Nicotinic acid could increase high density lipoprotein and reduce serum total cholesterol, low density lipoprotein cholesterol and triglycerides in human bodies, thus is frequently applied in treating low high-density lipoprotein cholesterol and hypertriglyceridemia in clinic. However, according to the findings, nicotinic acid could also cause adverse effects, such as skin flush, beside its curative effects. In this study, bioisosterism, fragment-based search and Lipinski's Rule of Five were used to preliminarily screen out potential TCM ingredients that may have similar pharmacological effects with nicotinic acid from Traditional Chinese medicine database (TCMD). Afterwards, homology modeling and flexible docking were used to further screen out potential nicotinic acid receptor agonists. As a result, eleven candidate compounds were derived from eight commonly used traditional Chinese medicines. Specifically, all of the candidate compounds' interaction with nicotinic acid receptor was similar to nicotinic acid, and their docking scores were all higher than that of nicotinic acid, but their druggability remained to be further studied. Some of the eight source traditional Chinese medicines were used to lower lipid according to literature studies, implying that they may show effect through above means. In summary, this study provides basis and reference for extracting new nicotinic acid receptor agonists from traditional Chinese medicines and improving the medication status of hyperlipidemia.
Drug Evaluation, Preclinical ; Drugs, Chinese Herbal ; chemistry ; Humans ; Models, Molecular ; Molecular Structure ; Nicotinic Acids ; chemistry ; Nicotinic Agonists ; chemistry ; Protein Binding ; Receptors, G-Protein-Coupled ; agonists ; chemistry ; Receptors, Nicotinic ; chemistry

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

By using the pharmacophore model of mineralocorticoid receptor antagonists as a starting point, the experiment stud- ies the method of traditional Chinese medicine formula design for anti-hypertensive. Pharmacophore models were generated by 3D-QSAR pharmacophore (Hypogen) program of the DS3.5, based on the training set composed of 33 mineralocorticoid receptor antagonists. The best pharmacophore model consisted of two Hydrogen-bond acceptors, three Hydrophobic and four excluded volumes. Its correlation coefficient of training set and test set, N, and CAI value were 0.9534, 0.6748, 2.878, and 1.119. According to the database screening, 1700 active compounds from 86 source plant were obtained. Because of lacking of available anti-hypertensive medi cation strategy in traditional theory, this article takes advantage of patent retrieval in world traditional medicine patent database, in order to design drug formula. Finally, two formulae was obtained for antihypertensive.
Antihypertensive Agents ; chemistry ; pharmacology ; Databases, Factual ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Medicine, Chinese Traditional ; methods ; Mineralocorticoid Receptor Antagonists ; chemistry ; pharmacology ; Models, Molecular

Aim To investigate the effects of Aplysin on the inhibition of gastric cancer cell in vitro .Methods MTT assay was used to examine the inhibition of gastric cancer cell 1ine SGC-7901 by Aplysin in different concentrations and at different times.The morphologic changes and the apoptosis of SGC-7901 was observed by inverted microscope and Hematoxylin-Eosin(HE)staining.Reverse transcriptase polymerase chain reaction(RT-PCR)assay was used to detect the changes of COX-2 mRNA expressions.Results Aplysin could decrease the proliferation significantly in a dose-dependent manner in SGC-7901 cells.When treating SGC-7901 with Aplysin in concentration of 120, 240 mg·L~(-1) for 24 h, the growth of the cell was obviously inhibited observing by inverted microscope.Aiso, when treating with the same concentration for 18 h, its chromatin became crimpled and breakdown, as well as cell shrinkage and apoptotic bodies formation when using HE staining.The apoptotic rates(%)of SGC-7901 was(15.0±2.12)%, (18.4±2.3)%, respectively, which was significantly higher than(1.4±0.55)% that in control group(P <0.01).60、120、240 mg·L~(-1) Aplysin could not effectively inhibited the mRNA expressions of COX-2(P ＞0.05).Conclusions Aplysin can inhibit the proliferation and induces apoptosis of SGC-7901 cells.

Traditional Chinese medicine (TCM) has definitely clinical effect in treating hyperlipidemia, but the action mechanism still need to be explored. Based on consulting Chinese Pharmacopoeia (2010), all the lipid-lowering Chinese patent medicines were analyzed by associated rules data mining method to explore high frequency herb pairs. The top three couplet medicines with high support degree were Puerariae Lobatae Radix-Crataegi Fructus, Salviae Miltiorrhizae Radix et Rhizoma-Crataegi Fructus, and Polygoni Multiflori Radix-Crataegi Fructus. The 20 main ingredients were selected from the herb pairs and docked with 3 key hyperlipidemia targets, namely 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), peroxisome proliferator activated receptor-α (PPAR-α ) and niemann-pick C1 like 1 (NPC1L1) to further discuss the molecular mechanism of the high frequency herb pairs, by using the docking program, LibDock. To construct evaluation rules for the ingredients of herb pairs, the root-mean-square deviation (RMSD) value between computed and initial complexes was first calculated to validate the fitness of LibDock models. Then, the key residues were also confirmed by analyzing the interactions of those 3 proteins and corresponding marketed drugs. The docking results showed that hyperin, puerarin, salvianolic acid A and polydatin can interact with two targets, and the other five compounds may be potent for at least one of the three targets. In this study, the multi-target effect of high frequency herb pairs for lipid-lowering was discussed on the molecular level, which can help further researching new multi-target anti-hyperlipidemia drug.
Asteraceae ; chemistry ; Drugs, Chinese Herbal ; chemistry ; metabolism ; Humans ; Hydroxymethylglutaryl CoA Reductases ; chemistry ; genetics ; metabolism ; Hyperlipidemias ; drug therapy ; enzymology ; genetics ; metabolism ; Hypolipidemic Agents ; chemistry ; metabolism ; Membrane Proteins ; chemistry ; genetics ; metabolism ; Molecular Docking Simulation ; PPAR alpha ; chemistry ; genetics ; metabolism ; Protein Binding ; Pueraria ; chemistry

[ ABSTRACT] AIM:To investigate the changes of migration of lung adenocarcinoma cells promoted by IL-8 and the inner and outer mitochondrial membrane dynamic changes during this process.METHODS:Human lung adenocarci-noma cell line A549 was divided into control group and IL-8 group.Cell migration was analyzed by scratch detection and Transwell assay.The secretion of endogenous IL-8 was detected by ELISA.The protein levels of mitochondrial cytochrome C ( Cyt C) and mitochondrial outer membrane protein Tom20 was detected by Western blot.The mRNA expression of mito-chondrial fusion genes Mfn1, Mfn2 and OPA1 and fission genes Fis1, Drp1 and MTP18 was detected by RT-PCR.The morphological changes of mitochondria were observed by MitoTracker Red CMXRos dye staining and confocal microscopy. RESULTS:The migratory rate of A549 cells and endogenous secretion of IL-8 in A549 cells were higher than those in SPC-A-1 cells.The migratory rate of A549 cells was improved by IL-8 in a time-dependent manner.Compared with control group, the Tom20 protein expression was increased ( P<0.05 ) , and the Cyt C protein expression was decreased ( P<0.05).The expression of mitochondrial outer membrane fusion genes Mfn1 and Mfn2 was increased (P<0.05), and the expression of mitochondrial inner membrane fusion gene OPA1 was decreased (P<0.05).The expression of fission genes Drp1 and MTP18 were decreased (P<0.05), while the expression of Fis1 was no change (P>0.05).Under confocal microscope, the punctate aggregates in the mitochondria of the A549 cells treated with IL-8 were observed.CONCLU-SION:The migratory rate of A549 cells is increased by IL-8, which is related to the changes of mitochondrial fusion genes and the fission genes.

Objective To obtain the economic data in the aspects of cost-effectiveness and cost-utility of neonatal congenital hypothyroidism(CH) screening in Foshan City and to make assessment on the effect of screening works.Methods The economic related data were collected by the screening center,literatures,official resources and questionnaire investigation.The statistical tool and Tree Age Pro health decision analysis software were used to conduct the assessment on the cost-effectiveness and cost-utility of screening works.Results The screening program invested 17.95 million Yuan in total during 2000-2007,and the gain benefits was 117.69 million Yuan,net benefit was 9 975.52 ten thousand Yuan.The cost-benefit ratio was 1.00∶6.56.Each investing 3 216 Yuan could avoid a disability-adjusted life year.Conclusion The CH screening item has good economic applicability and is worth investing more funding for further promotion and popularization.

OBJECTIVETo study viruses infecting Pinellia ternata in China.

METHODSymptom observation, DAS-ELISA and RT-PCR detection were applied.

RESULT AND CONCLUSIONDuring a survey in early spring, SMV and CMV were both commonly distributed as main viruses infecting P. ternata collected from different areas in China. But DsMV was the virus which infected P. ternate in natural condition. The infection ratio of cultivated P. ternate by SMV and CMV were 71.4% and 14.3% respectively for 21 samples collected from Ningbo, Zhejiang province; 100% and 44.4% for 18 samples from Xiaoshan, Zhejiang province; 61.9% and 33.3% for 21 samples from Hebei province; 50.0% and 41.7% for 12 samples from Anhui province; 16.7% and 16.7% for 12 samples from Sichuan province; 31.3% and none for 16 samples from Beijing. And the infection ratio of 25 wild samples from different areas of China infected by SMV and CMV were both 20.0%.

China ; Cluster Analysis ; Cucumovirus ; genetics ; isolation & purification ; DNA, Complementary ; chemistry ; genetics ; Mosaic Viruses ; classification ; genetics ; isolation & purification ; Pinellia ; virology ; Plant Diseases ; virology ; Plants, Medicinal ; virology ; Sequence Analysis, DNA

The combined application of statins that inhibit HMG-CoA reductase and fibrates that activate PPAR-α can produce a better lipid-lowering effect than the simple application, but with stronger adverse reactions at the same time. In the treatment of hyperlipidemia, the combined administration of TCMs and HMG-CoA reductase inhibitor in treating hyperlipidemia shows stable efficacy and less adverse reactions, and provides a new option for the combined application of drugs. In this article, the pharmacophore technology was used to search chemical components of TCMs, trace their source herbs, and determine the potential common TCMs that could activate PPAR-α. Because there is no hyperlipidemia-related medication reference in modern TCM classics, to ensure the high safety and efficacy of all selected TCMs, we selected TCMs that are proved to be combined with statins in the World Traditional/Natural Medicine Patent Database, analyzed corresponding drugs in pharmacophore results based on that, and finally obtained common TCMs that can be applied in PPAR-α and combined with statins. Specifically, the pharmacophore model was based on eight receptor-ligand complexes of PPAR-α. The Receptor-Ligand Pharmacophore Generation module in the DS program was used to build the model, optimize with the Screen Library module, and get the best sub-pharmacophore, which consisted of two hydrogen bond acceptor, three hydrophobic groups and 19 excluded volumes, with the identification effectiveness index value N of 2. 82 and the comprehensive evaluation index CAI value of 1. 84. The model was used to screen the TCMD database, hit 5,235 kinds of chemical components and 1 193 natural animals and plants, and finally determine 62 TCMs. Through patent retrieval, we found 38 TCMs; After comparing with the virtual screening results, we finally got seven TCMs.
Acyl Coenzyme A ; metabolism ; Animals ; Databases, Factual ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Hydrophobic and Hydrophilic Interactions ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; chemistry ; pharmacology ; Lipid Metabolism ; drug effects ; Lipids ; blood ; Medicine, Chinese Traditional ; Models, Molecular ; Quantitative Structure-Activity Relationship ; Technology

This article discussed ZHU Lian's contributions to acupuncture-moxibustion scientific research from three aspects: building the scientific thought of "new acupuncture-moxibustion", constructing the first domestic acupuncture-moxibustion institution and opening the door to modern acupuncture-moxibustion scientific research. ZHU Lian's visionary thought of "new acupuncture-moxibustion" has influenced the following researchers till now. She established the acupuncture-Moxibustion therapeutic institute affiliated to the Ministry of Health, set up the acupuncture-Moxibustion research platforms and teams and made research cooperation. She firstly carried out acupuncture-Moxibustion clinical and basic scientific research, which started the acupuncture-Moxi- bustion scientific research in China. ZHU Lian is the Pioneer of Chinese acupuncture-Moxibustion scientific research.
Acupuncture ; education ; Acupuncture Therapy ; history ; China ; History, 20th Century ; Humans ; Moxibustion ; history