Astragalus membranaceus ultrafine powder alleviates hyperuricemia by regulating the gut microbiome and reversing bile acid and adrenal hormone biosynthesis dysregulation

Ethnopharmacological relevanceMetabolic syndrome is closely related to the intestinal microbiota and disturbances in the host metabolome. Hyperuricemia (HUA), a manifestation of metabolic syndrome, can induce various cardiovascular diseases and gout, seriously affecting a patient’s quality of life. Astragalus membranaceus has a long history as a commonly used traditional Chinese medicine to treat kidney disease in China and East Asia.Materials and methodsWe compared the therapeutic effect of benzbromarone and two different doses Astragalus membranaceus ultrafine powder (AMUP) in rats with HUA. Ultra-performance liquid chromatography-mass spectrometer was used to analyze the AMUP metabolism in the plasma, urine, and feces. Further, 16S ribosome RNA sequencing and feces metabolomic were performed to capture the variation of the gut microbiota and metabolites changes before and after drug administration.ResultsAMUP had a notable impact on reducing blood uric acid levels while protecting the liver and kidney. Drug metabolism analysis demonstrated that effective constituent flavonoids are distributed in the blood, whereas saponins remain in the intestine. Gut microbiota analysis showed that low-dose AMUP ameliorated HUA-induced gut dysbiosis by reducing the abundance of harmful bacteria and increasing that of some beneficial bacteria with anti-inflammatory properties, such as Clostridia, Lachnospiraceae, and Muribaculaceae. In addition, HUA-induced changes in metabolite contents in bile acid and adrenal hormone biosynthesis pathways were restored after treatment with AMUP.ConclusionLow-dose AMUP exerts remarkable therapeutic effects on HUA by regulating the gut microbiome and mediating gut metabolism pathways associated with uric acid excretion.     

Separation ofN-carbamoyl aspartate andl-dihydroorotate from serum by high-performance liquid chromatography with fluorimetric detection

Summary A high-performance liquid chromatographic method, with 9-anthryldiazomethane as derivatizing agent, has been developed for the simultaneous determination ofN-carbamoyl aspartate andl-dihydroorotate in serum. Sample preparation for 1 mL serum was by simple liquid-liquid extraction and then derivatization. The compounds were separated on a Luna C18(2) column by use of a gradient prepared from acetonitrile and 10 mM sodium acetate buffer, pH 6.0, and fluorimetric detection was performed at excitation and emission wavelengths of 365 nm and 412 nm, respectively. The response was found to be linearly dependent on concentration between 0.8 and 60 μg mL⁻¹ forl-dihydrooratate and between 0.9 and 90 μg mL⁻¹ forN-carbamoyl aspartate; the mean recovery rates were 50 and 51%, respectively. The limits of detection and quantification were 0.33 μg mL⁻¹ and 0.6 μg mL⁻¹, respectively, forl-dihydroorotate and 0.4 μg mL⁻¹ and 0.7 μg mL⁻¹ forN-carbamoyl aspartate. This method can be used to assess accumulation ofN-carbamoyl aspartate andl-dihydroorotate in body fluids in situations where cellular pyrimidine de novo synthesis is impaired.     

Wound Healing Attributes of Polyelectrolyte Multilayers Prepared with Multi‐l‐arginyl‐poly‐l‐aspartate Pairing with Hyaluronic Acid and γ‐Polyglutamic Acid

Biodegradable multi‐l ‐arginyl‐poly‐l ‐aspartate (MAPA), more commonly cyanophycin, prepared with recombinant Escherichia coli contains a polyaspartate backbone with lysine and arginine as side chains. Two assemblies of polyelectrolyte multilayers (PEMs) are fabricated at three different concentration ratios of insoluble MAPA (iMAPA) with hyaluronic acid (iMAPA/HA) and with γ‐polyglutamic acid (iMAPA/γ‐PGA), respectively, utilizing a layer‐by‐layer approach. Both films with iMAPA and its counterpart, HA or γ‐PGA, as the terminal layer are prepared to assess the effect on film roughness, cell growth, and cell migration. iMAPA incorporation is higher for a higher concentration of the anionic polymer due to better charge interaction. The iMAPA/HA films when compared to iMAPA/γ‐PGA multilayers show least roughness. The growth rates of L929 fibroblast cells on the PEMs are similar to those on glass substrate, with no supplementary effect of the terminal layer. However, the migration rates of L929 cells increase for all PEMs. γ‐PGA incorporated films impart 50% enhancement to the cell migration after 12 h of culture as compared to the untreated glass, and the smooth films containing HA display a maximum 82% improvement. The results present the use of iMAPA to construct a new layer‐by‐layer system of polyelectrolyte biopolymers with a potential application in wound dressing.     

基于N-((3-吡啶基)磺酰基)天冬氨酸的Co(Ⅱ)、Zn(Ⅱ)、Cd(Ⅱ)配位聚合物的合成、磁性和荧光性质

以N-((3-吡啶基)磺酰基)天冬氨酸(H₂L)为配体,采取水热合成的方法,合成了配位聚合物[M(HL)₂]_n(M=Co,1;Zn,2;Cd,3)。X射线单晶衍射分析表明,它们的晶体同构。1的磁性分析表明,1的Curie常数为4.66cm³·mol^-1·K,Curie-Weiss常数为-21.23K;与配体H₂L相比,2和3的发射光谱发生了明显的蓝移,可能归因于配体到金属的电荷转移。     

Application of high field spectroscopic imaging in the evaluation of temporal lobe epilepsy

Previous spectroscopic imaging studies of temporal lobe epilepsy have used comparisons of metabolite content or ratios to lateralize the seizure focus. Although highly successful, these studies have shown significant variations within each of the groups of healthy subjects and patients. This variation may arise from the natural differences seen in metabolite concentration in gray and white matter, the complex anatomy seen about the hippocampus, and the large voxels typically employed at 1.5 T. Using a 4.1 T whole body system, we have acquired spectroscopic images with 0.5 cc nominal voxels (1 cc after filtering) to evaluate the regional variation in metabolite content of the hippocampus, temporal gray and white matter, midbrain, and cerebellar vermis. Using a threshold value of 0.90 for CR/NAA, a value 90% of all normal hippocampal voxels lay below, we have correctly identified the presence of epileptogenic tissue in patients with unilateral as well as bilateral seizures. By using comparisons to healthy values of the CR/NAA ratio, this method enables the visualization of bilateral disease and provides information on the extent of gray matter involvement.     

Monitoring of metabolic profiling and water status of Hayward kiwifruits by nuclear magnetic resonance

The metabolic profiling of kiwifruit (Actinidia deliciosa, Hayward cultivar) aqueous extracts and the water status of entire kiwifruits were monitored over the season (June-December) using nuclear magnetic resonance (NMR) methodologies. The metabolic profiling of aqueous kiwifruit extracts was investigated by means of high field NMR spectroscopy. A large number of water-soluble metabolites were assigned by means of 1D and 2D NMR experiments. The change in the metabolic profiles monitored over the season allowed the kiwifruit development to be investigated. Specific temporal trends of aminoacids, sugars, organic acids and other metabolites were observed.The water status of kiwifruits was monitored directly on the intact fruit measuring the T₂ spin-spin relaxation time by means of a portable unilateral NMR instrument, fully non-invasive. Again, clear trends of the relaxation time were observed during the monitoring period.The results show that the monitoring of the metabolic profiling and the monitoring of the water status are two complementary means suitable to have a complete view of the investigated fruit.     

The Preparation of β-Cycloalkyl-L-Aspartate and γ-Cycloalkyl-L-Glutamate by Enzymatic Hydrolyses

The simple method to prepare the β-cycloalkyl aspartate and γ-cycloalkyl glutamate by enzymatic reactions has been developed. Compared with conventional chemical methods, the enzymatic method is more facile.     

Proton nuclear magnetic resonance spectra of brain tumors

Proton nuclear magnetic resonance (NMR) spectra were successfully measured in human brain tumor tissues and experimental rat brain tumors. The investigation was performed on clinical materials which consisted of tissue from one normal brain and 36 brain tumors. Normal rat brain tissue and rat glioma implanted in the brain were also analysed. NMR measurements were carried out at the resonance frequency of 99.54 MHz. The proton NMR spectrum of the normal brain consisted of one broad component and eight superimposed sharp peaks. The sharp peaks obtained from the brain tumors varied from those of the normal brain. A decrease in the signal intensity from N-acetyl aspartate was the most common finding in all tumors. Spectral patterns were similar within the same histological types, but varied among the different types. Therefore, ¹H-NMR spectra might indicate the metabolism characteristic of each tumor type which would be invaluable for clinical differential dagnosis of brain tumors.     

Synthesis of optically active β-alkyl aspartate via [3,3] sigmatropic rearrangement of α-acyloxytrialkylsilane

The synthesis of four types of optically active β-carbon-substituted analogs of threo-β-hydroxy aspartate (THA) and a β-carbon-substituted analog of threo-β-benzyloxy aspartate (TBOA), which are potent blockers of excitatory amino acid transporters in the mammalian central nervous system, via the chirality-transferring ester-enolate Claisen rearrangement of α-acyloxytrialkylsilane is described.     

The stir-frying can reduce hepatorenal toxicity of Fructus Tribuli by inactivating β-glucosidase and inhibiting the conversion of furostanol saponins to spirostanol saponins

The purpose of this study was to illustrate the mechanism of “enzyme inactivation and toxicity reduction” of Fructus Tribuli (FT) after being heating processed. Ultra-high performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UHPLC-MS/MS) was used to quantitatively analyze the contents of four steroidal saponins in crude Fructus Tribuli (CFT) and stir-fried Fructus Tribuli (SFT) under different storage times at room temperature. The enzyme activity of β-D-glucosidase in CFT and SFT were determined and calculated by ultraviolet–visible spectrometry (UV-VIS spectrometry). In addition, the enzyme hydrolysates of FOT and tribuluside A were qualitatively analyzed by ultra-high-performance liquid chromatography coupled with quadruple-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). The hepatorenal toxicity of spirostanol saponins in FT were further confirmed by in vivo and in vitro experiment. This study confirmed that “enzyme inactivation and toxicity reduction” was one of the reasons why the stir-frying can reduce hepatorenal toxicity of FT, and further enriched the exploration on the mechanism of processing toxicity reduction.