The development of new drug is not only the main driving force for the development of pharmaceutical industry, but also plays a very important role in the social development. However, with the increasing demands, new drug development is facing great difficulties in recent years. The hypothesis of highly selective single-target is meeting the challenges because of its limitations. Network pharmacology has been one of the new strategies for new drug discovery based on single-target drug research in recent years. This paper focused on the basis of network pharmacology and its research progress, discussed its development direction and application prospects, and analyzed its limitations and problems as well. The application of network pharmacology in new drug development is discussed by comparing its guidelines with those of traditional Chinese medicine theory and Effective Components Group hypothesis of Chinese medicines.

The emerging of network pharmacology and polypharmacology forces the scientists to recognize and explore new mechanisms of existing drugs. The drug target prediction can play a key significance on the elucidation of the molecular mechanism of drugs and drug reposition. In this paper, we systematically review the existing approaches to the prediction of biological targets of small molecule based on chemoinformatics, including ligand-based prediction, receptor-based prediction and data mining-based prediction. We also depict the strength of these methods as well as their applications, and put forward their developing direction.

In present study, standard method and standard operation practice for measuring the activities of influenza neuraminidase and its inhibitors have been established. The accuracy and stability of the method has been evaluated. Standard operation is as following: 10 microL sample, 30 microL neuraminidase and 60 microL substrate are added to one well of a 96-well plate, and then incubated at 37 degrees C for 1 h. The reaction was stopped with NaOH before fluorescence intensity determination. One unit of neuraminidase is defined as the amount of enzyme that produces 1 nmol 4-MU in 1 h under above conditions. The inhibition accuracy is indicated by an uncertainty measurement of 6.51 x 10(-12), and its stability was reaffirmed by determination of oseltamivir acid. In this study, systematic assessment of neuraminidase inhibitory assay not only provided theoretical basis of its application in drug discovery, but also made preliminary attempt to use uncertainty measurement as a parameter in biological measurement.

To study in vitro anti-influenza viral activities of Chinese traditional patent medicines for influenza prevention and treatment, neuraminidase (NA) activity assay was used to examine NA inhibitory activity of 33 Chinese traditional patent medicines through fluorimetric assay, and influenza virus induced cytopathic effect (CPE) inhibition assay was used to verify their anti-influenza viral activities in vitro. The assay results showed that most liquid preparations displayed relatively high NA inhibitory activities, such as Shuanghuanglian oral liquid, Qingkailing oral liquid, Qingre Jiedu oral liquid, and Reduning injection. Among liquid preparations, Shuanghuanglian oral liquid not only displayed the highest NA inhibitory effect, but also exhibited obvious in vitro anti-viral activity in CPE experiment. Among solid preparations, Shuanghuanglian powder for injection showed the highest activity on NA inhibition, and Fufang Yuxingcao tablet showed relatively strong anti-influenza viral activity in CPE cells. From the results, it can be concluded that most Chinese traditional patent medicines possessed NA inhibitory activity, but only a few of them displayed significant in vitro anti-influenza viral activities. These results will provide important information for the isolation of active constituents, and for the clinical uses of Chinese traditional patent medicines for influenza treatment and prevention.

In order to improve the efficiency of drug screening on serotonin transporter (SERT) inhibitors, a high-throughput screening (HTS) model is established in RBL-2H3 cells. The RBL-2H3 cells are very similar to the serotonin genetic neuro, in modulation of post-receptor mechanisms and transduction pathway of SERT reactivated. Depending on a fluorescence substrate ASP+ used in detection method of inhibitor rates, it's convenient, quick, accurate and effective, not making the environmental biohazard compared with radioactive experiments. Furthermore, biological screening model combined with computer aided virtual screening technique describing high-throughput virtual screening (HTVS). Bayesian classification method and molecular fingerprint similarity were applied to virtual screening technique, for screening compounds in compound library. Some compounds have been found, and then validated further by biological screening model. Combination of HTS and HTVS improves the efficiency of screening SERT inhibitors.

Objective To investigate the effect of butylphthalide (NBP) on H2S content and the expression of NR2B in the hippocampus of alcohol dependence rats. Methods A total of 84 SD male rats were randomly divided into 6 groups. Except for the normal group, other groups were subjected to alcohol solution with concentration of 6% ( V/V) for 28 d. Drug intervention began at the 14th day,and rats in the low,medium,high dose group were treated with NBP with a different concentration. Erden abstinence scoring was used to evaluate the rats withdrawal symptom. H2S content was measured in one side of hippocampus and CBS activity was tested in the other side of hippocampus. Hippocampus of 3 rats from each group was used to investigate NR2B mRNA level. Results Withdrawal symptom score ( 12.27 ± 1. 19),H2S content(30. 25 ±8.82), CBS activity (72. 44 ±7. 46) and NR2B mRNA expression( 19. 47 ±0. 86) in medium dose NBP group rats were lower than withdrawal symptom score(14.09 ±2.21) ,H2S content(44. 50 ±6. 65) , CBS activity(79. 06 ±4. 57) and NR2B mRNA expression (29. 13 ±1.39) in experimental control group (P<0.05). Withdrawal symptom score(12. 18 ±1.08) ,H2S content(33.00 ±5.38) ,CBS activity(67. 81 ±9. 37) and NR2B mRNA expression(23. 12 ± 1. 86) in high dose NBP group rats were lower than experimental control group (P < 0. 05). Conclusion NBP can reduce withdrawal symptoms of alcohol dependence rats,may be related to decreased expression of H2S/CBS system, and NR2B mRNA expression.

ObjectiveTo observe the effect of alcohol exposure during pregnancy on learning and memory and content of hydrogen sulfide(H2S) in the hippocampus of infant rats.MethodsThe animal models of alcohol exposure during pregnancy were made,and the learning and memory were evaluated by Y-maze in adult offspring.Content of H2S and activity of cystathionine-beta-synthase(GBS) in the hippocampus of the brain were evaluated with spectrophotometry;and CBS protein expression in the hippocampus was detected by immunohistochemistry.ResultsThe learning and memory ( (43.00 ± 15.33 ) times) of alcohol exposure during pregnancy group was significantly decreased compared with that of control and drinking groups (( 25.13 ± 12.35 )times and (26.12 ±11.95 ) times,P ＜ 0.05 ) ; spectrophotometry results showed that the content of H2S ( ( 30.32 ± 5.84 ) nmoL/g) of alcohol exposure during pregnancy group was significantly increased compared with that of control ( ( 52.51 ±7.85 ) nmol/g) and drinking groups( (49.93 ± 4.29 ) nmol/g),and the activity of CBS( ( 55.13 ± 4.45 ) nmol/g)of alcohol exposure during pregnancy group was significantly increased (P ＜ 0.01 ) compared with that of control ( (71.06 ± 5.58 ) nmol/g) and drinking groups( (69.96 ± 6.13 ) nmol/g) ; immunohistochemistry showed that the expressionof CBSproteinofalcoholexposureduringpregnancygroupwassignificantlyincreased.ConclusionThe damage effect of alcohol exposure during pregnancy on nerve system of infant rats may interrelate with down-regulation of H2S/CBS in the hippocampus.

AIM:In order to investigate the molecular mechanism of alcoholism acting on learning and memory,the dysfunction of learning and memory function was observed and the content of nitric oxide(NO)and neuronal nitric oxide synthase(nNOS)were determined in rats with acute alcoholism.METHODS:The mature male Sprague-Dawley rats were randomly divided into two groups.The experimental group animals were intraperitoneally administered with ethanol.The control group animals were injected with saline in the same way.The tests of learning and memory were performed at Y-maze after 6 h.Then brains were removed and the content of NO in brain tissue and nNOS expression in hippocampus CA1,corpus striatum were determined,respectively.RESULTS:(1)The training times to reach qualifying standards of Y-maze in experimental group(34.33?13.04)were higher than those in control group(27.50?8.79,P

Objective To observe the changes of N-methyl-D-aspartate (NMDA) receptor 2B subunit (NR2B) expression in the striatum of chronic alcohol exposured rats at different withdrawal time.Methods 72 male Wistar rats were randomly divided into withdrawal 2h group,withdrawal 6h group,withdrawal 12h group,withdrawal 1d group,withdrawal 3d group and control group,and 12 rats in each group.In the 5 withdrawal groups,ethanol was administered in drinking water at the concentration of 6％ (V/V) for 16 weeks,and rats in control group were maintained with water.After 16 weeks ethanol was removed and ethanol withdrawal syndromes were evaluated.The expression of NR2B protein in the striatum was measured by immunofluorescence and western blot and the expression of NR2B mRNA in the striatum was measured by realtime PCR.Results Compared with withdrawal scores of control group((1.50±0.80)),scores of withdrawal 2h,6h,12h,1d,3d groups ((10.42±2.50),(15.42± 1.93),(9.25±2.01),(7.67± 1.92),(2.25±0.87) respectively) were higher,and the withdrawal scores of withdrawal 6h group were the highest.Compared with the expression of NR2B fluorescence intensity (2210.00± 178.20),the expression of NR2B protein(0.150±0.009) and the expression of NR2B mRNA(0.006±0.001) in the striatum of control group,the expression of NR2B fluorescence intensity (2710.56 ± 194.21),(5035.16 ± 234.41),(3326.23 ± 378.16),(2570.64 ±177.88),the expression of NR2B protein (0.192±0.008),(1.649±0.205),(0.783±0.109),(0.180±0.009) and the expression of NR2B mRNA (0.026±0.002),(0.351±0.034),(0.248± 0.023),(0.024±0.003) of withdrawal 2h,6h,12h,ld groups were significantly higher (P＜0.05),and with the extension of the withdrawal time,the expression was gradually increased.The expression of withdrawal 6h group was the highest,then began to decline,and returned to baseline levels at withdrawal 3 d(P＞0.05).Withdrawal scores were positively correlated with the expression of NR2B protein(r=0.719,P＜0.01),the expression of NR2B protein was positively correlated with the expression of NR2B mRNA(r=0.937,P＜0.01),and the expression of NR2B mRNA was positively correlated with withdrawal scores(r=0.673,P＜0.01).Conclusion The expression of NR2B was up-regulated in the striatum of chronic alcohol exposured rats at different withdrawl time.NR2B protein and NR2B mRNA expression is positively correlated with the withdrawal scores,suggesting that regulating the expression of NR2B may be a new target for the treatment of ethanol withdrawal symptoms.

The pharmacokinetic profile of gallocatechin-7-gallate (J10688) was studied in rats after intravenous administration. Male and female Sprague-Dawley (SD) rats received 1, 3, and 10 mg/kg (i.v.) of J10688 and plasma drug concentrations were determined by a high performance liquid chromatography-mass spectrometry (LC-MS) method. The pharmacokinetic software Data Analysis System (Version 3.0) was used to calculate the pharmacokinetic parameters. For different i.v. doses of J10688, the mean peak plasma concentration (C 0) values ranged from 11.26 to 50.82 mg/L, and mean area under the concentration-time curve (AUC0-t ) values ranged from 1.75 to 11.80 (mg·h/L). J10688 lacked dose-dependent pharmacokinetic properties within doses between 1 and 10 mg/kg, based on the power model. The method developed in this study was sensitive, precise, and stable. The pharmacokinetic properties of J10688 in SD rats were shown to have rapid distribution and clearance values. These pharmacokinetic results may contribute to an improved understanding of the pharmacological actions of J10688.