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

BACKGROUND: α-Viniferin, the major constituent of the roots of Caragana sinica (Buc'hoz) Rehder with a trimeric resveratrol oligostilbenoid skeleton, was demonstrated to possess a strong inhibitory effect on xanthine oxidase in vitro, suggesting it to be a potential anti-hyperuricemia agent. However, the in vivo anti-hyperuricemia effect and its underlying mechanism were still unknown. PURPOSE: The current study aimed to evaluate the anti-hyperuricemia effect of α-viniferin in a mouse model and to assess its safety profile with emphasis on its protective effect on hyperuricemia-induced renal injury. METHODS: The effects were assessed in a potassium oxonate (PO)- and hypoxanthine (HX)-induced hyperuricemia mice model by analyzing the levels of serum uric acid (SUA), urine uric acid (UUA), serum creatinine (SCRE), serum urea nitrogen (SBUN), and histological changes. Western blotting and transcriptomic analysis were used to identify the genes, proteins, and signaling pathways involved. RESULTS: α-Viniferin treatment significantly reduced SUA levels and markedly mitigated hyperuricemia-induced kidney injury in the hyperuricemia mice. Besides, α-viniferin did not show any obvious toxicity in mice. Research into the mechanism of action of α-viniferin revealed that it not only inhibited uric acid formation by acting as an XOD inhibitor, but also reduced uric acid absorption by acting as a GLUT9 and URAT1 dual inhibitor as well as promoted uric acid excretion by acting as a ABCG2 and OAT1 dual activator. Then, 54 differentially expressed (log2 FPKM ≥ 1.5, p ≤ 0.01) genes (DEGs) repressed by the treatment of α-viniferin in the hyperuricemia mice were identified in the kidney. Finally, gene annotation results revealed that downregulation of S100A9 in the IL-17 pathway, of CCR5 and PIK3R5 in the chemokine signaling pathway, and of TLR2, ITGA4, and PIK3R5 in the PI3K-AKT signaling pathway were involved in the protective effect of α-viniferin on the hyperuricemia-induced renal injury. CONCLUSIONS: α-Viniferin inhibited the production of uric acid through down-regulation of XOD in hyperuricemia mice. Besides, it also down-regulated the expressions of URAT1 and GLUT9 and up-regulated the expressions of ABCG2 and OAT1 to promote the excretion of uric acid. α-Viniferin could prevent hyperuricemia mice from renal damage by regulating the IL-17, chemokine, and PI3K-AKT signaling pathways. Collectively, α-viniferin was a promising antihyperuricemia agent with desirable safety profile. This is the first report of α-viniferin as an antihyperuricemia agent.

Antihyperuricemia and antigouty arthritis effects of Persicaria capitata herba in mice.

BACKGROUND: Hyperuricemia (HUA) is an important risk factor for gout, renal dysfunction and cardiovascular diseases. The whole plant of Persicaria capitata (Buch.-Ham. ex D. Don) H. Gross, namely Persicaria capitata herba, is a well-known ethnic herb with potent therapeutic effects on urinary tract infections and urinary calculus, yet previous reports have only focused on its effect on urinary tract infections. PURPOSE: To evaluate the therapeutic potential of P. capitata herba against gout by investigating its antihyperuricemia and antigouty arthritis effects and possible mechanisms. METHODS: The ethanol extract (EP) and water extract (WP) of P. capitata herba were prepared by extracting dried and ground whole plants of P. capitata with 75% ethanol and water, respectively, followed by removal of solvents and characterization by UHPLC-Q-TOF/MS. The antihyperuricemia and antigouty arthritis effects of the two extracts were evaluated in a potassium oxonate- and hypoxanthine-induced hyperuricemia mouse model and a monosodium urate crystal (MSUC)-induced acute gouty arthritis mouse model, respectively. The mechanisms were investigated by testing their effects on the expression of correlated proteins (by Western blot) and mRNAs (by RT-PCR). RESULTS: UHPLC-HRMS fingerprinting and two chemical markers (i.e., quercetin and quercitrin) determination were used for the characterization of the WP and EP extracts. Both WP and EP extracts showed pronounced antihyperuricemia activities, with a remarkable decline in serum uric acid and a marked increase in urine uric acid in hyperuricemic mice. Unlike the clinical xanthine oxidase (XOD) inhibitor allopurinol, WP and EP did not show any distinct renal toxicities. The underlying antihyperuricemia mechanism involves the inhibition of the activity and expression of XOD and the downregulation of the mRNA and protein expression of glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1). The extracts of P. capitata herba also demonstrated remarkable anti-inflammatory activity in MSUC-induced acute gouty arthritis mice. The mechanism might involve inhibitory effects on the expression of proinflammatory factors. CONCLUSIONS: The extracts of P. capitata herba possessed pronounced antihyperuricemia and antigouty arthritis effects and were, therefore, promising natural medicines for hyperuricemia-related disorders and gouty arthritis. The use of P. capitata herba for the treatment of urinary calculus may be, at least to some degree, related to its potential as an antihyperuricemia and antigouty arthritis drug.

Prelimbic α1-adrenoceptors are involved in the regulation of depressive-like behaviors in the hemiparkinsonian rats.

At present, it is not clear whether α1-adrenoceptors in the prelimbic cortex (PrL) are involved in Parkinson's disease-related depression. Here we examined effects of PrL α1-adrenoceptors on depressive-like behaviors in rats with unilateral 6-hydroxydopamine lesions of the medial forebrain bundle. The lesion induced depressive-like responses as measured by the sucrose preference and forced swim tests compared to sham-operated rats. Intra-PrL injection of α1-adrenoceptor agonist phenylephrine induced or increased the expression of depressive-like behaviors in sham-operated and the lesioned rats. Further, intra-PrL injection of α1-adrenoceptor antagonist benoxathian produced antidepressant effects in two groups of rats. Intra-PrL injection of phenylephrine increased the mean firing rate of PrL pyramidal neurons in both sham-operated and the lesioned rats, while benoxathian decreased the mean firing rate of the neurons. Compared to sham-operated rats, the duration of phenylephrine and benoxathian action on the firing rate of the pyramidal neurons was shortened in the lesioned rats. Neurochemical results showed that intra-PrL injection of phenylephrine or benoxathian increased or decreased dopamine and noradrenaline and serotonin levels in the medial prefrontal cortex, ventral hippocampus and habenula in sham-operated and the lesioned rats, respectively. Altogether, these results suggest that activation and blockade of α1-adrenoceptors in the PrL change the firing activity of the pyramidal neurons, and then increase or decrease levels of three monoamines in the limbic and limbic-related brain regions, which are involved in the regulation of depressive-like behaviors. Additionally, the results also suggest that the dopaminergic lesion leads to hypofunctionality of α1-adrenoceptors on pyramidal neurons of the PrL.

[Study on UIPLC-DAD fingerprint of Disporum cantoniense].

OBJECTIVE: To establish an UHPLC-DAD fingerprint of 30 batches of Miao medicine Disporum cantoniense from Guizhou, and to provide a theoretical evidence to evaluate its quality. METHODS: The analysis was carried out on an Agilent Eclipse ZOR-BAX Plus C18 (100 mm x 2. 1 mm, 1. 8 µm) column with a mobile phase consisting of acetonitrile-water(containing 0. 1% formic acid) with gradient elution, and the flow rate was 0. 3 mL/min. The column temperature was set at 40 °C and UV detection wavelength was set at 290 nm. The sample injection volume was 3 µL. The similarity evaluation and principal component analysis(PCA) of these fingerprints were carried out. RESULTS: The UHPLC-DAD fingerprint was established and compared by 30 batches of samples similarity with 12 common peaks and 3 peaks were identified. The similarities of 30 batches of Disporum cantoniense were between 0. 766 and 0. 994. The principal component analysis showed that compounds 1 and 12 were representative for the fingerprint. CONCLUSION: The method is accurate and credible,which can be used for identification and quality control of Disporum cantoniense.

[Detection of trace uranium in air with field spectrometry].

As a natural radioactive element, uranium and its compounds exist as aerosol and transfer in air. In gas phase, uranium can cause various kinds of radioactive damage to human body. The change in its concentration in a local area is related to the exploration and utilization of nuclear energy. Therefore, the development of field method for rapid uranium detection in air sample is very important. In this contribution, the air samples over uranium ores collected by a general pump was absorbed with 2.0 mol x L(-1) nitrate and then reacted with solid reagent kit. When the reaction between trace uranium and chromogenic reagent was finished, the homemade portable photometer was used to measure the absorbance. The results showed that the concentration of uranium in air samples over low grade uranium ores can be successfully determined by the present method and the values agree with that obtained by ICP-MS. The RSD measured by the new method was 1.72%. The application of the new field spectrometry in discriminating uranium ores from other ores has the potential advantages of easy operation, cost-saving and high accuracy.

Radioactivity concentrations in soils of the Xiazhuang granite area, China.

The natural radioactivity of soils at the Xiazhuang granite massif of Southern China has been studied. The radioactivities of 55 samples have been measured with a low-background HPGe detector. The radioactivity concentrations of (238)U and (40)K ranged from 40.2 to 442 and from 442 to 913 Bq/kg, respectively, while the radioactivity concentration of (232)Th varied only slightly. In order to evaluate the radiological hazard of the natural radioactivity, the radium equivalent activity (Ra(eq)), the absorbed dose rate (D ), the annual effective dose rate and the external hazard index (H(ex)) have been calculated and compared with the internationally approved values. The study provides background radioactivity concentrations in a granite area, specifically, the area in the vicinity of a uranium mine in Southern China. The data can be used in exploring granite-type uranium deposits.