Anti-hyperuricemic Effects Research Articles

Dendrobium officinalis six nostrum ameliorates urate under-excretion and protects renal dysfunction in lipid emulsion-induced hyperuricemic rats

AimHyperuricemia (HUA) is a metabolic disease caused by the overproduction or underexcretion of uric acid (UA). Our previous study found that treatment with Dendrobium officinalis six nostrum (DOS) led to a significant reduction in serum UA (SUA) by inhibiting UA production and promoting UA excretion in a rat model of HUA induced by potassium oxonate (PO) and high-fat sorghum feed. In this study, we aimed to further investigate the effects of DOS on UA excretion by the kidney and intestine to explore whether DOS protects against histopathological changes, and to elucidate its possible mechanisms of action in a lipid emulsion (LE)-induced rat model of HUA. MethodsThe main chemical constituents of DOS were determined to be acteoside and astilbin by high-performance liquid chromatography (HPLC). Three different doses of DOS (3.3, 6.6, and 13.2 g/kg/day) were given to rats daily after induction of HUA by oral administration of LE for 8 weeks. The levels of creatinine (Cr) in serum and urine and UA in serum, urine, and feces were measured by an automatic biochemical analyzer. The expression of TLR4, NF-κB and urate transport-related transporters (URAT1, ABCG2, and PDZK1) in kidney was measured by Western blot (WB). Intestinal urate transporters (ABCG2 and GLUT9) expression was assayed by IHC and WB. Serum LPS and renal inflammatory factors (IL-6, IL-8 and TNF-α) levels were measured using enzyme-linked immunosorbent assay (ELISA) kits. Hematoxylin and eosin (H&E) staining was used to assess renal histological changes. ResultsDOS treatment significantly reduced the SUA and SCr levels by increasing urine volume, 24 h urine uric acid (UUA), fecal UA (FUA), urine creatinine (UCr), and fractional excretion of UA (FEUA) levels in hyperuricemic rats. Moreover, DOS effectively regulated URAT1, PDZK1, and ABCG2 protein levels in the kidney, as well as restored protein levels of GLUT9 and ABCG2 in the intestine. DOS markedly reduced serum LPS anddown-regulated renal TLR4 and NF-κB protein levels to suppress IL-6, IL-8, and TNF-α secretion. It also improved renal inflammation in hyperuricemic rats. In addition, DOS attenuated histopathological changes in the kidneys of LE-induced rats. HPLC analysis showed levels of acteoside and astilbin of 1.39 mg/g and 0.72 mg/g in DOS, respectively. ConclusionDOS has anti-hyperuricemic and anti-inflammatory effects in a rat model of HUA. The molecular mechanism appears to involve the regulation of urate transport-related transporters including renal ABCG2, URAT1, and PDZK1, and intestinal GLUT9 and ABCG2, as well as the inhibition of the LPS/TLR4/NF-κB signaling to reduce IL-6, IL-8, and TNF-α secretion in hyperuricemic rats.

Baicalein alleviates hyperuricemia by promoting uric acid excretion and inhibiting xanthine oxidase

BackgroundInsufficient renal urate excretion and/or overproduction of uric acid (UA) are the dominant causes of hyperuricemia. Baicalein (BAL) is widely distributed in dietary plants and has extensive biological activities, including antioxidative, anti-inflammatory and antihypertensive activities.Purpose: To investigate the anti-hyperuricemic effects of BAL and the underlying mechanisms in vitro and in vivo. MethodsWe investigated the inhibitory effects of BAL on GLUT9 and URAT1 in vitro through electrophysiological experiments and 14C-urate uptake assays. To evaluate the impact of BAL on serum and urine UA, the expression of GLUT9 and URAT1, and the activity of xanthine oxidase (XOD), we developed a mouse hyperuricemia model by potassium oxonate (PO) injection. Molecular docking analysis based on homology modeling was performed to explain the predominant efficacy of BAL compared with the other test compounds. ResultsBAL dose-dependently inhibited GLUT9 and URAT1 in a noncompetitive manner with IC50 values of 30.17 ± 8.68 μM and 31.56 ± 1.37 μM, respectively. BAL (200 mg/kg) significantly decreased serum UA and enhanced renal urate excretion in PO-induced hyperuricemic mice. Moreover, the expression of GLUT9 and URAT1 in the kidney was downregulated, and XOD activity in the serum and liver was suppressed. The docking analysis revealed that BAL potently interacted with Trp336, Asp462, Tyr71 and Gln328 of GLUT9 and Ser35 and Phe241 of URAT1. ConclusionThese results indicated that BAL exerts potent antihyperuricemic efects through renal UA excretal promotion and serum UA production. Thus, we propose that BAL may be a promising treatment for the prevention of hyperuricemia owing to its multitargeted inhibitory activity.

A Lanosteryl Triterpene (RA-3) Exhibits Antihyperuricemic and Nephroprotective Effects in Rats.

Considering the global health threat posed by kidney disease burden, a search for new nephroprotective drugs from our local flora could prove a powerful strategy to respond to this health threat. In this study we investigated the antihyperuricemic and nephroprotective potential of RA-3, a plant-derived lanosteryl triterpene. The antihyperuricemic and nephroprotective effect of RA-3 was investigated using the adenine and gentamicin induced hyperuricemic and nephrotoxicity rat model. Following the induction of hyperuricemia and nephrotoxicity, the experimental model rats (Sprague Dawley) were orally administered with RA-3 at 50 and 100 mg/kg body weight, respectively, daily for 14 days. Treatment of the experimental rats with RA-3, especially at 100 mg/kg, effectively lowered the serum renal dysfunction (blood urea nitrogen and creatinine) and hyperuricemic (uric acid and xanthine oxidase) biomarkers. These were accompanied by increased antioxidant status with decrease in malondialdehyde content. A much improved histomorphological structure of the kidney tissues was also observed in the triterpene treated groups when compared to the model control group. It is evident that RA-3 possesses the antihyperuricemic and nephroprotective properties, which could be vital for prevention and amelioration of kidney disease.

Antihyperuricemic efficacy of Scopoletin-loaded Soluplus micelles in yeast extract/potassium oxonate-induced hyperuricemic mice

Scopoletin (Sco) has great potential for hyperuricemia therapy. However, the relatively low oral bioavailability of Sco limits its further applications. Soluplus-based Sco micelles (Sco-Ms) were successfully prepared in our previous work. The oral bioavailability of Sco-Ms was increased by 438% compared with free Sco. In this study, we aimed to compare the biodistribution and antihyperuricemic efficacy of Sco and Sco-Ms, and explore their therapeutic mechanisms as well. We studied the tissue biodistribution of Sco and Sco-Ms after they were orally administered to mice. The antihyperuricemic effect and the therapeutic mechanisms of Sco and Sco-Ms were evaluated using yeast extract/potassium oxonate-induced hyperuricemia model in mice. The Sco concentration in each tissue was significantly higher than that of Sco suspension after orally administrating Sco-Ms to mice. Oral delivery of Sco-Ms exhibited significantly stronger hypouricemic efficacy in hyperuricemic mice than Sco. Meanwhile, Sco-Ms showed a better protective effect on mice kidney injury. The hypouricemic efficacy of Sco was due to promoting the excretion of uric acid via modulating the alteration of gene expression levels of renal uric acid transporter (URAT1), glucose transporter (GLUT9), and organic anion transporter 1 (OAT1). Sco-Ms could not only restore the dysregulation of URAT1, GLUT9, and OAT1 more effectively, but also down-regulate the activity of hepatic xanthine oxidase (XOD) to inhibit the production of uric acid. In conclusion, taken together, Sco-Ms represents a potential oral strategy for the treatment of hyperuricemia.

NMR-Based Metabonomic Study Reveals Intervention Effects of Polydatin on Potassium Oxonate-Induced Hyperuricemia in Rats.

Previous studies have disclosed the antihyperuricemic effect of polydatin, a natural precursor of resveratrol; however, the mechanisms of action still remain elusive. The present study was undertaken to evaluate the therapeutic effects and the underlying mechanisms of polydatin on potassium oxonate-induced hyperuricemia in rats through metabonomic technology from a holistic view. Nuclear magnetic resonance (NMR) spectroscopy was applied to capture the metabolic changes in sera and urine collected from rats induced by hyperuricemia and polydatin treatment. With multivariate data analysis, significant metabolic perturbations were observed in hyperuricemic rats compared with the healthy controls. A total of eleven and six metabolites were identified as differential metabolites related to hyperuricemia in serum and urine of rats, respectively. The proposed pathways primarily included branched-chain amino acid (BCAA) metabolism, glycolysis, the tricarboxylic acid cycle, synthesis and degradation of ketone bodies, purine metabolism, and intestinal microflora metabolism. Additionally, some metabolites indicated the risk of renal injury induced by hyperuricemia. Polydatin significantly lowered the levels of serum uric acid, creatinine, and blood urea nitrogen and alleviated the abnormal metabolic status in hyperuricemic rats by partially restoring the balance of the perturbed metabolic pathways. Our findings shed light on the understanding of the pathophysiological process of hyperuricemia and provided a reference for revealing the metabolic mechanism produced by polydatin in the treatment of hyperuricemia.

Anti-Hyperuricemic Effects of Water-Soluble Fraction of Leaf Extract of Sukun (Artocarpus Altilis) on Mice Fed Purine-Rich Foods

Introduction Hyperuricemia is a condition characterized by high levels of uric acid in the blood mainly due to its metabolic inefficiency [1]. Hyperuricemia is associated with many human diseases such as stroke incidence, chronic kidney disease, cardiovascular disease and mainly gout, an inflamm

Anti-hyperuricemic and Anti-inflammatory Effects of Marantodes pumilum as Potential Treatment for Gout.

Marantodes pumilum (Primulaceae) has been used in Malaysian folk medicine to help women regain strength after delivery and for “sickness in the bones.” It was previously revealed that its extracts inhibited xanthine oxidase (XO) activity in vitro. The leaves and roots of M. pumilum var. alata (MPA), var. pumila (MPP), and var. lanceolata (MPL) were individually extracted in ethanol (80%). The anti-hyperuricemic activity was initially assessed by XO inhibition with a spectrophotometric in vitro assay. The most active extract was further investigated on hyperuricemic rat model induced by potassium oxonate to determine serum uric acid levels and liver XO effect. The in vitro anti-inflammatory activity was carried out on monosodium urate (MSU) crystal-induced pro-inflammatory cytokines (i.e., interleukin (IL)1α, IL-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α) secretion using human peripheral blood mononuclear cells and ELISA technique, and prostaglandin E2 (PGE2)secretion using radioimmunoassay. The active extract was then investigated on gout-induced inflammation with MSU crystals to determine pro-inflammatory cytokines and PGE2 secretion levels in the synovial fluid of rat knee joint. Quantitative analysis using validated HPLC was performed on the extracts to determine presence of bioactive flavonoids. The findings revealed that extract of MPP leaves gave the highest inhibitory activity on XO (IC50 130.5 μg/mL) compared to other extracts tested. However, all extracts possessed significantly lower activity compared to allopurinol (IC50 0.13 μg/mL). Oral administration of MPP leaf extract (200 mg/kg) significantly reduced serum uric acid level in hyperuricemic rats in time-dependent manner to the baseline level and it was as effective as allopurinol (5 mg/kg). The extract also inhibited liver XO activity (25%) compared to allopurinol (45%). In vitro anti-inflammatory assay showed that extract of MPP roots inhibited MSU crystals-induced secretion of IL-1α, IL-1β, IL-8, TNF-α, and PGE2 with IC50 values of 36, 25, 38, 18, and 46 μg/mL, respectively. Oral administration of the MPP root extract (200 mg/kg) significantly decreased IL-1α, IL-1β, IL-6, TNF-α, and PGE2 levels in rat’s synovial fluid as effective as indomethacin. There were no significant body weight changes of all experimental animals. MPP extracts showed presence of myricetin, quercetin and kaempferol. Myricetin was detected with values of 0.2 and 0.6 mg/g for root and leaf extracts, respectively. The anti-hyperuricemic of MPP leaf and anti-inflammatory of MPP root indicated that MPP may be promising for complementary therapy of gout.

Anti-hyperuricemic effects of three theaflavins isolated from black tea in hyperuricemic mice

• TF, TFDG and TF-3-G down-regulated the genes and proteins expression of GLUT9 and URAT1. • TF, TFDG and TF-3-G up-regulated the gene and protein expression of OAT1 and the genes expression of ABCG2, OCTN1, OCT1/2, and OAT2. • TF, TFDG and TF-3-G ameliorate the kidney damages of hyperuricemic mice. Theaflavins are characteristic ingredients of black tea which are correlated with their qualities and functions. The study aimed to evaluate the effects and mechanism of major theaflavin monomers reducing serum uric acid (SUA) in hyperuricemic mice. Three theaflavin monomers of TF, TFDG and TF-3-G were isolated and purified from black tea. The results showed that they have obvious SUA-lowering effect on hyperuricemic mice. They suppressed the activities of ADA and XOD, down-regulated the genes and proteins expression of GLUT9 and URAT1, up-regulated the gene and protein expression of OAT1 and the genes expression of ABCG2, OCTN1, OCT1/2, and OAT2. They could also decrease serum BUN and Cr values and improve renal damages of hyperuricemic mice. The mechanism might be correlation with reducing the amount of inflammatory cells and activating Nrf2/HO-1 pathway. These findings indicated that TF, TFDG and TF-3-G could have potential application prospects in prevention and therapy of hyperuricemia.

Antihyperuricemic and nephroprotective effects of extracts from Orthosiphon stamineus in hyperuricemic mice

To investigate the antihyperuricemia and nephroprotective effects of Orthosiphon stamineus extracts on hyperuricemia (HUA) mice and explore the potential mechanisms. 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). 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. 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.

Anti-hyperuricemic and Nephroprotective Effects of Barley Leaf Powder in Hyperuricemic Mice

To investigate the anti-hyperuricemic and nephroprotective effects of barley leaf powder (BLP) in hyperuricemic mice and the underlying mechanisms, hyperuricemia in mice via intraperitoneal injection of potassium oxazinate were induced, and the effects by measuring the serum uric acid (UA), urine UA, feces UA, serum creatinine (CR), urea nitrogen (BUN), serum and hepatic xanthine oxidase (XOD) activities were evaluated, the pathological changes of the kidney tissues by HE staining were observed. Besides, the mRNA expression levels of urate transporters including urate transporter 1 (URAT1), glucose transporter 9 (GLUT9) and organic anion transporter 1 (OAT1) were detected to explore mechanisms of the anti-hyperuricemic and nephroprotective effects of BLP. Results showed that, compared with the model group, BLP at 200 mg/kg could highly significantly reduce the serum UA level (P<0.001), promote the excretion of UA from urine (P<0.001) and extremely significantly promote the UA excretion in feces (P<0.01). Meanwhile, BLP highly significantly reduced the serum and hepatic XOD activities as well as the production of liver UA at 200 mg/kg (P<0.001). In addition, compared with the model group, 200 mg/kg BLP could extremely significantly reduce the elevated serum CR (P<0.01) and highly significantly reduce the BUN levels caused by hyperuricemia (P<0.001), as proved by the pathological analysis of the kidney tissues. Data from qRT-PCR assays showed that 200 mg/kg BLP highly significantly (P<0.001) downregulated URAT1 and GLUT9 and upregulated OAT1 expressions compared with the model group. In summary, the anti-hyperuricemic and nephroprotective effects of BLP may be mediated by regulation of XOD, URAT1, GLUT9 and OAT1.

Empagliflozin Attenuates Hyperuricemia by Upregulation of ABCG2 via AMPK/AKT/CREB Signaling Pathway in Type 2 Diabetic Mice.

Hyperuricemia (HUA) is a metabolic disease characterized by elevated serum uric acid (SUA). Empagliflozin, a kind of sodium-glucose cotransporter 2 inhibitors, has recently emerged as a new antidiabetic agent by facilitating glucose excretion in urine. Moreover, there was evidence of SUA reduction following treatment with empagliflozin in addition to glycaemic control, while the molecular mechanisms remain unknown. To investigate the potential mechanisms, the model of type 2 diabetes (T2DM) with HUA was established by combination of peritoneal injection of potassium oxonate and intragastric administration of hypoxanthine in KK-Ay mice. A series of method such as RT-PCR, western blot, immunochemistry, immunofluorescence were conducted to explore the mechanism. Our results showed that empagliflozin significantly ameliorated the levels of SUA and blood glucose in T2DM mice with HUA. Furthermore, in both kidney and ileum, empagliflozin obviously promoted protein expression of uric acid (UA) transporter ABCG2, p-AMPK, p-AKT and p-CREB. The same trend was observed in human tubular epithelial (HK-2) cells. Additionally, through application of an AMPK inhibitor (Compound C), it was further confirmed empagliflozin exerted its anti-hyperuricemic effects in an AMPK dependent manner. Meanwhile, with the help of ChIP assay and luciferase reporter gene assay, we found that CREB further activated ABCG2 via binding to the promoter of ABCG2 to induce transcription. Taken together, our study demonstrated that empagliflozin treatment played an essential role in attenuating HUA by upregulation of ABCG2 via AMPK/AKT/CREB signaling pathway.

Comparisons of protective effects between two sea cucumber hydrolysates against diet induced hyperuricemia and renal inflammation in mice.

Hyperuricemia is an important risk factor for many diseases including hypertension and type 2 diabetes. This study investigated and compared the effects of hydrolysates of two sea cucumber species, Apostichopus japonicus and Acaudina leucoprocta, on the alleviation of diet-induced hyperuricemia and renal inflammation. The structure and abundance of oligopeptides in enzymatic hydrolysates of A. japonicus (EH-JAP) and A. leucoprocta (EH-LEU) were identified via MALDI-TOF/TOF-MS, and the anti-hyperuricemic and anti-inflammatory effects of the hydrolysates were explored in a diet-induced hyperuricemic mouse model. Both EH-JAP and EH-LEU inhibit uric acid biosynthesis and promote uric acid excretion, leading to the alleviation of the hyperuricemic phenotype. In addition, these two treatments down-regulated the transcription of pro-inflammatory cytokines, up-regulated the transcription of anti-inflammatory cytokines, and inhibited the activation of the Toll-like receptor 4/myeloid differentiation factor 88/NF-kappaB (TLR4/MyD88/NF-κB) signaling pathway, leading to the alleviation of renal inflammation. EH-JAP had better effects than EH-LEU due to differences in their regulation of uric acid biosynthesis, uric acid excretion and release of anti-inflammatory cytokines. In addition, EH-JAP and EH-LEU treatment alleviated the dysfunction of the gut microbiota by increasing the abundance of beneficial Lactobacillus and short-chain fatty acid producers and decreasing the abundance of opportunistic pathogens. This study provides a valuable reference for the development of sea cucumber applications.

Phytochemical analysis and evaluation of purified extract of Tinospora crispa stem for in vivo antihyperuricemic effect

Background: Tinospora crispa is used in folk medicines for the treatment of gout, rheumatoid arthritis, and internal inflammation. The presence of flavonoids, polyphenols, glycosides, and alkaloids in T. crispa stem is supposed to contribute to these therapeutic effects. This study aimed to analyze qualitative and quantitative phytochemical of purified extract of T. crispa stem (PETS) and to evaluate the in vivo antihyperuricemic effect. Materials and Methods: First, total flavonoid and total alkaloid contents of PETS were determined by colorimetric and gravimetric methods. After that, potassium oxonate-induced hyperuricemic mice were treated with three doses of PETS at 50, 100, and 200 mg/kg, and hydroalcoholic extract at 500 mg/kg. Moreover, allopurinol at 10 mg/kg and sodium carboxymethylcellulose 0.5% were orally administered as positive and negative controls, respectively. Serum uric acid levels were measured by ultraviolet–visible spectrophotometry. Results: The high flavonoids content (31.08% ± 1.77% rutin equivalent) in T. crispa stem possesses a potential as uricostatic in the treatment of gout. The purified extract of T. crispa stem at a dose of 100 mg/kg revealed a significant uric acid–lowering effect compared with negative control (P < 0.05). Conclusion: This study indicates the potential of T. crispa purified extracts in the treatment of hyperuricemia and gout.

Antihyperuricemic effect of dietary polyphenol sinapic acid commonly present in various edible food plants.

The present study was conducted to evaluate the antihyperuricemic effect of sinapic acid (SA). The results showed that SA potently inhibited xanthine oxidase (XOD) in a dose-dependent manner by entering the enzyme active site and thwarting the entrance of the substrate. These results were further confirmed by the quantum chemical descriptors analysis and 1 H NMR titration analysis. The in vivo results indicated that SA not only has the potential to inhibit serum and hepatic XOD (p<.05), but also remarkably lowered serum and urine uric acid levels at 50 and 100mg/kg bw. Furthermore, SA regulated serum creatinine and blood urea nitrogen levels to normal and lowered inflammation in the renal tubules. Thus, the utilization of SA as an antihyperuricemic agent may have considerable potential for the development of functional foods for the possible treatment of hyperuricemia. PRACTICAL APPLICATIONS: Plant-derived bioactive compounds have multiple health benefits. The present study assesses the effects of sinapic acid against hyperuricemia. The results suggested that sinapic acid may have a strong protective effect against uric acid-related complications and may be used for the formulation of functional foods. However, further mechanistic studies are required to verify this hypothesis.

Anti-hyperuricemic and nephroprotective effect of geniposide in chronic hyperuricemia mice

Hyperuricemia is a key risk factor for kidney disease. Geniposide possesses various pharmacological activities, however, to our knowledge, no previous work investigated the therapeutic effect of geniposide on urate nephropathy. The present study established a chronic hyperuricemia model using a combination of adenine and ethambutol administration. The potential beneficial effects and mechanisms of geniposide on hyperuricemia and nephropathy were also investigated. The results demonstrated that geniposide significantly decreased SUA levels via inhibition of the XOD activity and increasing the excretion of urinary uric acid. Geniposide also markedly improved kidney damage related to hyperuricemia. Further investigation indicated that geniposide improved the symptoms of nephropathy via decreasing the production of proinflammatory cytokines, including IL-1β, PG-E2, and TNF-α, and inhibiting the expression of TGF-β1. The molecular mechanism of action may be associated with suppression of TLR4/MyD88 signaling and NLRP3 inflammasome activation to reduce IL-1β and TNF-α production respectively in hyperuricemic mice.

Curcumin attenuates potassium oxonate-induced hyperuricemia and kidney inflammation in mice

Current evidences suggest that hyperuricemia is closely related to the overproduction or underexcretion of uric acid (UA). Curcumin (CUR), a natural polyphenol component extracted from the rhizome of Curcuma longa, has been reported to treat various symptoms such inflammation disease, seems to be efficacious in hyperuricemia. In this study, we aimed to investigate the effect of CUR on hyperuricemia and kidney inflammation in hyperuricemic mice. Administration with CUR (20 or 40 mg/kg) or allopurinol (ALL, 5 mg/kg) was given to mice orally one hour later after the injection of potassium oxonate (PO) (300 mg/kg, i.p.) for 14 days. CUR administration decreased the levels of uric acid (UA), creatinine (CRE) and blood urea nitrogen (BUN) in serum. Meanwhile, treatment with CUR effectively inhibited serum and liver xanthine oxidase (XOD) levels, and further renewed normal antioxidant enzymes activities (SOD, GSH-Px), reduced MDA accumulation in serum. Further studies showed that CUR decreased inflammatory cytokines productions (IL-1β, IL-18) in serum, as well as inhibited PO-induced the activation of NLRP3 inflammasome signaling in the kidney. In conclusion, the study revealed that CUR exhibited anti-hyperuricemic and anti-inflammatory effects through suppressing NLRP3 inflammasome activation in kidney and provided the evidence for treating hyperuricemia and associated renal inflammation.

Lychnophora pinaster ethanolic extract and its chemical constituents ameliorate hyperuricemia and related inflammation

Ethnopharmacological relevanceLychnophora pinaster, known as “Brazilian arnica” is used in folk medicine as alcoholic extract to treat inflammation, pain, rheumatism and bruises. Aim of the studyEvaluate the effects of the Lychnophora pinaster's ethanolic extract and its chemical constituents on inflammation and hyperuricemia. Materials and methodsEthanolic and hexanic extracts were obtained from the aerial parts of L. pinaster. Sesquiterpene E-lychnophoric acid was isolated from hexanic extract and identified by RMN, GC/MS and IR. In vivo anti-hyperuricemic and anti-inflammatory effects of the ethanolic extracts from L. pinaster (40, 125, 375 mg/kg), E-lychnophoric acid and other constituents previous isolated from L. pinaster and identified in the ethanolic extract by HPLC/UV/DAD (rutin, quercetin and vitexina flavonoids, caffeic, cinnamic and chlorogenic acids, lupeol and stigmasterol, at dose of 15 mg/kg) were assayed by experimental model of oxonate-induced hyperuricemia in Swiss mice, liver xanthine oxidase (XOD) inhibition and by MSU-induced paw edema in mice. ResultsEthanolic extract and all its components presented anti-hyperuricemic activity by inhibiting the hepatic xanthine oxidase activity. Ethanolic extract and its chemical constituents, except quercetin and vitexin, were able to reduce paw edema size induced by urate crystals. Hypouricemic and anti-inflammatory results obtained for the ethanolic extract (40, 125, 375 mg/kg) and E-lychnophoric acid (15 mg/kg) were similar those obtained for standard drugs, allopurinol (10 mg/kg) and indomethacin (3 mg/kg). ConclusionEthanolic extract and E-lychnophoric, chlorogenic, cinnamic and caffeic acids, rutin, lupeol and stigmasterol presented anti-inflammatory and anti-hyperuricemic actvities. These compounds are responsible for the activities presented by the ethanolic extract of L. pinaster. Ethanolic extract and its chemical constituents can be considered promising agents in the therapeutic of inflammation, hyperuricemia and gout.

Enhancement of Oral Bioavailability and Anti-hyperuricemic Activity of Isoliquiritigenin via Self-Microemulsifying Drug Delivery System.

The aim of this study was to develop a self-microemulsifying drug delivery system (SMEDDS) for enhancement of the oral bioavailability of isoliquiritigenin (ISL) as well as evaluate its in vivo anti-hyperuricemic effect in rats. The ISL-loaded self-microemulsifying drug delivery system (ISL-SMEDDS) was comprised of ethyl oleate (EO, oil phase), Tween 80 (surfactant), and PEG 400 (co-surfactant). The ISL-SMEDDS exhibited an acceptable narrow size distribution (44.78 ± 0.35nm), negative zeta potential (- 10.67 ± 0.86mV), and high encapsulation efficiency (98.17 ± 0.24%). The in vitro release study indicated that the release rates of the formulation were obviously higher in different release media (HCl, pH1.2; PBS, pH6.8; double-distilled water, pH7.0) compared with the ISL solution. The oral bioavailability of the ISL-SMEDDS was enhanced by 4.71 times in comparison with the free ISL solution. More importantly, ISL-SMEDDS significantly reduced uric acid level by inhibiting xanthine oxidase (XOD) activity in the model rats. Collectively, the prepared ISL-SMEDDS proved to be potential carriers for enhancing the solubility and oral bioavailability of ISL, as well as ameliorating its anti-hyperuricemic effect.

Termipaniculatones A-F, chalcone-flavonone heterodimers from Terminthia paniculata, and their protective effects on hyperuricemia and acute gouty arthritis

Terminthia paniculata (Sanyeqi) is widely used for treating inflammation and rheumatic arthritis in the folk areas of Yunnan province, China. Its total extract was first revealed with xanthine oxidase (XO) inhibitory activity in vitro and anti-hyperuricemic effect in vivo. Bioassay-guided separation on Fr. A5 yielded six chalcone-flavonone heterodimers, termipaniculatones A-F. Their structures were elucidated based on extensive spectroscopic analyses involving HRESIMS, 1D and 2D NMR, UV, IR and [α]D, and the absolute configuration of termipaniculatone F was verified by ECD calculation. Termipaniculatones A and E showed obvious XO inhibitory activity with IC50 values of 55.6 and 89.5 μM, respectively, which took effects via a mix-type mode. A molecular modeling study revealed that termipaniculatone A was well located into the active site of XO by interacting with Glu802, Arg880, Thr1010 and Val1011 residues. Termipaniculatone A showed anti-hyperuricemic effects by decreasing serum uric acid levels and inhibiting XO activity in both serum and liver on potassium oxonate (PO)-induced hyperuricemia mice, and anti-inflammatory activity through alleviating paw swelling on monosodium urate (MSU)-induced mice, at the concentration of 20 mg/kg. This is the first time to reveal the anti-hyperuricemic and anti-acute gouty arthritis potency of T. paniculata and the characteristic biflavonoids as active constituents, which provides valuable information for searching new XO inhibitors from natural sources.

Anti-hyperuricemic effect of Alpinia oxyphylla seed extract by enhancing uric acid excretion in the kidney

BackgroundAlpinia oxyphylla is a well-known traditional medicine used in China and Korea to treat intestinal disorders, urosis, diuresis, and chronic glomerulonephritis. PurposeWe investigated the anti-hyperuricemic effects of Alpinia oxyphylla seed extract (AE), and the underlying mechanisms of action through in vitro and in vivo studies. MethodsWe evaluated levels of uric acid in the serum and urine, the expression of renal urate transport proteins, and levels of inflammatory cytokines in potassium oxonate (PO)-induced hyperuricemic rats. Xanthine oxidase activity was analyzed in vitro, while cellular uric acid uptake was assessed in oocytes expressing the human urate transporter 1 (hURAT1). Moreover, the main components of AE were analyzed using UPLC. ResultsIn PO-induced hyperuricemic rats, 200 and 400 mg/kg of AE significantly decreased levels of uric acid in serum, while 400 mg/kg of AE increased uric acid levels in urine. AE did not inhibit xanthine oxidase in vitro; however, 1, 10, and 100 μg/ml of AE significantly decreased uric acid uptake into oocytes expressing hURAT1. Furthermore, 400 mg/kg of AE increased levels of organic anion transporter (OAT) 1 protein, while 200 and 400 mg/kg of AE decreased the protein content of urate transporter, URAT1 and inflammatory cytokines in the kidneys. Nootkatone was identified as one the main chemical components in AE from UPLC analysis. ConclusionsThese findings suggest that AE exerts anti-hyperuricemic and uricosuric effects, which are related to the promotion of uric acid excretion via enhanced secretion and inhibition of uric acid reabsorption in the kidneys. Thus, AE may be a potential treatment for hyperuricemia and gout.