Multi-target drugs can simultaneously adjust multiple links of the disease network. Despite the higher efficacy and lower toxicity caused by single targets, multi-target drugs become ideal drugs for treating complicated diseases as well the main direction of drug R & D. By virtue of their structural diversity, higher multi-target activity and lower toxicity, natural products become an important source for developing multi-target drugs. Computer-aided drug design (CADD) is a commonly used multi-target drug R&D method, which mainly includes virtual screening and pharmacophore design. In this paper, the authors made a systematical analysis and discussed the prospects and advantages of various methods for multi-target drug R&D with natural products.
Biological Products ; chemical synthesis ; pharmacology ; Biomedical Research ; instrumentation ; Computer-Aided Design ; Drug Design ; Humans ; Molecular Targeted Therapy

AIM:To investigate the effect of cyclopamine , a Hedgehog ( Hh) signaling pathway inhibitor , on the biological behavior of intrahepatic cholangiocarcinoma cell line RBE .METHODS:The proliferation of RBE cells was detected by cell counting with Typan blue staining and MTT assay , and the apoptosis was analyzed by the flow cytometry . The Transwell invasive cabin assay was used to detect the invasion ability , and Western blot was used to determine the pro-tein expression of Gli 1 and MMP-9 in the RBE cells before and after cyclopamine treatment .RESULTS:Cyclopamine in-hibited the growth of RBE cells in a time-and dose-dependent manner .After cyclopamine treatment for 24 h, 48 h and 72 h, the apoptotic rates were significantly higher than those in control group .In control group , the number of cells invading through the Matrigel of invasion chamber was 154.52 ±13.61, while in experimental group it was 62.00 ±12.17, indica-ting that the invasion ability of the cells declined significantly .Furthermore , Western blot showed that the protein levels of Glil and MMP-9 in the RBE cells were decreased after treatment with cyclopamine for 24 h and 48 h.CONCLUSION:Blockage of the Hh signaling pathway with cyclopamine suppresses the proliferation , promotes the apoptosis and inhibits the invasion ability of RBE cells .

To study the quantitative structure-activity relationship (QSAR) between the stuctures of 29 flavonoids and the inhibitory activity of their multidrug resistance-associated protein (MRP) 1 and 2 by using the comparative molecular similarity index analysis (CoMSIA). By studying the impact of the combination of different molecular force fields, researchers obtained the molecular force fields that played an important role in inhibiting the activity of MRP1 and MRP2, built the optimized QSAR model, and discussed the structural modification method for flavonoids' multidrug resistance-associated protein inhibitor. The results of the study could not only provide the guidance for new drug R&D, but also help partially discuss the synergy mechanism between MRP1 and MRP2 receptors and traditional Chinese medicines containing flavonoids.
Drugs, Chinese Herbal ; chemistry ; pharmacology ; Flavonoids ; chemistry ; pharmacology ; Humans ; Models, Molecular ; Multidrug Resistance-Associated Proteins ; antagonists & inhibitors ; chemistry ; Quantitative Structure-Activity Relationship

OBJECTIVEMedicinal properties are the basic attribute of traditional Chinese medicines (TCM), while the medicinal property theory is the core theoretical foundation of TCM formula combination. In this particle, authors studied the characteristics of pharmacological effects of property combination of traditional Chinese medicines distributing along meridians, with the aim to introduce the medicinal property combination regularity into the design and optimization process of compound TCMs, and bring the medicinal property theory into full play in guiding the formula combination.

METHODIn this paper, TCMs distributing along "the lung meridian" was taken for example. The medicinal property combinations of TCMs distributing along "the lung meridian" recorded in Pharmacopeia (2010) was collected and processed. Besides, Chinese journal full-text database (CNKI) was used to collect all of pharmacological study literatures concerning the above TCMs that have been published since 1980. The pharmacological information was also supplemented by reference to Science of Chinese Materia Medica and Clinical Science of Chinese Materia Medica.

RESULTTCMs distributing along the lung meridian with different properties and tastes showed significant differences in pharmacological effects. For example, mild-sweet-lung medicines could lower blood sugar levels, decrease anoxia and enhance immunity; Mild-bitter-lung medicines showed anti-bacterial, anti-hypertension, anti-oxidation effects; Hot-sweet-lung medicines showed antibechic and anti-bacterial effects. And Hot-bitter-lung medicines showed phlegm eliminating and anti-inflammatory effects. Meanwhile, TCMs distributing along the lung meridian had similar pharmacological characteristics, such as anti-bacterial and anti-inflammatory effects, which is consistent with lung's feature in susceptibility to exogenous pathogenic factors.

CONCLUSIONIn this study, authors discovered pharmacological characteristics of different TCMs distributing along the lung meridian, which links TCM theory with modern study achievements and lays a foundation for establishing a TCM property formula combination system.

Databases, Factual ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Humans ; Lung ; drug effects ; Lung Diseases ; drug therapy ; Meridians

Studies on the prescription combination regularity based on medicinal tastes focus on the internal relations between the structure and hierarchy of the prescription combination system. In this paper, with the systematic and scientific self-similarity theory as the core ideology, authors systematically interpreted the self-similarity theory of medicinal properties, defined the self-similarity of prescriptions with identical or similar medicinal properties, and built the systematic view of medicinal property theory based on the prescription combination based on the entity grammar system. As a result, the system was conducive to integrating traditional Chinese medicinal knowledge of syndromes, therapeutic principles, efficacies, medicinal properties and tastes and achieving the automatic design and optimization process from symptoms to prescriptions, and providing scientific and feasible methods and technical systems for the application of the medicinal property theory, with a guiding significance to the technology, methodology and theory of decoction pieces compatibility, component compatibility and compound medicine design.
Drug Combinations ; Drug Prescriptions ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Humans ; Medicine, Chinese Traditional

This article was aimed to study the factors associated with sleep quality of anger-out and anger-in population based on the frequent pattern-tree (FP-Tree) growing algorithm with data mining. The algorithm of structuring frequent model FP-tree and mining frequent itemsets were designed. The database information scanned was recorded by using FP-Tree growing algorithm through state-trees. The frequent itemsets met minimum support required was generated through reducing the search space of project sets and scanning database only one. The data mining of all factors associated with emotional diseases was actualized. The results showed that factors associated with sleep quality of anger-out and anger-in population were disturbance in respiration, cough or snoring, feeling cold, hot or nightmares. The total time for program analysis was 2 seconds. It was concluded that data mining algorithm based on FP-Tree frequent itemsets can effectively realize the useful information receiving from factors associated with emotional diseases.

The combination of medicinal properties refers to expression forms of elements with active properties combined according to a specific sequence. The mode of medicinal property combination refers to the compatible relationship multiple medicinal property combinations. In this paper, based on the mode, safflower, Taohong Siwu decoction, Xuefu Zhuyu decoction and Buyang Huanwu decoction were taken for example to study the characteristics of the compatibility among single herb, herbal pairs and prescriptions. The authors discovered the similarities and differences among them, interpreted the self-similarity in medicinal property combinations of traditional Chinese medicines, and analyzed the compatible relationship among multiple medicinal property combinations, so as to bring forth new ideas in discovering the correlation between the compatibility study mode of traditional Chinese medicines based medicinal property combinations and the efficient compatibility of medicinal property combination.
Drug Combinations ; Drug Prescriptions ; Drug Therapy ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Humans ; Medicine, Chinese Traditional

ObjectiveTo study the characteristics in negative energy balance in different-aged patients with metabolic syndrome (MS) and come out with nursing countermeasures.Methods Twenty-four hour dietary data reviewing and the international physical activity questionnaire were used to investigate energy intake and consumption among 384 MS patients.The fat content,fat percentage and lean body mass were measured by the human body composition analyzer.Body mass index (BMI),waist/height,fat percentage,lean body mass,energy intake and energy consumption were compared between different ages and sexes.Results In the group aged over 51 years,the waist/height of female MS patients was significantly smaller than their male counterparts (P<0.05).For all groups of different ages,the percentage of fat in the female patients was significantly larger,their lean body mass was less(P<0.01), their intake of energy was significantly lower than that of the males (P<0.05).The intake of energy among the male patients at the group aged 21~30was significantly larger than the males of other age groups and so it was with the energy intake of the males aged 21-70 years as compared to the males aged 71~80 years (P<0.05).Conclusion Education on disease knowledge should be strengthened among healthy people so as to realize the negative energy balance based on the rate of waist/height,body composition,energy intake and energy consumption,which is of great significance for the prevention and control of metabolic syndromes.

In order to explore reasonable artificial cultivation pattern of Thesium chinense, the biological characteristics and nutrients change in the process of winter dormancy of T. chinense was studied. The phenological period of T. chinense was observed by using fixed-point notation and the starch grains changes were determined dynamically by PAS-vanadium iron hematoxylin staixjing method. Soluble sugar and starch content were measured by anthrone-sulfuric acid method and amylase activity was determined by DN'S method. The results showed that the normal life cycle of T. chinense was two years. T. chinense was growing by seed in the first year, but growing by the root neck bud in the second year. During the process of dormancy, starch and soluble sugar could mutual transformation in different periods. T. chinense had sufficient carbohydrate to maintain growth and also a lot of small molecules to improve their ability to fight against adversity.
Plant Dormancy ; Plant Leaves ; chemistry ; growth & development ; metabolism ; Plant Roots ; chemistry ; growth & development ; metabolism ; Plant Stems ; chemistry ; growth & development ; metabolism ; Santalaceae ; chemistry ; growth & development ; metabolism ; Seasons ; Starch ; analysis ; metabolism

OBJECTIVETo investigate the effects of chronic aluminum exposure on the learning and memory abilities and brain-derived nerve growth factor (BDNF) in Sprague-Dawley (SD) rats.

METHODSThirty-two male SD rats were randomly and equally divided into 4 groups: control group and high-, middle-, and low-dose exposure groups. The rats in high-, middle-, and low-dose exposure groups were fed with the feed mixed with AlCl(3) (120.0, 12.0, and 1.2 mg/kg, respectively), while the rats in control group were fed conventionally. After 6 months of feeding, brain aluminum levels were determined by inductively coupled plasma mass spectrometry; Morris water maze was employed to test the learning and memory abilities; the expression and content of BDNF in brain tissue were measured by Western blot and enzyme-linked immuno sorbent assay (ELISA).

RESULTSThe high- and middle-dose exposure groups had significantly higher brain aluminum levels than the control group (P<0.05). The Morris water maze test showed that the high- and middle-dose exposure groups had significantly prolonged escape latency (P<0.05), significantly prolonged time taken to first reach the target quadrant (P<0.01), and significantly decreased number of platform crossings and time spent in the target quadrant (P<0.05), as compared with the control group. The Western blot and ELISA showed that the expression and content of BDNF in brain tissue decreased as the dose of AlCl(3) increased, and they were significantly lower in the high- and middle-dose exposure groups than in the control group (P<0.05).

CONCLUSIONChronic aluminum exposure (12.0 and 120.0 mg/kg) can lead to cognitive dysfunction in rats, and the decreased expression of BDNF may be one of the mechanisms of learning and memory deficits induced by aluminum.

Aluminum ; toxicity ; Animals ; Brain ; metabolism ; Brain-Derived Neurotrophic Factor ; metabolism ; Male ; Maze Learning ; drug effects ; Rats ; Rats, Sprague-Dawley ; Toxicity Tests, Chronic