Animals ; Calcineurin ; metabolism ; Diet, High-Fat ; Dietary Fats ; administration & dosage ; Male ; Myocardium ; metabolism ; Physical Conditioning, Animal ; physiology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Superoxides ; antagonists & inhibitors

This study aims to investigate the effect of total flavones of Fructus Chorspondiatis (TFFC) on the mRNA and protein expression of collagen type I and III of rat cardiac fibroblasts (CFs) induced by angiotensin II (Ang II), and explore its anti-myocardial fibrosis molecular mechanism. Neonatal rat CFs were prepared from Sprague-Dawley rats (1-3 d after birth). The expression of collagen type I and III mRNA and protein were measured by RT-PCR and Western blotting, respectively. The study showed that stimulation of neonatal rat CFs with 100 nmol.L-1 of Ang II for 72 h resulted in a significant increase of the expression of collagen type I and III mRNA and protein. The changes on the expression level were blocked by TFFC. The results demonstrated that TFFC can inhibit myocardial fibrosis induced by Ang II in rats, which is probably associated with the collagen type I and III mRNA and protein levels up-regulated by Ang II, and TFFC was shown to decrease the expression levels of collagen type I and III mRNA and protein.
Anacardiaceae ; chemistry ; Angiotensin II ; pharmacology ; Animals ; Animals, Newborn ; Cells, Cultured ; Collagen Type I ; genetics ; metabolism ; Collagen Type III ; genetics ; metabolism ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacology ; Fibroblasts ; cytology ; metabolism ; Flavones ; administration & dosage ; isolation & purification ; pharmacology ; Fruit ; chemistry ; Myocardium ; cytology ; metabolism ; Plants, Medicinal ; chemistry ; RNA, Messenger ; metabolism ; Rats ; Rats, Sprague-Dawley

Adult ; Female ; Humans ; Magnetic Resonance Imaging ; Neuroma, Acoustic ; pathology ; surgery

In this study, the effect of heparin-derived oligosaccharide (HDO) on platelet-derived growth factor (PDGF) induced vascular smooth muscle cells (VSMCs) proliferation and the related signal transduction mechanisms were investigated. MTT assays were used to measure VSMCs proliferation. Cell cycle distribution was analyzed by flow cytometry. The level of key regulatory proteins in PKC, MAPK and Akt/PI3K pathways were determined by RT-PCR, Western blot and immunocytochemical methods. Meanwhile, mRNA expressions of some proto-oncogenes were assayed by RT-PCR method. Our data showed that HDO (0.01, 0.1 and 1 μmol · L(-1)) inhibited 30 ng · mL(-1) PDGF-induced VSMCs proliferation in a dose-dependent manner, blocked the G1/S transition and inhibited the level of key regulatory proteins and some proto-oncogenes (P < 0.05). The results showed that HDO may decrease the key regulatory proteins expression, hence suppress the transcription of proto-oncogene and G1/S transition, finally inhibiting VSMCs proliferation.
Cell Cycle ; Cell Proliferation ; drug effects ; Cells, Cultured ; Flow Cytometry ; Heparin ; pharmacology ; Humans ; Muscle, Smooth, Vascular ; cytology ; Myocytes, Smooth Muscle ; cytology ; drug effects ; Oligosaccharides ; pharmacology ; Platelet-Derived Growth Factor ; pharmacology ; Signal Transduction

Steroidal saponins have a wide range of pharmacological effects and biological activities, such as anti-tumor, antifungal, hypoglycemic, immune regulation, insecticides, etc. In the last ten years, some new structures of steroidal saponins compounds were found from natural plants, they have some new and different activities. In order to accelerate the research on the drug innovation of steroidal saponins, we summarized the new progress of the research on such compounds.
Animals ; Anti-Inflammatory Agents ; pharmacology ; Antifungal Agents ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Humans ; Hypoglycemic Agents ; pharmacology ; Saponins ; pharmacology ; Steroids ; pharmacology

It is the objective of this paper to study pharmacokinetics-pharmacodynamics (PK-PD) characteristics of ginsenoside Rg1 and Rb1 on the effect of inducing nitric oxide (NO) release after intravenous administration of Shengmai injection to rats with myocardial ischemia. The model of myocardial ischemia rats was produced by subcutaneous injection of isoproterenol. The serum samples were collected at different time points after intravenous administration of Shengmai injection to rats with the dose of 10.8 mL x kg(-1). The concentrations of ginsenoside Rg1 and Rb1 in serum were determined, and then the concentration-time curves were drawn. Pharmacokinetic parameters of ginsenoside Rg1 and Rb1 were calculated after the construction of pharmacokinetic models. Meanwhile, NO2- and NO3-, the metabolites of NO, in serum were determined, and then the effect-time curve was drawn. The combined PK-PD model was established based on the theory of effect compartment by Sheiner et al. Then pharmacodynamic parameters were calculated. The results indicated that the pharmacokinetics of ginsenoside Rg1 and Rb1 conformed to a two-compartment model. Ginsenoside Rg1 and Rb1 exhibited quick and slow elimination in rats respectively. The effect of Shengmai injection on inducing NO release did not relate directly with and lagged behind the concentrations of ginsenoside Rg1 and Rb1 in serum. The effect exhibited good correlation with ginsenoside Rg1 and Rb1 levels in effect compartment. The relationship between effect and serum concentration fits Sigmoid-E(max) model. This study successfully established the combined PK-PD model of ginsenoside Rg1 and Rb1 after intravenous administration of Shengmai injection to rats. The model can efficiently predict the concentration and effect of Shengmai injection in vivo.
Administration, Intravenous ; Animals ; Ginsenosides ; administration & dosage ; pharmacokinetics ; Humans ; Male ; Myocardial Ischemia ; drug therapy ; metabolism ; Nitric Oxide ; metabolism ; Rats ; Rats, Sprague-Dawley

Objective To investigate the relationship between amnestic mild cognitive impairment and functional genes associated with hyperphosphorylated tau protein.Methods One hundred and sixteen amnestic mild cognitive impairment (aMCI) patients and 93 normal controls were recruited for the study.Multi-dimension neuropsychologic tests were used to assess the cognitive function extensively.MassARRAY and iPlex systems were used to measure candidate SNP polymorphisms,analyze genotypic,allelic or haplotypic distributions and their interaction with ApoE ε4 and the correlation with the cognitive function in the subjects.Results ( 1 ) The scores of neuropsychologic tests in memory domain ( Auditory Verbal Learning Test (AVLT)-first immediate recall,AVLT-second immediate recall,AVLT-second immediate recall,AVLT-5 minute delayed recall,AVLT-20 minute delayed recall,AVLT-recognition,Rey-Osterrich Comolex Test-delay) in aMCI patients ( 3.0 ( 0-7.0 ),5.0 ( 1.0-10.0),6.0 ( 1.0-11.0 ),4.0 (0-11.0),3.0(0-10.0),20.0(8.0-24.0),11.2 ±8.3) were significantly lower than those in the normal controls(4.0(0-9.0),7.0(2.0-11.0),9.0(3.0-12.0),8.0(0-12.0),8.0(0-12.0),22.0 (10.0-24.0),16.1±8.0) (Z=-3.592,-6.802,-6.408,-8.173,-8.533,-5.647 andt=4.216 respectively,all P ＜0.01 ) ; (2) Genotypic distributions of rs242562 GG in aMCI (7.826％ ) were significantly lower than those in normal controls (20.65％,OR =0.3525,95％ CI 0.1411-0.8807,P =0.024 98),however there were no differences in the genotypic,allelic or haplotypic distributions between aMCI patients and controls of glycogen synthase kinase-3β,cyclin dependent protein kinase-5,calcium and calmodulin-dependent protein kinase-Ⅱ,cell division cycle 2,dual-specificity tyrosine-phosphorylation regulated kinase 1A and low density lipoprotein receptor-related protein 6; (3) MAPT/STH rs242562 genotype was correlated with AVLT-immediate recall,AVLT-delayed recall,Rey-Osterrieth Complex Test,Rey-Osterrieth Complex Test-delayed recall and Clock Drawing Test (H =9.763,12.258,10.508,9.624,10.767,F =3.700,3.123 and H =6.591 respectively,all P ＜ 0.05 ) ; (4) There were no differences in the distributions of MAPT/STH rs242562 GG genotype and ApoE ε4 haplotype between aMCI patients and normal controls.Conclusions MAPT/STH rs242562 GG genotype decreases the genetic risk of aMCI,which might have important role in memory function in aMCI.The interaction between rs242562 GG and ApoE ε4 doesn' t affect the susceptibility to aMCI.

Objective To detect the expression of bone morphogenetic protein receptor Ⅱ ( BMPR Ⅱ ) in human focal cortical dysplasia ( FCD Ⅱ b). Methods Fourteen specimens of FCD Ⅱ b surgically removed and pathologically verified were collected from June 2008 to June 2010 and the expression of BMPR Ⅱ in the normal brain tissues and the pathological specimens was detected by means of immunohistochemistry and western blot. Results In the normal brain tissues, BMPR Ⅱ was widely expressed in the cortical neurons of the grey matter, with no positive immunostaining in the white matter. In the cortical lesion of FCD Ⅱ b, BMPR Ⅱ was strongly expressed in the misshapen cells including balloon cells (BCs) , dysmorphic neurons (DNs) and giant neurons (GNs). Positive BMPR Ⅱ expression was also observed in the reactive astroeytes and low level expression of BMPR Ⅱ was found in the normal-appearing (NA) neurons. Western-blot analysis showed that BMPR Ⅱ expression tended to be lowered in the FCD Ⅱ b specimens compared with the normal brain tissues ( P < 0. 05 ). Conclusion The expression of BMPR Ⅱ is altered and reduced in the FCD Ⅱ b, suggesting that BMP signal pathway may participate in the pathogenesis of FCD.