药学学报最新文献

A pre-column derivatization method combined with UHPLC-MS/MS was developed for thesimultaneous determination of salidroside and tyrosol in Beagle dog plasma. After protein precipitation byacetonitrile, the liquid supernatant was treated with dansyl chloride under dark conditions at 60 ℃ for 30 min,and then, the sample solution was extracted using methyl tertiary butyl ether. The multiple reaction monitoringin positive ion mode was used for MS detection of the tested analytes with the specific ion transitions ofm/z 534.2→372.0 for salidroside derivative, m/z 372.0→171.0 for tyrosol derivative and m/z 506.0→171.0 forarbutin derivative. The chromatograph separation was achieved on an ACQUITY UPLC® BEH C18 column(100 mm × 2.1 mm, 1.7 μm) with a gradient mobile phase consisting of acetonitrile (0.1% formic acid)-water(10% acetonitrile, 0.1% formic acid) for 9 min. The assay showed a good linearity over the range of 0.02/0.1 −20/10 μmol·L−1 with a lower limit of quantitation of 0.02 and 0.1 μmol·L−1 for salidroside and tyrosol in dogplasma, respectively. The intra- and inter-day precisions were all less than 8.68%, and the accuracy was within±11.4%. The established method with a high sensitivity, good specificity and reliability was appropriate forsimultaneous determination of salidroside and tyrosol in dog plasma and successfully applied to a pharmacokineticstudy after intragastric administration of salidroside to Beagle dogs.

Postoperative intra-abdominal adhesion is one of the most common complications in the postoperative period. Current remedies are very ineffective to prevent the pathological outcomes except steroid hormones. Rhynchophylline is deemed as a pharmacologically active component from traditional Oriental medicine Uncaria rhynchophylla (Miq.) Jacks. (Rubiaceae). This study was designed to investigate the preventative effect of rhynchophylline on the abdominal adhesions in rats. Rhynchophylline relieved the experimental abdominal adhesion and decreased the levels of interleukin-1 β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the blood serum in a dose-dependent manner. The levels of transforming growth factor- β1 (TGF-β1) and connective tissue growth factor (CTGF) were reduced significantly in the peritoneal fluid. The potential mechanism of the activity is related to inhibition of the TGF- β1/Smad signaling pathway.

This study was designed to explore the impact of depression on kidney-yang deficiency in rats.Rats were repeatedly injected with hydrocortisone for 21 days to establish the depression model with kidneyyangdeficiency. Tolbutamide, chlorzoxazone, theophylline, midazolam, omeprazole and dextromethorphanwere used as substrates of CYP2C6, CYP2E1, CYP1A2, CYP3A2, CYP2D1, and CYP2D2 to test the depressionimpact on drug metabolism. Plasma concentrations of six CYP450 were determined by LC-MS/MS and used aspharmacokinetic parameters. Consequently, metabolism of theophylline, chlorzoxazone and tolbutamide wereaccelerated significantly in the model relative to the control (P < 0.01), but dextromethorphan, omeprazole andmidazolam did not exhibit a significant difference. The present study suggests that depression with kidneyyangdeficiency had a strong induction of CYP2E1 and moderate induction of CYP1A2, CYP2C6 in the ratmodel.

This study is designed to investigate the protective effect and mechanism of cordycepin on non- alcoholic fatty liver in ob/ob mice. Twelve-week-old male ob/ob mice were divided into 5 groups according to their body weight and blood glucose, and C57BL/6J mice were used in the control group. The animals were orally administered with cordycepin for 7 weeks. Body weight and food intake were measured once a week. Blood were collected from ophthalmic venous and biochemical indexes were determined at the 2nd and 4th week. Insulin tolerance test was performed at the 5th week. After 7 weeks of administration, liver tissues were collected to determine the contents of triglycerides and total cholesterol, and pro-inflammatory cytokines. Liver histology was performed by hematoxylin-eosin and oil-red O staining. Total RNA were extracted from liver tissues and the levels of lipid metabolism-related and inflammation-related genes were detected by real time PCR. Cordycepin effectively reduced the blood lipids level and improved liver function. Nevertheless, it did not improve insulin resistance in ob/ob mice. Cordycepin significantly reduced the contents of triglycerides and cholesterol, and the levels of pro-inflammatory cytokines in liver tissues. Moreover, cordycepin remarkably suppressed the expression of genes related to lipids synthesis and inflammation. These results indicate that cordycepin may improve non-alcoholic fatty liver in ob/ob mice, and the underlying mechanism may be associated with decreased expression of genes related to lipids synthesis and inflammation.

Thiochromanones and 1,3,4-thiadiazoles as heterocyclic compounds have broad biological activities. In order to find novel compounds with antifungal bioactivity, substituted thiophenol and maleic anhydride were used to synthesize the intermediate 4-oxothiochromane-2-carboxylic acid. It was reacted with 2-amino-1,3,4-thiadiazole to get fourteen target compounds containing 1,3,4-thiadiazole moiety. The structures of the obtained compounds were confirmed by 1H NMR, 13C NMR and HR-MS. All compounds were investigated for antifungal activity via microdilution broth method. The results showed that the target compounds 3a and 3c to Epidermophyton floccosum and Mucor racemosus exhibited better antifungal activity than the positive control fluconazole, in which the minimum inhibition concentration can reach 8 μg·mL−1 and 16 μg·mL−1. Compound 3e showed significant inhibitory activity to Helminthosporium maydis, Sclerotinia sclerotiorum and Botrytis cinerea compared with that of the positive control carbendazim. Compound 3b exhibited inhibitory activity to Helminthosporium maydis better than the positive control carbendazim.

In our preliminary studies, we observed zolmitriptan (ZOL) treatment led to induction of CYP3A2 in male not female rats. To figure out the reason is of great significance for drug-drug interactions and personalized administration. Since growth hormone (GH) is known as the major mechanistic determinant of sexually-dimorphic gene expression like CYP3A2 in rat liver, the impacts of ZOL on both plasma GH levels in non monosodium glutamate (MSG)-treated rats and CYP3A2 expression in GH depleted MSG-treated rats were studied. ZOL was shown to partially suppress GH levels in both genders. Furthermore, CYP3A2 protein and mRNA level declined in male not female MSG-treated rats. In order to study the possible molecular events involved in the depression of GH and gender-selective induction on rat CYP3A2 by ZOL, the mRNA and protein level(whole protein and nuclear protein) of hepatocyte nuclear factor 4α (HNF4α) was investigated. Nuclear accumulation of HNF4α was observed in the normal male not female rat liver tissue following ZOL treatment. However, this kind of nuclear translocation did not occur in rat hepatocytes and MSG-treated rats. These findings demonstrated CYP3A2 inducibility by ZOL was gender-selective. GH and HNF4α may play an important role in CYP3A2 induction.

Traditional anti-depressant therapy based on the regulation of monoamine neurotransmitters has shown certain limitations. Recently, accumulating clinical and preclinical studies have reported the tantalizing link between immune dysregulation, inflammatory process and the initiation and exacerbation of major depressive disorder (MDD). With a deepening understanding of neural-immune-metabolic interactions, an immunometabolism driven disease network has attracted huge interests in understanding neuronal inflammation and dysfunction underlying MDD pathogenesis and intervention. This review describes recent data uncovering immunometabolic dysregulation as a key factor in MDD network, with a focus on the recent appreciation of immune-metabolic actions of several anti-depressant compounds. The implications for the discovery of novel antidepressant drugs and clinical management of MDD are discussed.

Precision medicine (PM) involves the application of "omics" analysis and system biology to analyze the cause of disease at the molecular level for targeted treatments of individual patient. Based on the targeted treatment PM is closely related to pharmaceuticals, which, as a therapeutic means and supply front, mainly embody the two aspects: drug discovery/development, and clinical administration. Innovation of new molecular entities with safety and specific efficacy is the prerequisite and guarantee for the PM practice; on the other hand, the outcome and clues in clinical PM feedback to new drug research. PM and drug research/application are interdependent and promote each other. Aimed at precision medicine, drug discovery and development involve well-known contents: the discovery and validation of targets, the association between target functions and indications (proof of concept), lead discovery and optimization, the association between preclinical investigations and clinical trials, the lean of industrialization and pharmacoeconomics. At the molecular level the therapeutic efficacy originates from the interactive binding between specific atoms or groups of the drug molecule and the complementary atoms or groups of the macromolecular target in three-dimensional space. The strict arrangement of such critical atoms, groups, or fragments reflect specific features for a precise binding to the corresponding target. An alteration of amino acid residues in mutational targets leads to the change in conformation of the target protein, and an accurate structure of drug is necessary for binding to the mutant species and avoiding off-targeting effect. For the tailoring of clinical treatment to the individual patient design and development of various new molecular entities are critical for treatment choice according to the molecular features of biological markers of patients. This article provides some examples and methods of drug design and development in the new period.

The genus Tripterygium is an immune suppressor in the Chinese traditional medicines. Due to the habitat destruction and anthropogenic over-exploitation, the wild genus Tripterygium plants have decreased dramatically in recent years or even been endangered. It is critical to evaluate and protect genus Tripterygium wild resource. In this research, simple sequence repeat (SSR) molecular markers were applied to the investigation of the genetic diversity and genetic structure of 28 populations for genus Tripterygium (396 samples from 9 provinces in China). We found a high level of genetic diversity (percentage of polymorphic loci PPL = 77.29%, Shannon’s information index I = 0.639 4; Nei’s expected heterozygosity H = 0.359 9) and high genetic differentiation among the populations (gene flow N_m = 0.228 7). Based on Nei’s genetic distance, the phylogenic tree of populations was constructed and 28 populations were divided into 6 clusters according to STRUCTURE clustering analysis. T. hypoglaucumwas was mainly divided into 3 clusters, including Sichuan, Yunnan and Guizhou- Chongqing. T. regelii was separated to cluster 4, while T. wilfordii was divided into two clusters: the transition type LQ and NY were divided into cluster 5, and the others were in cluster 6. These results provide a theory basis for the conservation of wild resource, research of genetic polymorphism and molecular marker for assisted breeding of genus Tripterygium.

Twenty phenylpropenamide analogs with structural novelty were designed and synthesized upon pharmacophore-combination strategy. The structures of target compounds were elucidated by IR, 1H NMR, 13C NMR and MS, and all the target compounds were biologically evaluated for the inhibitory activities of platelet aggregation induced by adenosine diphoshate（ADP） and（AA） arachidonic acid via Bron method. As a result, compounds 6b, 9b, 9d and 9h demonstrated potent inhibitory activity against platelet aggregation induced by AA. Meanwhile, compounds 6b, 6d, 6j, 9b and 9g exhibited significant suppression of platelet aggregation induced by ADP.