药学学报最新文献

The pharmacological activities of natural glycosides are closely related to the polyfunctionalsugar moieties. Modification of active natural products by glycosylation can change the stereochemicalconfiguration, improve the solubility, tune up the activities and change pharmacokinetic properties for higherefficacy and better selectivity. Compared with the common D-glucose, D-allose, a C-3 epimer of D-glucoserarely exists in nature, but it plays an important role in food, health, medicine, and so on. It is not easilymetabolized in the living organisms, but can be used as a safe and low-calorie sweetener. The naturalallopyranosides are absolute conjugation forms which are same as other glucopyranosides and rhamnopyranosideswith a broad array of biological activities. This article summarizes the major progresses made inphytochemistry and biological activity studies of these compounds. Structure-activity relationship analyses ofpartial anti-tumor and anti-diabetic allopyranosides were performed regarding the data reported in the literatures.These insights may provide a theoretical and experimental reference for the discovery of new drug and drugdesign based on allopyranosides.

This study was designed to investigate triterpenoids from the roots of Rosa laevigata Michx.The silica gel column chromatography was used to separate the chemical constituents from the roots of Rosalaevigata Michx. HPLC was used to analyze its purity and chemical constitution. Spectroscopy methods wereused to determine their structures. Five constituents were isolated and identified as19α-OH-3β-E-feruloyl corosolicacid (1), 23-hydroxy-tormentic acid (2), 2α, 3β, 19α, 23- tetrahydroxy-12-en-28-oleanolic acid (3), 2α, 3α, 20β-trihydroxyurs-13 (18)-en-28-oic-acid (4), 2α, 3β, 20β-trihydroxyurs-13 (18)-en-28-oic-acid (5). Compound 1 wasassigned as a new compound, compounds 4, 5 were obtained from the genus Rosa for the first time.

Human chorionic gonadotrophin (hCG), a glycohormone widely used in treatment of infertility,is a heterodimer composed of an alpha- and a beta-subunit. The heterodimer could be dissociated duringproduction and storage with an impact on its bioactivity. A CE-SDS method for quantitative analysis of hCGsubunit dissociation was established in this study by optimization of a variety of method conditions includingsample preparation buffer compositions, incubation temperature, separation voltage, and capillary temperature.This method was validated for good sensitivity, linearity, precision, and accuracy for both α- and β-subunit.CE-SDS also showed much better precision and accuracy than SDS-PAGE. The method was successfully usedin both recombinant hCG (r-hCG) produced by cell culture and hCG (u-hCG) derived from urine. The CE-SDSmethod was used in the study of hCG development and stability. Therefore, it is an useful tool for the qualitycontrol of hCG.

This study was designed to explore the effect of apigenin (Api) on dendritic cell (DCs) maturationand function in murine spleen cells. The single spleen cell was isolated, and then cultured with lipopolysaccharide(LPS) in the present and absence of apigenin. After 24 h, the toxicity of Api and the T cell proliferation weredetermined by CCK8 kit. In addition, we collected the cell-free supernatants to measure cytokine productionusing ELISA, collected the cells to determine the DC maturation using flow cytometry. Finally, we purifiedApi and/or LPS-treated CD11c+ DCs which were pulsed with ovalbumin (OVA)323−339 and then were adoptivetransferred into C57BL/6 mice to detect the OVA323−339-specific T cell proliferation and T helper (Th1) and Th2cell secreting IFN-γ and IL-4 production, respectively. We found that Api did not affect splenocyte viability, butinhibited the production of pro-inflammatory cytokine IL-1β, IL-6 and TNF-α, not anti-inflammatory cytokineIL-10. In addition, Api inhibited the expression of co-stimulatory CD80, CD86 and MHCII of CD11c + DCs.Finally, compared to LPS+OVA DCs group, DCs from Api and LPS co-treated splenocytes (Api+LPS+DCs)impaired OVA323−339-specific T cell proliferation and the production of IFN-γ and IL-4 in CD4+ T cells, whichhad the similar responses with OVA+DCs. These data suggest that Api exhibits anti-inflammatory propertiesvia inhibiting DC activation and function, as a new immune-modulator, which may induce immune-tolerancewith a benefit to those with chronic inflammation.

A new method was developed for the chromatographic fingerprint analysis of Toosendan Fructusby HPLC coupled with the charged aerosol detector (CAD) in the present study. Samples were well separatedon an Agilent ZOBAX SB C18 column (4.6 mm × 250 mm, 5 μm) by gradient elution using acetonitrile and watercontaining 0.1 % formic acid (v/v) at the flow rate of 1.0 mL·min−1. The column temperature was 30 ℃ and theinjection volume was 5 μL. The nitrogen inlet pressure of the charged aerosol detector (CAD) was 35 psi, andthe nebulizer chamber temperature was 35 ℃. In addition, the method of the chromatographic fingerprintscombined with multivariate statistical analysis was effective and reasonable lead to an accurate classification of20 batches of samples from different locations. The results showed that 28 common peaks were observed in thefingerprint and the samples were classified into three clusters. The established method was well validated, andshowed high precision, good repeatability, and satisfactory stability. It may serve in the quality control andevaluation of Toosendan Fructus.

With the method of fluorescence polarization (FP), we screened small molecule inhibitors forPLK1 PBD to identify the lead compounds for antitumor drugs. FP led to the identification of a potent hit,F083-0063, whose inhibition rate was (99.7 ± 0.4) % at 10 μg·mL−1. The IC50 was calculated to be 1.9 ± 0.1μmol·L−1 using Graphpad Prism 5. The effect of the compound on cells' multiplication was measured by MTTassay which showed that F083-0063 inhibited the proliferation of many tumor cell lines. Flow cytometryanalysis indicated that the F083-0063 promoted cell apoptosis and induced cell G2/M arrest. Migration abilitiesof cells, evaluated using scratch test, increased significantly in the presence of F083-0063 with the migration rateas low as (37.6 ± 0.7) % at 20 μmol·L−1. Molecular linkage technique found F083-0063 had good affinity withPLK1 PBD. The results of Western blotting showed that the expression of cyclin-dependent proteins wasincreased after treatment with F083-0063. In summary, F083-0063 has an antitumor activity and is expectedto be an antitumor lead compound targeting PLK1 PBD.

Donafenib is the deuterium derivative of sorafenib, and is an anti-tumor drug in clinical trials. An accurate and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of donafenib and its N-oxide metabolite in human plasma. The analytes and internal standards (sorafenib and sorafenib N-oxide) were extracted from plasma by protein precipitation with acetonitrile, and separated on a Gemini C18 (50 mm × 2.0 mm, 5 μm) column using a gradient elution procedure. The mobile phase consisted of acetonitrile and 5 mmol ·L−1 ammonium acetate (0.2% formic acid) at a flow rate of 0.7 mL·min−1. The total run time was 5.0 min. Positive electrospray ionization was performed using multiple reaction monitoring (MRM) with transitions of m/z 468.2 → 273.2 for donafenib and m/z 465.2 → 270.2 for its internal standard sorafenib, m/z 484.2 → 289.2 for donafenib N-oxide and m/z 481.2 → 286.2 for its internal standard sorafenib N-oxide. The standard curves were linear in the range of 5.00−5 000 ng·mL−1 for donafenib, and 1.00−1 000 ng·mL−1 for donafenib N-oxide. The method was validated and successfully applied to the pharmacokinetics study of donafenib tosylate tablets in volunteers.

D-galactose (D-gal)-induced aging model is widely used in the study of the pharmacodynamics ofantiaging drugs. The model has a shorter life-span, disorders in learning and memory, reduced immune functionand other aging characteristics. Regular and quantitative injection of D-gal solution to rats can producesymptoms of natural aging models that are used in screening of antiaging drugs, and their pharmacologicalactivities. This paper provides a summary of the mechanism of rat model induced with D-gal solution. Themethods of building and evaluation of the aging models are provided. The theoretical basis is included tofacilitate the subsequent research and experiment in the mechanism study of aging and antiaging medicines.

In this study, the endocytosis pathway of heparosan and its intracellular distribution wereinvestigated in MCF-7 tumor cells and COS7 normal cells. The endocytosis inhibition and cellular probelocation experiments showed that MCF-7 tumor cells took heparosan more efficiently and selectively than COS7cells. The cellular uptake of heparosan was energy-dependent in both MCF-7 tumor cells and COS7 normalcells. Moreover, the major endocytosis pathway of heparosan into MCF-7 tumor cells was caveolin-mediatedendocytosis and macropinocytosis. The internalized heparosan was mainly located in lysosomes of the cells.

Population pharmacokinetics is an emerging discipline developed from the combination ofclassical pharmacokinetic compartment model and statistics principles, which has been received more and moreattention in recent years. Population pharmacokinetics plays important roles in all stages of new drug research.In the early preclinical phase, population pharmacokinetic analysis can help to achieve the preliminary predictionof parameters from animal to human, optimize clinical trial designs, and shorten the time required for newdrugs from laboratory to clinical trials. In clinical trials and applications stage, population pharmacokineticresearch can help researchers investigate the related covariates that affecting pharmacokinetic behavior ofpatients comprehensively, and find potential drug-drug interactions in clinical. In addition, populationpharmacokinetics has a unique advantage in pediatric drug development due to its strong analysis ability ofsparse data. This paper provides a summary on the history and methods of population pharmacokinetics,and the application in new drug discovery and development.