scholarly journals Evaluation of the Antihyperuricemic Activity of Phytochemicals fromDavallia formosanaby Enzyme Assay and Hyperuricemic Mice Model

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Chen-Yu Chen ◽  
Chi-Chang Huang ◽  
Keng-Chang Tsai ◽  
Wei-Jan Huang ◽  
Wen-Ching Huang ◽  
...  
Keyword(s):  
Uric Acid ◽  
Enzyme Assay ◽  
Critical Factor ◽  
Serum Urate ◽  
Flavonoid Glycosides ◽  
Mice Model ◽  
Inhibitory Activities ◽  
Potassium Oxonate

Abnormal serum urate levels are recognized as a critical factor in the progression of several chronic diseases. To evaluate the antihyperuricemic effect ofDavallia formosana, the inhibitory activities of 15 isolated phytochemicals, including five novel compounds of 6,8-dihydroxychromone-7-C-β-d-glucopyranoside (1), 6,8,3′,4′-tetrahydroxyflavanone-7-C-β-d-glucopyranoside (2), 6,8,4′-trihydroxyflavanone-7-C-β-d-glucopyranoside (3), 8-(2-pyrrolidinone-5-yl)-catechin-3-O-β-d-allopyranoside (4), and epiphyllocoumarin-3-O-β-d-allopyranoside (5), were examined against xanthine oxidase (XOD) and in a potassium oxonate-(PTO-) induced acute hyperuricemic mice model. The results indicated that compounds3and5significantly inhibited XOD activityin vitroand reduced serum uric acid levelsin vivo. This is the first report providing new insights into the antihyperuricemic activities of flavonoid glycosides which can possibly be developed into potential hypouricemic agents.

Salvia plebeia Extract Inhibits Xanthine Oxidase Activity In Vitro and Reduces Serum Uric Acid in an Animal Model of Hyperuricemia

Planta Medica ◽  
2017 ◽  
Vol 83 (17) ◽  
pp. 1335-1341 ◽  
Author(s):  
Jin Kim ◽  
Woo Kim ◽  
Jung Hyun ◽  
Jong Lee ◽  
Jin Kwon ◽  
...  
Keyword(s):  
Animal Model ◽  
Enzyme Activity ◽  
Uric Acid ◽  
Xanthine Oxidase ◽  
Serum Uric Acid ◽  
Serum Urate ◽  
Key Enzyme ◽  
Ic50 Values

AbstractHyperuricemia is a clinical condition characterized by an elevated level of serum uric acid and is a key risk factor for the development of gout and metabolic disorders. The existing urate-lowering therapies are often impractical for certain patient populations, providing a rationale to explore new agents with improved safety and efficacy. Here, we discovered that Salvia plebeia extract inhibited the enzyme activity of xanthine oxidase, which is a key enzyme generating uric acid in the liver. In an animal model of hyperuricemia, S. plebeia extract reduced serum urate to the levels observed in control animals. The urate-lowering effect of S. plebeia extract in vivo was supported by the identification of compounds that inhibit xanthine oxidase enzyme activity in vitro. Nepetin, scutellarein, and luteolin contributed significantly to S. plebeia bioactivity in vitro. These compounds showed the highest potency against xanthine oxidase with IC50 values of 2.35, 1.74, and 1.90 µM, respectively, and were present at moderate quantities. These observations serve as a basis for further elaboration of the S. plebeia extracts for the development of new therapeutics for hyperuricemia and related diseases.

scholarly journals Anti-Hyperuricemic and Nephroprotective Effects of Dihydroberberine in Potassium Oxonate- and Hypoxanthine-Induced Hyperuricemic Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Lieqiang Xu ◽  
Guoshu Lin ◽  
Qiuxia Yu ◽  
Qiaoping Li ◽  
Liting Mai ◽  
...  
Keyword(s):  
Intragastric Administration ◽  
Inflammasome Activation ◽  
Mice Model ◽  
Protein Levels ◽  
Nlrp3 Inflammasome Activation ◽  
Mechanistic Investigation ◽  
Mrna And Protein Expression ◽  
Potassium Oxonate

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.

Application of UHPLC/ESI-Q-TOF-MS/MS to Identify Constituents of Erding Granule and Anti-hyperuricemia Effect

2019 ◽  
Vol 15 (5) ◽  
pp. 465-486 ◽  
Author(s):  
Haifang Chen ◽  
Yun Yao ◽  
Yuan Zhan ◽  
Hui Jian ◽  
Yan Li ◽  
...  
Keyword(s):  
Uric Acid ◽  
Xanthine Oxidase ◽  
Chemical Constituents ◽  
Serum Urate ◽  
Chemical Information ◽  
Upper Respiratory Tract ◽  
Serum Urate Level ◽  
Tof Ms

Background: Erding granule (EDG) widely used as an agent with the effect of heat-clearing, detoxifying, eliminating dampness, relieving jaundice and upper respiratory tract disease in clinical application, but the systematic chemical information and anti-hyperuricemia effect of EDG was still unclear. Methods: An ultra-high performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC/ESI-Q-TOF-MS/MS) method was utilized to rapidly identify the chemical constituents of EDG. The anti-hyperuricemia effect of EDG was evaluated based on the effect on xanthine oxidase inhibitory activity (in vitro) and lowering uric acid (in vivo). Results: 198 compounds were tentatively separated and identified or characterized within 30 min by UHPLC/ESI-Q-TOF MS/MS. These compounds were categorized as 22 coumarins, 38 flavones, 67 alkaloids, 36 organic acids, 16 sesquiterpenes, 14 lignans and 5 the others constituents. Meanwhile, EDG significantly decreases the serum urate level of hyperuricemic mice induced by potassium oxonate, while EDG did not significantly decrease the serum urate level of hyperuricemic mice induced by hypoxanthine and activity of xanthine oxidase in vitro. Conclusion: The method developed was rapid and sensitive to characterize the chemical constituents of EDG, and provide a systematic view of chemical information for EDG. Furthermore, we first discovered the anti-hyperuricemia effect of EDG and it would further provide the reference for clarifying the mechanism of EDG on lowering uric acid.

scholarly journals Medicinal Plants as a Drug Alternative Source for the Antigout Therapy in Morocco

Scientifica ◽  
2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Nour Elhouda Daoudi ◽  
Mohamed Bouhrim ◽  
Hayat Ouassou ◽  
Mohamed Bnouham
Keyword(s):  
Uric Acid ◽  
Side Effects ◽  
Medicinal Plants ◽  
Xanthine Oxidase ◽  
Serum Urate ◽  
Alternative Source ◽  
Xanthine Oxidase Inhibitors ◽  
High Level

Background. The gout is a metabolic disease that is associated with a high level of uric acid in the blood. This disease is treated with some medications that aim to reduce serum urate levels. However, the use of various medicines leads to the appearance of some side effects, hence the importance of using other treatments based on natural resources. Objective. This study presents some medical treatments, their side effects, and some plants that are used for gout management in Morocco in the aim to valorize them. Methods. We have been consulting various English publications in PubMed, Web of Science, and ScienceDirect published between 1991 and 2019 using the following keywords “drugs,” “gout,” “Morocco,” “medicinal plants,” “in vitro,” and “in vivo” terms. Then, we have classified the medicines, according to their action mechanisms, and we have cited some species that were reported in Moroccan pharmacopeia as antigout. Results. Three methods of the gout medical management were cited in this work: xanthine oxidase inhibitors, uric acid excretion enhancer, and uricase recombinant. However, it was found that these treatments had various side effects. We have described 23 species, and some of them showed experimentally an antigout effect by blocking the “xanthine oxidase” enzyme. These plants belong to 11 families. Lamiaceae represents the most dominant family with six species followed by Asteraceae with two species. Colchicine isolated from Colchicum autumnale is the most known compound for its efficiency towards gout. Conclusion. This work summarized different treatments particularly medicinal plants that are used in Morocco to treat gout disease by blocking uric acid secretion. However, several studies are needed to valorize these antigout natural sources.

scholarly journals In Vivo and In Vitro Evidence for the Antihyperuricemic, Anti-inflammatory and Antioxidant Effects of a Traditional Ayurvedic Medicine, Triphala

2017 ◽  
Vol 12 (10) ◽  
pp. 1934578X1701201
Author(s):  
Vilasinee Hirunpanich Sato ◽  
Bunleu Sungthong ◽  
Narawat Nuamnaichati ◽  
Prasob-orn Rinthong ◽  
Supachoke Mangmool ◽  
...  
Keyword(s):  
Uric Acid ◽  
Competitive Inhibition ◽  
Antioxidant Activities ◽  
Water Extract ◽  
Raw 264.7 Cells ◽  
Ayurvedic Medicine ◽  
Anti Inflammatory ◽  
Potassium Oxonate

The objectives of the present study were to demonstrate the antihyperuricemic effect of triphala, a formulation of traditional Ayurvedic medicine, in potassium oxonate-induced hyperuricemic mice in vivo, and to examine its inhibitor effects on xanthine oxidase (XOD), inflammatory mediators and DPPH radicals in vitro. The water extract of triphala was determined to contain the total phenolics and total flavonoids of 317.6 ± 9.2 mg GAE/g and 7.73 ± 0.26 mg QE/g, respectively. Oral administrations of triphala significantly reduced the plasma uric acid levels of potassium oxonate-induced hyperuricemic mice at doses of 1,000 and 1,500 mg/kg, as compared with control ( p<0.05). Moreover, both doses of triphala treatments markedly inhibited the formation of uric acid due to inhibition of XOD activity in liver homogenates extracted from the hyperuricemic mice by about 70-80%. Lineweaver-Burk analysis of enzyme-kinetic data showed that triphala exhibited non-competitive inhibition on XOD activity in vitro with an inhibitory constant (Ki) of 590 μg/mL. Furthermore, triphala significantly suppressed the mRNA expressions of COX-II, TNF-α and iNOS in LPS-stimulated RAW 264.7 cells, as compared with control ( p <0.05), and decreased the expression of TGF-β. IC50 values for inhibition of DPPH radical formation was calculated to be 21.9 ± 2.50 μg/mL. Antioxidant activities of triphala were determined to be 0.81 ± 0.07 g TEAC/g and 6.78 ± 0.29 mmol/100g, respectively, as assessed by ABTS and FRAP assays. In conclusion, this study provided in vivo and in vitro mechanistic evidence for the antihyperuricemic, antioxidative and anti-inflammatory effects of triphala for the first time, rationalizing its therapeutic usage for the treatment of hyperuricemia of gout.

scholarly journals Probiotic and Functional Properties of Limosilactobacillus reuteri INIA P572

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1860
Author(s):  
Patricia Diez-Echave ◽  
Izaskun Martín-Cabrejas ◽  
José Garrido-Mesa ◽  
Susana Langa ◽  
Teresa Vezza ◽  
...  
Keyword(s):  
In Vitro Assays ◽  
Immunomodulatory Activity ◽  
Probiotic Properties ◽  
Protective Effects ◽  
Mice Model ◽  
In Vivo Models ◽  
Food Borne ◽  
Gastrointestinal Conditions

Limosilactobacillus reuteri INIA P572 is a strain able to produce the antimicrobial compound reuterin in dairy products, exhibiting a protective effect against some food-borne pathogens. In this study, we investigated some probiotic properties of this strain such as resistance to gastrointestinal passage or to colonic conditions, reuterin production in a colonic environment, and immunomodulatory activity, using different in vitro and in vivo models. The results showed a high resistance of this strain to gastrointestinal conditions, as well as capacity to grow and produce reuterin in a human colonic model. Although the in vitro assays using the RAW 264.7 macrophage cell line did not demonstrate direct immunomodulatory properties, the in vivo assays using a Dextran Sulphate Sodium (DSS)-induced colitic mice model showed clear immunomodulatory and protective effects of this strain.

scholarly journals Inhibition of RANKL-Induced Osteoclastogenesis by Novel Mutant RANKL

2021 ◽  
Vol 22 (1) ◽  
pp. 434
Author(s):  
Yuria Jang ◽  
Hong Moon Sohn ◽  
Young Jong Ko ◽  
Hoon Hyun ◽  
Wonbong Lim
Keyword(s):  
Nuclear Translocation ◽  
Critical Role ◽  
Osteoclast Differentiation ◽  
Point Mutations ◽  
Tartrate Resistant Acid Phosphatase ◽  
Mice Model ◽  
Gsk 3Β ◽  
Rank Signaling

Background: Recently, it was reported that leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4, also called GPR48) is another receptor for RANKL and was shown to compete with RANK to bind RANKL and suppress canonical RANK signaling during osteoclast differentiation. The critical role of the protein triad RANK–RANKL in osteoclastogenesis has made their binding an important target for the development of drugs against osteoporosis. In this study, point-mutations were introduced in the RANKL protein based on the crystal structure of the RANKL complex and its counterpart receptor RANK, and we investigated whether LGR4 signaling in the absence of the RANK signal could lead to the inhibition of osteoclastogenesis.; Methods: The effects of point-mutated RANKL (mRANKL-MT) on osteoclastogenesis were assessed by tartrate-resistant acid phosphatase (TRAP), resorption pit formation, quantitative real-time polymerase chain reaction (qPCR), western blot, NFATc1 nuclear translocation, micro-CT and histomorphological assay in wild type RANKL (mRANKL-WT)-induced in vitro and in vivo experimental mice model. Results: As a proof of concept, treatment with the mutant RANKL led to the stimulation of GSK-3β phosphorylation, as well as the inhibition of NFATc1 translocation, mRNA expression of TRAP and OSCAR, TRAP activity, and bone resorption, in RANKL-induced mouse models; and Conclusions: The results of our study demonstrate that the mutant RANKL can be used as a therapeutic agent for osteoporosis by inhibiting RANKL-induced osteoclastogenesis via comparative inhibition of RANKL. Moreover, the mutant RANKL was found to lack the toxic side effects of most osteoporosis treatments.

scholarly journals LINGO-1 shRNA protects the brain against ischemia/reperfusion injury by inhibiting the activation of NF-κB and JAK2/STAT3

Human Cell ◽  
2021 ◽  
Author(s):  
Jiaying Zhu ◽  
Zhu Zhu ◽  
Yipin Ren ◽  
Yukang Dong ◽  
Yaqi Li ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Nuclear Translocation ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Artery Occlusion ◽  
Mice Model ◽  
Down Regulation

AbstractLINGO-1 may be involved in the pathogenesis of cerebral ischemia. However, its biological function and underlying molecular mechanism in cerebral ischemia remain to be further defined. In our study, middle cerebral artery occlusion/reperfusion (MACO/R) mice model and HT22 cell oxygen–glucose deprivation/reperfusion (OGD/R) were established to simulate the pathological process of cerebral ischemia in vivo and in vitro and to detect the relevant mechanism. We found that LINGO-1 mRNA and protein were upregulated in mice and cell models. Down-regulation LINGO-1 improved the neurological symptoms and reduced pathological changes and the infarct size of the mice after MACO/R. In addition, LINGO-1 interference alleviated apoptosis and promoted cell proliferation in HT22 of OGD/R. Moreover, down-regulation of LINGO-1 proved to inhibit nuclear translocation of p-NF-κB and reduce the expression level of p-JAK2 and p-STAT3. In conclusion, our data suggest that shLINGO-1 attenuated ischemic injury by negatively regulating NF-KB and JAK2/STAT3 pathways, highlighting a novel therapeutic target for ischemic stroke.

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