药学学报最新文献

Research of plant development and metabolism has drawn lots of attention with the fast developmentof science of mycorrhizal biology, molecular biology and metabonomics technology. It has become one ofhot fields in the study of endophytes and plant, which would affect plant ’s metabolite composition. This wouldprovide opportunity for appraising and modifying traits to medicinal plant, and would also perfect the tranditionalstandpoint on forming reason of medicinal plant genuineness. Here we provide a review of theory andmechanism, research and application of interaction between plant and endophyte. This review may enhanceunderstanding of medicinal plant, and evaluating the quality of herbs in production.

In this study, 1-(3-(4-chlorophenyl)-5-methylthio-1H-1,2,4-triazol-1-yl)-butan-1-one discoveredpreviously in our lab was selected as a inhibitor of human dihydroorotate dehydrogenase ( HsDHODH) forstructural optimization. The co-crystal of HsDHODH with the hit was obtained and analyzed for guidingthe subsequent structural optimization. As a result, a series of novel triazole derivatives were designed andsynthesized as potent HsDHODH inhibitors. Among them, compound (3-(4-chlorophenyl)-5-ethylthio-1H-1,2,4-triazol-1-yl)-furan-2-yl-methanone displayed high potency in the inhibition of HsDHODH with an IC50value of 1.50 μmol·L−1. Meanwhile, the structure-activity relationships were analyzed based on the biologicaldata and the co-crystal structure. These results provide a valuable reference for optimization of 1H-1,2,4-triazole derivatives as HsDHODH inhibitors in the future.

Abelmoschus manihot (L.) Medic., a folk herbal medicine in China, is a flowering plant belongingto Abelmoschus L. genus and Malvaceae family, which has been reported with an antidepressant activity. Thestudy was designed to isolate flavonoids from Abelmoschus manihot corolla and explore the action mechanismof antidepressant activities. The flavonoids were isolated and purified by D101 macroporous resin column,polyamide column and Sephadex LH-20 sequentially and identified as myricetin-3-O-β-D-glucoside (1),gossypetin-8-O-β-D-glucuronide (2, G-8-G), gossypetin-3'-O-β-D-glucoside (3), quercetin-3'-glucoside (4, Q-3-G),isoquercitrin (5, IQT), hyperoside (6, HY), myricetin (7), quercetin (8, QT). Compounds 2, 4, 5, 6 and 8(15, 30 and 60 mg·kg−1) were orally administered to mice and the reaction was observed in tail suspensiontest (TST) and forced swimming test (FST). Western blot analysis was used in determination of the proteinexpressions of brain-derived neurotrophic factor (BDNF), tyrosine receptor kinase B (TrkB) and phosphorylationeukaryotic elongation factor 2 (p-eEF2). The results revealed that only Q-3-G and G-8-G (15, 30, 60 mg ·kg−1)significantly reduced the immobility time in FST and TST. Furthermore, Q-3-G and G-8-G remarkably increasedthe expression of BDNF and TrkB, and decreased the expression of p-eEF2. These results suggest thatQ-3-G and G-8-G had an obvious antidepressant activity via up-regulation of BDNF expression. Thenew observation will provide a new direction in the development of antidepressant in the treatment of major depressivedisorder (MDD).

This study was designed to analyze the change of metabolites in the PC12 cells and its mediuminduced by corticosterone (CORT) and glutamate (Glu) by proton nuclear magnetic resonance ( 1H NMR)metabolomics. The multivariate statistical analysis was employed to identify the difference between controlgroups and induced groups, respectively. In addition, metabolite pathway analysis was performed to explorethe characteristic of CORT-induced and or Glu-induced PC12 cells depression model, and to provide thereferences for the selection of in vitro depression models as well as the further understanding of the mechanismon depressive disorders. We found 36 differential metabolites in CORT-induced PC12 cells and medium and42 in Glu-induced PC12 cells. Furthermore, correlation analysis results show that serine and 2-oxoisoleucinewere associated with most differential metabolites in CORT-induced PC12 cells. Lactate and glutathionewere significantly correlated to the vast majority of differential metabolites in Glu-induced PC12 cells. Wespeculated that CORT-induced PC12 cell models may affect the fatty acid metabolism and cell membranestructure, and Glu-induced PC12 cell models may have a difference in the glycolysis and antioxidants.

This study was designed to reverse multidrug resistance of lung cancer cells by downregulating MDR1 genes through RNA interference (RNAi) technology. A novel biodegradable cationic polymer (PEG- b- PLG-g-PEIs, GGI) was synthesized and characterized by 1H NMR. The particle size and zeta potential were measured by dynamic light scattering (DLS). The cell viability profile of GGI was tested by MTT method with both A549 and A549/DDP cell lines. Flow cytometry (FCM) technology was used to investigate the efficiency and intensity of delivering siRNA to cells by GGI polymer. RT-PCR and Western blot were used to detect the mRNA and P-gp expression after GGI/MDR1 siRNA transfection assay. The sensitivity of cisplatin administration after transfecting GGI/MDR1 siRNA polyplexs was performed with MTT and Annexin V-FITC/PI methods. The results suggest that the particle size and zeta potential of GGI/siRNA were 150 −200 nm and 16−28 mV. GGI exhibited a lower cell cytotoxity than PEI 25K and higher efficiency of delivering siRNA, which dramatically decreased the expression of MDR1 mRNA and P-gp of A549/DDP cells and increased much sensitivity to cisplatin in A549/DDP cells. GGI holds a great potential in gene delivery as a novel cationic polymer for further investigation.

Five cassane diterpenes were isolated from the 95% ethanol extract of the seeds of Caesalpiniabonduc (Leguminosea) by a combination of various chromatographic methods, including silica gel, SephadexLH-20, and semi-preparative HPLC. On the basis of spectroscopic techniques, their structures were identifiedas 3β-acetoxy-cassa-12,14(17),15-trien-7β-ol (1), caesalmin C (2), caesall E (3), caesalpinin MJ (4), and1-deacetylcaesalmin C (5). Among them, compound 1 is a new compound and 2, 4, 5 were isolated from theplant for the first time.

It has been an active approach to screen the active ingredients in traditional Chinese medicines(TCMs) according to the affinity property between small molecule compounds and biomaterials such as cells,bacteria and proteins. On the other hand, the biomaterials can be immobilized on a solid support before thescreening procedure. The immobilization method not only can maintain the biological activities of biomaterials,but also have other advantages such as high efficiency, simple operation, easy to be continuous and automatic, etc.Carrier materials (solid supports) for the immobilization including silica gel, magnetic materials, hollow fiber,and the surface plasma resonance sensor chips have been used to immobilize biomaterials and successfullyapplied in the screening of active ingredients from TCMs. In this paper, applications of immobilizationtechniques in the screening of active components from TCMs were reviewed to provide a scientific referenceto the future applications.

The development of pharmaceuticals has been providing many kinds of novel drug deliverysystems, which are important for improving therapeutic effect and one of the most important fields in pharmaceutics.According to their application, we can generally divide the novel drug delivery systems into three categories:quickly performed drug delivery system, long-term drug delivery system and high effective drug delivery system.Some diseases, such as asthma, angina pectoris and migraine, require therapeutics urgently, and the drugs have tobe absorbed in several minutes. Therefore, quickly performed drug delivery systems are developed, such as oraldisintegrating tablets and nasal spray. For normal tablets and capsules, especially the drugs with short bloodhalf life, the drug concentration in blood shows obvious peak-valley phenomenon, which reduces the therapeuticeffect and requires multiple administration. To solve this problem, sustained drug release system was developed,which could release the drugs slowly and sustainably even in zero-order kinetics. The pulse drug delivery systemwas developed that can delayed and pulsed release drug for one or several times. This system is especiallyuseful in the management of asthma and heart disease, which are often found in midnight or early morning whenpatients are in bed. Transdermal drug delivery system could release drugs sustainably and deliver the drugsthrough skin to blood circulation, providing long term activity. The water-insoluble drugs are difficult forpharmaceutical development, thus many methods were developed to improve the solubility and bioavailability ofdrugs. Although biopharmaceuticals are important for disease treatment, the application shadows by the poorstability and low bioavailability. Thus the biopharmaceutical delivery system was developed, which mainlyfocused on structure modification and encapsulation by carriers. Considering therapeutic effect requiresinteraction between drugs and their targets, it is important to deliver drugs to their targets. Therefore, targetingdelivery systems were developed, which mainly based on the nanoparticles. Furthermore, on-demand releasedrug delivery systems are also developed with the property of environment-triggered drug release. In conclusion,the novel drug delivery systems were reviewed in this study.

This study investigates the effects of metoprolol (METO) or/and pravastatin (PRAV) on thepharmacokinetics of metformin (METF) in rats. Twenty-eight male SD rats were divided into METF group,METF+METO group, METF+PRAV group and METF+METO+PRAV group. Blood samples were collectedat 10, 20, 40, 60, 90, 120, 180, 240, 360, 480 and 600 min after oral administration of metformin, andconcentration of metformin in plasma was determined by HPLC. Compared to the METF group, Cmax ofmetformin was significantly decreased (P < 0.01) and MRT0−t , t1/2 and V were significantly increased inthe METF+METO group; t1/2 was significantly decreased in the METF+PRAV group; Cmax was significantlydecreased and MRT0−t was significantly increased in the METF+METO+PRAV group. Compared to theMETF+METO group, MRT0−t of metformin was significantly decreased in the METF+METO+PRAV group.Compared to the METF+PRAV group, Cmax of metformin was significantly decreased (P < 0.01), andMRT0−t , t1/2 and V were significantly increased in the METF+METO+PRAV group. There exist multipledrug interactions of metformin, metoprolol and pravastatin in rats.