PubMed Journal Database | Acta pharmacologica Sinica - Page: 4

The essential role for aromatic cluster in the β3 adrenergic receptor.

Aim:To explore the function of the conserved aromatic cluster F213(5.47), F308(6.51), and F309(6.52) in human β3 adrenergic receptor (hβ3AR).Methods:Point mutation technology was used to produce plasmid mutations of hβ3AR. HEK-293 cells were transiently co-transfected with the hβ3AR (wild-type or mutant) plasmids and luciferase reporter vector pCRE-luc. The expression levels of hβ3AR in the cells were determined by Western blot analysis. The constitutive signalling and the signalling induced by the β3...

Tissue cholesterol content alterations in streptozotocin-induced diabetic rats.

Aim:Diabetes is associated with elevated serum total cholesterol level and disrupted lipoprotein subfractions. The aim of this study was to examine alterations in the tissue cholesterol contents closely related to diabetic complications.Methods:Intraperitoneal injection of streptozotocin was used to induce type 1 diabetes in adult male Sprague-Dawley rats. On d 35 after the injection, liver, heart, intestine, kidney, pancreas, cerebral cortex and hippocampus were isolated from the rats. The content of total...

Excess genistein suppresses the synthesis of extracellular matrix in female rat mandibular condylar cartilage.

Aim:To investigate the effect of excess genistein on the extracellular matrix in mandibular condylar cartilage of female rats in vivo.Methods:Female SD rats were administered through oral gavage with genistein (50 mg/kg) or placebo daily for 6 weeks. The morphological changes of temporomandibular joints were studied with HE staining. The expression of cartilage matrix compounds (aggrecan and collagen type II), estrogen-related molecules (aromatase, estradiol, ERα and ERβ) and proliferating cell nuclear an...

Arctigenin alleviates ER stress via activating AMPK.

Aim:To investigate the protective effects of arctigenin (ATG), a phenylpropanoid dibenzylbutyrolactone lignan from Arctium lappa L (Compositae), against ER stress in vitro and the underlying mechanisms.Methods:A cell-based screening assay for ER stress regulators was established. Cell viability was measured using MTT assay. PCR and Western blotting were used to analyze gene and protein expression. Silencing of the CaMKKβ, LKB1, and AMPKα1 genes was achieved by RNA interference (RNAi). An ATP bioluminescen...

Atorvastatin enhances neurite outgrowth in cortical neurons in vitro via up-regulating the Akt/mTOR and Akt/GSK-3β signaling pathways.

Aim:To investigate whether atorvastatin can promote formation of neurites in cultured cortical neurons and the signaling mechanisms responsible for this effect.Methods:Cultured rat cerebral cortical neurons were incubated with atorvastatin (0.05-10 μmol/L) for various lengths of time. For pharmacological experiments, inhibitors were added 30 min prior to addition of atorvastatin. Control cultures received a similar amount of DMSO. Following the treatment period, phase-contrast digital images were taken. Di...

Vam3, a derivative of resveratrol, attenuates cigarette smoke-induced autophagy.

Aim:To appraise the efficacy of Vam3 (Amurensis H), a dimeric derivative of resveratrol, at inhibiting cigarette smoke-induced autophagy.Methods:Human bronchial epithelial cells were treated with cigarette smoke condensates, and a chronic obstructive pulmonary disease (COPD) model was established by exposing male BALB/c mice to cigarette smoke. The protein levels of the autophagic marker microtubule-associated protein 1A/1B-light chain 3 (LC3), Sirtuin 1 (Sirt1), and foxhead box O 3a (FoxO3a) were examined...

Pretreatment with IFN-α increases resistance to imatinib mesylate in patients with chronic myelocytic leukemia.

Pharmacophore-based virtual screening and density functional theory approach to identifying novel butyrylcholinesterase inhibitors.

Aim:To identify the critical chemical features, with reliable geometric constraints, that contributes to the inhibition of butyrylcholinesterase (BChE) function.Methods:Ligand-based pharmacophore modeling was used to identify the critical chemical features of BChE inhibitors. The generated pharmacophore model was validated using various techniques, such as Fischer's randomization method, test set, and decoy set. The best pharmacophore model was used as a query in virtual screening to identify novel scaffold...

The biphasic redox sensing of SENP3 accounts for the HIF-1 transcriptional activity shift by oxidative stress.

Aim:To investigate the mechanisms underlying the biphasic redox regulation of hypoxia-inducible factor-1 (HIF-1) transcriptional activity under different levels of oxidative stress caused by reactive oxidative species (ROS).Methods:HeLa cells were exposed to different concentrations of H(2)O(2) as a simple model for mild and severe oxidative stress. Luciferase reporter assay and/or quantitative real-time PCR were used to investigate the transcriptional activity. Immunoblot was used to detect protein express...

Anisomycin induces glioma cell death via down-regulation of PP2A catalytic subunit in vitro.

Aim:To examine the effects of anisomycin on glioma cells and the related mechanisms in vitro.Methods:The U251 and U87 human glioblastoma cell lines were tested. The growth of the cells was analyzed using a CCK-8 cell viability assay. Apoptosis was detected using a flow cytometry assay. The expression of proteins and phosphorylated kinases was detected using Western blotting.Results:Treatment of U251 and U87 cells with anisomycin (0.01-8 μmol/L) inhibited the cell growth in time- and concentration-dependent...

A novel small molecule, HK-156, inhibits lipopolysaccharide-induced activation of NF-κB signaling and improves survival in mouse models of sepsis.

Aim:To characterize a small molecule compound HK-156 as a novel inhibitor of the nuclear factor κB (NF-κB) signaling pathway.Methods:THP-1 monocytes and HEK293/hTLR4A-MD2-CD14 cells were tested. HK-156 and compound 809, an HK-156 analogue, were synthesized. A luciferase assay was used to evaluate the transcriptional activity of NF-κB. The levels of cytokines were measured with cytokine arrays, ELISA and quantitative PCR. An electrophoretic mobility shift assay (EMSA), immunofluorescence, Western blot and...

The mineralocorticoid receptor-p38MAPK-NFκB or ERK-Sp1 signal pathways mediate aldosterone-stimulated inflammatory and profibrotic responses in rat vascular smooth muscle cells.

Aim:To explore the signalling pathways involved in aldosterone-induced inflammation and fibrosis in rat vascular smooth muscle cells (VSMCs).Methods:Using Western blotting and real-time RT-PCR, we investigated the effects of aldosterone on the expression of cyclooxygenase-2 (Cox-2) and IL-6, two important proinflammatory factors, and TGFβ1, a critical profibrotic factor, in VSMCs.Results:Aldosterone treatment significantly increased the expression of Cox-2 and IL-6 and activation of p38MAPK and NF-κB. The...

Population pharmacokinetics and pharmacodynamics of bivalirudin in young healthy Chinese volunteers.

Aim:To investigate the population pharmacokinetics (PK) and pharmacodynamics (PD) of bivalirudin, a synthetic bivalent direct thrombin inhibitor, in young healthy Chinese subjects.Methods:Thirty-six young healthy volunteers were randomly assigned into 4 groups received bivalirudin 0.5 mg/kg, 0.75 mg/kg, and 1.05 mg/kg intravenous bolus, 0.75 mg/kg intravenous bolus followed by 1.75 mg/kg intravenous infusion per hour for 4 h. Blood samples were collected to measure bivalirudin plasma concentration and activ...

siRNA against plasminogen activator inhibitor-1 ameliorates bleomycin-induced lung fibrosis in rats.

Aim:Plasminogen activator inhibitor-1 (PAI-1) is involved in the progression of pulmonary fibrosis. The present study was undertaken to examine the effects on pulmonary fibrosis of silencing PAI-1 expression with small interfering RNA (siRNA) and to assess the possible underlying mechanisms.Methods:Male Wistar rats were subjected to intratracheal injection of bleomycin (BLM, 5 mg/kg, 0.2 mL) to induce pulmonary fibrosis. Histopathological changes of lung tissue were examined with HE or Masson's trichrome st...

Pharmacokinetic/pharmacodynamic studies on exenatide in diabetic rats.

Aim:To quantitatively evaluate the blood glucose-lowering effect of exenatide in diabetic rats.Methods:Male Harlan-Sprague-Dawley rats were treated with high-fat diet/streptozotocin to induce type 2 diabetes. After subcutaneous administration of a single dose of exenatide (4.2, 42, or 210 μg/kg), serum exenatide, insulin concentration and blood glucose were measured. The pharmacokinetics of exenatide was characterized by a two-compartment model with first-order absorption. Insulin turnover was characterize...

Phosphorylation of endothelial NOS contributes to simvastatin protection against myocardial no-reflow and infarction in reperfused swine hearts: partially via the PKA signaling pathway.

Aim:The cholesterol-lowering drugs statins could enhance the activities of endothelial nitric oxide synthase (eNOS) and protect myocardium during ischemia and reperfusion. The aim of this study was to examine whether protein kinase A (PKA) was involved in statin-mediated eNOS phosphorylation and cardioprotection.Methods:6-Month-old Chinese minipigs (20-30 kg) underwent a 1.5-h occlusion and 3-h reperfusion of the left anterior descending coronary artery (LAD). In the sham group, the LAD was encircled by a s...

Enhancement of cellular uptake and cytotoxicity of curcumin-loaded PLGA nanoparticles by conjugation with anti-P-glycoprotein in drug resistance cancer cells.

Aim:To compare the anti-cancer activity and cellular uptake of curcumin (Cur) delivered by targeted and non-targeted drug delivery systems in multidrug-resistant cervical cancer cells.Methods:Cur was entrapped into poly (DL-lactide-co-glycolide) (PLGA) nanoparticles (Cur-NPs) in the presence of modified-pluronic F127 stabilizer using nano-precipitation technique. On the surface of Cur-NPs, the carboxy-terminal of modified pluronic F127 was conjugated to the amino-terminal of anti-P-glycoprotein (P-gp) (Cur-...

Combined administration of anisodamine and neostigmine produces anti-shock effects: involvement of α7 nicotinic acetylcholine receptors.

Aim:To evaluate the anti-effects of anisodamine and neostigmine in animal models of endotoxic and hemorrhagic shock.Methods:Kunming mice were injected with lipopolysaccharide (LPS 30 mg/kg, ip) to induce endotoxic shock. Anisodamine (12.5, 25, and 50 mg/kg, ip) and neostigmine (12.5, 25, and 50 μg/kg, ip) were administered immediately after LPS injection. Survival rate was monitored, and the serum levels of TNF-α and IL-1β were analyzed using ELISA assays. The effects of anisodamine and neostigmine were...

Pirarubicin inhibits multidrug-resistant osteosarcoma cell proliferation through induction of G(2)/M phase cell cycle arrest.

Aim:Pirarubicin (THP) is recently found to be effective in treating patients with advanced, relapsed or recurrent high-grade osteosarcoma. In this study, the effects of THP on the multidrug-resistant (MDR) osteosarcoma cells were assessed, and the underlying mechanisms for the disruption of cell cycle kinetics by THP were explored.Methods:Human osteosarcoma cell line MG63 and human MDR osteosarcoma cell line MG63/DOX were tested. The cytotoxicity of drugs was examined using a cell proliferation assay with t...

Biphasic regulation of P-glycoprotein function and expression by NO donors in Caco-2 cells.

Aim:To investigate the effects of nitric oxide (NO) donors on the function and expression of P-glycoprotein (P-gp) in Caco-2 cells.Methods:Caco-2 cells were exposed to NO donors for designated times. P-gp function and expression were assessed using Rhodamine123 uptake assay and Western blotting, respectively. Intracellular reactive oxygen species (iROS) and intracellular reactive nitrogen species (iRNS) levels were measured using ROS and RNS assay kits, respectively.Results:Exposure of Caco-2 cells to 0.1 o...

β-asarone protects PC12 cells against OGD/R-induced injury via attenuating Beclin-1-dependent autophagy.

Aim:To explore the effects of β-asarone from Acorus Tatarinowii Schott on autophagy in an ischemic stroke model of PC12 cells.Methods:The ischemic stroke model of PC12 cells was made by OGD/R (2 h oxygen-glucose deprivation followed by 24 h reperfusion). Drug administration was started 1 h before OGD and last for 3 h. Then the cells were incubated in the drug-free and full culture medium under normoxic conditions for 24 h. After the treatments, Beclin-1, intracellular free calcium concentration ([Ca(2+)](i...

Preclinical assessment of the distribution, metabolism, and excretion of S-propargyl-cysteine, a novel H(2)S donor, in Sprague-Dawley rats.

Aim:To study the distribution, metabolism and excretion of S-propargyl-cysteine (SPRC), a novel hydrogen sulfide (H2S) donor, after oral administration in rats.Methods:Adult Sprague-Dawley rats were used. The tissue distribution of [(35)S] SPRC-derived radioactivity was measured using a liquid scintillation counter. The plasma protein binding of SPRC was examined using 96-well equilibrium dialysis. The excretion of SPRC in urine, bile and feces was analyzed using the LC-MS/MS method. The major metabolites i...

Protective effects of tiopronin against high fat diet-induced non-alcoholic steatohepatitis in rats.

Aim:To study the protective effects of tiopronin against high fat diet-induced non-alcoholic steatohepatitis in rats.Methods:Male Sprague-Dawley rats were given a high-fat diet for 10 weeks. The rats were administered tiopronin (20 mg/kg) or a positive control drug ursodeoxycholic acid (UDCA, 15 mg/kg) via gavage daily from week 5 to week 10. After the rats were sacrificed, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), free fatty...

E-cadherin promotes proliferation of human ovarian cancer cells in vitro via activating MEK/ERK pathway.

Aim:E-cadherin is unusually highly expressed in most ovarian cancers. This study was designed to investigate the roles of E-cadherin in the carcinogenesis and progression of ovarian cancers.Methods:Human ovarian adenocarcinoma cell line SKOV-3 was examined. E-cadherin gene CDH1 in SKOV-3 cells was knocked down via RNA interference (RNAi), and the resultant variation of biological behavior was observed using CCK-8 and colony formation experiment. E-cadherin-mediated Ca(2+)-dependent cell-cell adhesion was us...

The regulation of N-terminal Huntingtin (Htt552) accumulation by Beclin1.

Aim:Huntingtin protein (Htt) was a neuropathological hallmark in human Huntington's Disease. The study aimed to investigate whether the macroautophagy regulator, Beclin1, was involved in the degradation of Htt.Methods:Primary cultured neurons and PC12 cells were used. pDC316 adenovirus shuttle plasmid mediated the expression of wild type Htt-18Q-552 and mutant Htt-100Q-552 in PC12 cells. Autophagy was evaluated by the protein expression levels of autophagy associated proteins, LC3 II and Beclin1 as well as...