

Topics: Animals; Antioxidants; Arthritis, Gouty; Disease Models, Animal; Drugs, Chinese Herbal; Edema; Flavonols; Glycosides; Gout; Hyperuricemia; Interleukin-1beta; Kidney; Liver; Male; Mice, Inbred BALB C; Oxonic Acid; Phytotherapy; Plant Extracts; Rhizome; Smilax; Tandem Mass Spectrometry; Uric Acid

Topics: Anacardiaceae; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Gouty; Chalcone; Dose-Response Relationship, Drug; Edema; Enzyme Inhibitors; Flavanones; Hyperuricemia; Inflammation; Male; Mice; Mice, Inbred Strains; Molecular Structure; Oxonic Acid; Structure-Activity Relationship; Uric Acid; Xanthine Oxidase

The Gnaphalium affine D. Don is used in China as a folk medicine to treat gout, anti-inflammatory, antitussive and expectorant activities. The aim of this study was to evaluate the potential of the extract of G. affine to treat hyperuricemia and acute gouty arthritis in animal model.. G. affine extract was evaluated in an experimental model with potassium oxonate (PO) induced hyperuricemia in mice which was used to evaluate anti-hyperuricemia activity and xanthine oxidase (XO) inhibition. Therapies for acute gouty arthritis was also investigated on monosodium urate (MSU) crystal induced paw edema model.. G. affine extract showed expressive results on active in reducing serum uric acid (Sur) through effect renal mGLUT9 and mURAT1 mainly and inhibit XO activity in vivo. The extract of G. affine also showed significant anti-inflammatory activity and reduced the paw swelling on MSU crystal-induced paw edema model. Meanwhile, eight major compounds were identified by HPLC-ESI-QTOF-MS/MS.. The extract of G. affine showed significant effect on evaluated models and therefore may be active agents for the treatment of hyperuricemia and acute gouty arthritis.

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Gouty; Chromatography, High Pressure Liquid; Disease Models, Animal; Edema; Gnaphalium; Hyperuricemia; Male; Mice; Mice, Inbred ICR; Oxonic Acid; Plant Extracts; Tandem Mass Spectrometry; Uric Acid; Xanthine Oxidase

Sanmiao formula (SM) is a compound prescription, which has been used in traditional Chinese medicine since the Ming Dynasty for gouty and rheumatoid arthritis treatments. However, no evidence has been unfolded to show the relationship between SM and gouty arthritis (GA), particularly inhibiting cartilage matrix degradation. In the present study, we undertook a characterization of anti-GA activity of SM using an in vivo rat model induced by potassium oxonate and cold bath together with in vitro studies with chondrocytes for further molecular characterization. Potassium oxonate and cold bath rats were treated with SM at doses of 7.2g/kg per day for 5days. SM treatments significantly suppressed the swelling rate and the severe pathologic changes in the joints of the animals in gout model. Inflammatory factors count by ELISA analysis, SM exhibited inhibition on IL-1β and TNF-α. Moreover, histological analysis of the joints and SM-serum substantially interfered with the MSU-induced expression of glycosaminoglycans (GAG), up-regulated the content of proteoglycan. Importantly, SM interfered with GA-augmented expression of matrix metalloproteinases (MMPs) -3 and aggrecanases (ADAMTS)-4, which are considered to be key enzymes in cartilage matrix degradation, and simultaneously augmented GA-reduced tissue inhibitors of metalloproteinases (TIMPs) -1 and -3 expression in the joints and chondrocytes. Therefore, SM is looking forward to be a potential novel agent that could prevent cartilage matrix degradation effectively in gouty arthritis, and this provides a new target for development of new medicines.

Topics: ADAM Proteins; ADAMTS4 Protein; Animals; Arthritis, Gouty; Cells, Cultured; Chondrocytes; Complex Mixtures; Down-Regulation; Drugs, Chinese Herbal; Humans; Hydrolysis; Interleukin-1beta; Joints; Male; Matrilin Proteins; Matrix Metalloproteinase 3; Medicine, Chinese Traditional; Models, Animal; Oxonic Acid; Procollagen N-Endopeptidase; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

Jatropha isabellei Müll Arg. (Euphorbiaceae) is a medicinal plant that has been used in South American folk medicine for the treatment of arthritic diseases, particularly gout.. This study was designed to verify the antinociceptive, anti-inflammatory and hypouricemic potential of Jatropha isabellei.. Rats were orally administered with the crude extract (100-300 mg/kg) or a fraction that is rich in alkaloids (0.15 mg/kg) of Jatropha isabellei. An intra-articular (i.a.) injection of 50 μl of monosodium urate (MSU) crystals (1.25mg/site) was used to generate the gout model to assess the effect of the treatment on nociception (thermal and mechanical hyperalgesia) and inflammation (oedema and neutrophil infiltration). The effect of Jatropha isabellei on the serum levels of uric acid was evaluated in a model of hyperuricaemia induced by the intraperitoneal injection of potassium oxonate (250 mg/kg). The side effects were analysed using an open-field test, gastric lesion assessment and by measuring the levels of the ALT and AST enzymes.. Our study demonstrated that the crude extract of Jatropha isabellei and a fraction rich in alkaloids were able to prevent the thermal hyperalgesia, mechanical allodynia, oedema and neutrophil infiltration induced by intra-articular MSU injection in rats. On the other hand, treatment with Jatropha isabellei did not alter the uric acid levels increased by potassium oxonate in the hyperuricaemia model. In addition, Jatropha isabellei did not induce gastric lesions or liver damage and did not alter spontaneous locomotor activity.. The crude extract of Jatropha isabellei and its fraction rich in alkaloid presents antinociceptive and anti-inflammatory effects in a rat gout model, similar to that observed after treatment with colchicine, supporting the traditional use of this plant in gouty patients.

Topics: Alkaloids; Animals; Anti-Inflammatory Agents; Arthritis, Gouty; Biomarkers, Pharmacological; Disease Models, Animal; Edema; Hyperalgesia; Hyperuricemia; Jatropha; Male; Motor Activity; Neutrophil Infiltration; Oxonic Acid; Peroxidase; Phytotherapy; Plant Extracts; Rats; Stomach Ulcer; Uric Acid; Xanthine Oxidase

The ethanolic extract of Lychnophora trichocarpha Spreng. is used in Brazilian folk medicine to treat bruise, pain and inflammatory diseases.. The present study aimed at investigating whether ethanolic extract of L. trichocarpha, its ethyl acetate fraction and its main bioactive compounds could be useful to treat gouty arthritis by countering hyperuricemia and inflammation.. L. trichocarpha ethanolic extract (LTE), ethyl acetate fraction from ethanolic extract (LTA) and isolated compounds were evaluated for urate-lowering activity and liver xanthine oxidase (XOD) inhibition in oxonate-induced hyperuricemic mice. Anti-inflammatory activity in monosodium urate crystal-induced paw oedema, an experimental model of gouty arthritis, was also investigated.. Crude ethanolic extract and its ethyl acetate fraction showed significant urate-lowering effects. LTE was also able to significantly inhibit liver xantine oxidase (XOD) activity in vivo at the dose of 250mg/kg. Luteolin, apigenin, lupeol, lychnopholide and eremantholide C showed the anti-hyperuricemic activities among tested compounds. Apigenin also showed XOD inhibitory activity in vivo. Luteolin, lychnopholide, lupeol and eremantholide C, in turn, did not shown significant inhibitory activity towards this enzyme, indicating that this mechanism is not likely to be involved in urate-lowering effects of those compounds. LTE, LTA, lupeol, β-sitosterol, lychnopholide, eremantholide, luteolin and apigenin were also found to inhibit monosodium urate crystals-induced paw oedema in mice.. Ethanolic extract of Lychnophora trichocarpha and some of its bioactive compounds may be promising agents for the treatment of gouty arthritis since they possesses both anti-hiperuricemic and anti-inflammatory properties.

Topics: Acetates; Animals; Anti-Inflammatory Agents; Arthritis, Gouty; Asteraceae; Ethanol; Flavonoids; Hyperuricemia; Inflammation; Liver; Male; Mice; Oxonic Acid; Phytotherapy; Plant Components, Aerial; Plant Extracts; Solvents; Uric Acid; Xanthine Oxidase

Lithospermic acid (LSA) was originally isolated from the roots of Salvia mitiorrhiza, a common herb of oriental medicine. Previous studies demonstrated that LSA has antioxidant effects. In this study, we investigated the in vitro xanthine oxidase (XO) inhibitory activity, and in vivo hypouricemic and anti-inflammatory effects of rats. XO activity was detected by measuring the formation of uric acid or superoxide radicals in the xanthine/xanthine oxidase system. The results showed that LSA inhibited the formation of uric acid and superoxide radicals significantly with an IC50 5.2 and 1.08 microg/ml, respectively, and exhibited competitive inhibition. It was also found that LSA scavenged superoxide radicals directly in the system beta-NADH/PMS and inhibited the production of superoxide in human neutrophils stimulated by PMA and fMLP. LSA was also found to have hypouricemic activity on oxonate-pretreated rats in vivo and have anti-inflammatory effects in a model of gouty arthritis. These results suggested that LSA is a competitive inhibitor of XO, able to directly scavenge superoxide and inhibit superoxide production in vitro, and presents hypouricemic and anti-inflammatory actions in vivo.

Topics: Allopurinol; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Gouty; Benzofurans; Depsides; Disease Models, Animal; Dose-Response Relationship, Drug; Enzyme Inhibitors; Humans; Hyperuricemia; Inflammation; Male; Molecular Conformation; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Oxonic Acid; Rats; Rats, Wistar; Reactive Oxygen Species; Tetradecanoylphorbol Acetate; Uric Acid; Xanthine Oxidase