potassium-oxonate and Edema

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

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 danger hypothesis proposes that the immune system responds not only to foreign antigens but also to damaged cells or tissues. Recently, uric acid crystals (monosodium urate, MSU) from necrotic cell lysates were identified as a danger signal for dendritic cells (DCs). Our aim was to determine whether MSU modulates immune responses in the skin.. We analyzed the effect of MSU on trinitrochlorobenzene-induced contact hypersensitivity responses using BALB/c mice administered potassium oxonate, an uricase inhibitor, to prevent MSU degradation. Ear swelling response after elicitation and activation profiles of DCs and T cells in draining lymph nodes after sensitization were assessed.. Intradermal administration of MSU augmented the ear swelling response in potassium oxonate-administered mice and enhanced expression of CD86 and CD40 molecules on DCs in the lymph nodes. Activation of DCs was followed by an increase in CD69+ and CD44+ T cells in CD4+ and/or CD8+ subsets in the lymph nodes 4 days after trinitrochlorobenzene sensitization.. These observations demonstrate that MSU is an endogenous danger signal, which augments the contact hypersensitivity response in mice. MSU released from damaged skin may act as an endogenous adjuvant to augment immune response.

Topics: Animals; B7-2 Antigen; CD40 Antigens; Chlorobenzenes; Dendritic Cells; Dermatitis, Contact; Drug Synergism; Ear, External; Edema; Immunity, Cellular; Injections, Subcutaneous; Lymph Nodes; Male; Mice; Mice, Inbred BALB C; Oxonic Acid; Signal Transduction; T-Lymphocyte Subsets; Uric Acid