Acetamides ; pharmacology ; Animals ; Bridged-Ring Compounds ; poisoning ; Disease Models, Animal ; Female ; Male ; Rats ; Rats, Sprague-Dawley ; Troponin I ; blood

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

Objective To study the effect of oxymatrine on p-STAT3 and PIAS3 signaling molecule and it's mRNA expression in the proliferation of the human mesangial cells (HMCs) induced by lipopolysaccharide(LPS) and to explore their relationship. Methods HMCs were divided into three groups: control group, LPS group and oxymatrine group. HMC proliferation was detected by methyl thiazolyl tetrazolium (MTT) assay. Type Ⅳ collagen in the supernatants of the cultured HMCs was detected by ELISA at 12, 24, 48 hours respectively. At the same time, the protein and mRNA expressions of p-STAT3 and PIAS3 were measured by Western blot and real-time quantitative RT-PCR. Results The cell proliferation, the mRNA and protein expression of type Ⅳ collagen, p-STAT3 in LPS group were increased compared with the control group (P<0.01), but they were decreased in oxymatrine group (P < 0.01). The expressions of protein and mRNA of PIAS3 in LPS group were decreased significantly compared with control group (P<0.01), but they were increased in oxymatrine group (P<0.01). Conclusion Oxymatrine can down-regulate the expression of p-STAT3 and up-regulate the expression of PIAS3, which plays an important role in the process of LPS-induced HMCs proliferation.

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

Chlorine ; Computer Simulation ; Computers, Analog ; Diffusion ; Software

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

Amoxicillin ; adverse effects ; Anti-Bacterial Agents ; adverse effects ; Child ; Humans ; Male ; Renal Insufficiency ; chemically induced

Objectives To determine the effects of Matrine (Ma) on signal transducers and activators of transcription (STAT) 1, 3, connective tissue growth factor (CTGF) and platelet -derived growth factor (PDGF) in glomerular mesangial cells (MC) induced by lipopolysaccharide (LPS), and to explore the protective mechanisms of Ma. Methods Ma were added to cultured glomerular mesangial cells which were exposed to LPS for 12, 24 and 48 hours. Real time polymerase chain reaction were used to determine STAT1, 3, CTGF, PDGF mRNA, The protein expression of STATI, 3 and p-STAT1, 3 were observed by Western blot. Results Compared with the control group, MC proliferation of the LPS group (10μg/ml) significantly increased, which were suppressed in the Ma (320 μg/ml) group (P < 0.01) at 12, 24, 48 hours. The expression of STAT1, 3, CTGF, PDGF mRNA and the levels of p-STAT1 , p-STAT3 protein was significantly increased in MC under LPS medium at 12, 24, 48 hours, which were obviously lower in Ma group than those of the LPS group, especially at 24, 48 hours. Conclusions The protective mechanisms of Matrine is considered to down-regulate the expression of STAT1, 3, CTGF and PDGF.

Noise, Occupational ; prevention & control ; Occupational Health Services ; standards ; Threshold Limit Values

Objective To observe the effect of oxymatrine(OM) on the expressions of p-STAT1 and PIAS1 signaling molecules at protein and mRNA levels in the proliferation of the human mesangial cells(HMC) induced by lipopolysaccharide(LPS) and explore the relationship between them.Methods HMCs were primarily cultured from a 4-month-old aborted human fetus(with informed consent and approved by the Ethics Committee of Lanzhou University),and then divided into 3 groups,that is,control group,LPS group(10 ng/ml) and OM group(LPS 10 ng/ml and OM 320 mg/L).After cultured for 12,24 and 48 h respectively,HMC proliferation were analyzed by methyl thiazolyl tetrazolium(MTT) assay and type Ⅳ collagen in the supernatants were detected by ELISA.At the same time points,the cells lysates were collected for the mRNA and protein expressions of p-STAT1 and PIAS1 by real-time quantitative RT-PCR and Western blot analysis.Results The cell proliferation of LPS group was faster and the type Ⅳ collagen protein was increased more than the control group(P