ISRN Pharmacology最新文献

We examined the effects of a chloroform extract of Hyptis albida (CHA) on inflammatory responses in mouse lipopolysaccharide (LPS) induced peritoneal macrophages. Our findings indicate that CHA inhibits LPS-induced production of tumor necrosis factor (TNF- α ) and interleukin-6 (IL-6). During the process, levels of cyclooxygenase-2 (COX-2), nitric oxide synthase (iNOS), and nitric oxide (NO) increased in the mouse peritoneal macrophages; however, the extract suppressed them significantly. These results provide novel insights into the anti-inflammatory actions of CHA and support its potential use in the treatment of inflammatory diseases.

We aimed to investigate the apoptotic effects of the methanolic extract of Dorema glabrum seed on WEHI-164, cancerous cells in comparison with L929, normal cells and compared them with the cytotoxic effects of Taxol. So, MTT test and DNA fragmentation assay were performed on cultured and treated cells. Also electrophoresis which was followed by immunoblotting was done to survey the production of Caspase-3 and Bcl2 proteins, and to inquire into their relative genes expression, RT-PCR was used. According to our findings, the methanolic extract of Dorema glabrum seed can alter cells morphology as they shrink and take a spherical shape and lose their attachment too. So, the plant extract inhibits cell growth albeit in a time- and dose-dependent manner and results in degradation of chromosomal DNA. Induction of apoptosis by the plant extract was proved by the reduction of pro-Caspase-3 and Bcl2 proteins and increase in Caspase-3 gene expression and decrease in that of bcl2 too. Our data well established the antiproliferative effect of methanolic extract of Dorema glabrum seed and clearly showed that the plant extract can induce apoptosis and not necrosis in vitro. These results demonstrated that Dorema glabrum seed might be a novel and attractive therapeutic candidate for tumor treatment.

The eating disorders (DCA) are complex systemic diseases with high social impact, which tend to become chronic with significant medical and psychiatric comorbidities. The literature data showed that there is good evidence to suggest the use of SSRIs, particularly at high doses of fluoxetine, in the treatment of BN reducing both the crisis of binge that the phenomena compensates and reducing the episodes of binge in patients with BED in the short term. Also, the topiramate (an AED) showed a good effectiveness in reducing the frequency and magnitude of episodes of binge with body weight reduction, both in the BN that is in the therapy of BED. To date, modest data support the use of low doses of second-generation antipsychotics in an attempt to reduce the creation of polarized weight and body shapes, the obsessive component, and anxiety in patients with AN. Data in the literature on long-term drug treatment of eating disorders are still very modest. It is essential to remember that the pharmacotherapy has, however, a remarkable efficacy in treating psychiatric disorders that occur in comorbidity with eating disorders, such as mood disorders, anxiety, insomnia, and obsessive-compulsive personality disorders and behavior.

The present study was aimed to investigate in vivo, in vitro antidiabetic activity of aqueous extract of Terminalia paniculata bark (AETPB) and characterize its possible phytoconstituents responsible for the actions. Type 2 diabetes was induced in rats by streptozotocin-nicotinamide (65 mg/kg-110 mg/kg; i.p.) administration. Oral treatment of AETPB using rat oral needle at 100 and 200 mg/kg doses significantly (P < 0.001) decreased blood glucose and glycosylated haemoglobin levels in diabetic rats than diabetic control rats. AETPB-treated diabetic rats body weight, total protein, insulin, and haemoglobin levels were increased significantly (P < 0.001) than diabetic control rats. A significant (P < 0.001) reduction of total cholesterol and triglycerides and increase in high-density lipoprotein levels were observed in type 2 diabetic rats after AETPB administration. Presence of biomarkers gallic acid, ellagic acid, catechin, and epicatechin in AETPB was confirmed in HPLC analysis. AETPB and gallic acid showed significant (P < 0.001) enhancement of glucose uptake action in presence of insulin in muscle cells than vehicle control. Also AETPB inhibited pancreatic α -amylase and α -glucosidase enzymes. In conclusion, the above actions might be responsible for the antidiabetic activity of AETPB due to presence of gallic acid and other biomarkers.

Olive oil is the major component of the Mediterranean diet and has rich history of nutritional and medicinal uses. In the present study, the antidepressant and anxiolytic effects and their neurochemical basis following repeated administration of extravirgin olive oil were monitored. Male albino Wistar rats were used during study. Animals of test group were given olive oil orally at the dose of 0.25 mL/kg daily for 4 weeks. Control rats received equal volume of water. Elevated-plus maze (EPM) test and forced swim test (FST) were performed for the assessment of anxiety and depression like symptoms. An increase in time spent in open arm in EPM and increased struggling time in FST following long-term administration of olive oil indicate that olive oil has anxiolytic and antidepressant properties. Neurochemical results showed that repeated administration of olive oil decreased the levels of brain 5-HT (5-hydroxytryptamine), 5-HIAA (5-hydroxyindoleacetic acid), and levels of DA (dopamine); however, levels of DA metabolite HVA (homovalinic acid) were increased. Hence, present findings suggest that olive oil has neuroprotective effects. It reduces behavioral deficits via altering 5-HT and DA metabolism. So it could be used as a therapeutic substance for the treatment of depression and anxiety.

In recent years, the activity of anaesthetic propofol on biological processes has been attracting attention. The effect of propofol on biochemical indices in animals is unknown. In this study, we examined the effects of propofol on lipid profile, antioxidant indices, and cardiovascular marker (CVM) enzymes in rats. The study consists of three groups of seven rats each. Group one received corn oil (Control) while groups two and three received propofol (doses of 2 and 4 mg/kg body weight, resp.). Results showed that administration of propofol caused a significant (P < 0.05) and dose-dependent increase in the levels of total bilirubin. Propofol at 2 and 4 mg/kg increased the levels of serum total cholesterol by 74% and 55%, triglycerides by 97% and 115%, and LDL-C (low-density lipoprotein-cholesterol) by 45% and 73%, respectively, while HDL-C (high-density lipoprotein-cholesterol) decreased by 41% and 54%, respectively. Propofol significantly (P < 0.05) increased the levels of the hepatic reduced glutathione (GSH) and activities of GSH-dependent enzymes. Propofol at 2 and 4 mg/kg increased the activities of CVM enzymes: lactate dehydrogenase by 1.7 and 1.8 folds and creatinine phosphokinase by 2.0 and 2.1 folds, respectively. Taken together, propofol increased the levels of GSH and GSH-dependent enzymes but adversely affected the lipid profile of the rats.

Stathmin, a microtubule-destabilizing phosphoprotein, is highly expressed in ovarian cancer, but the pathophysiological significance of this protein in ovarian carcinoma cells remains poorly understood. This study reports the involvement of stathmin in the mTOR/HIF-1 α /VEGF pathway in ovarian clear cell adenocarcinoma (CCA) during hypoxia. HIF-1 α protein and VEGF mRNA levels were markedly elevated in RMG-1 cells, a CCA cell line, cultured under hypoxic conditions. Rapamycin, an inhibitor of mTOR complex 1, reduced the level of HIF-1 α and blocked phosphorylation of ribosomal protein S6 kinase 1 (S6K), a transcriptional regulator of mTOR, demonstrating that hypoxia activates mTOR/S6K/HIF-1 α signaling in CCA. Furthermore, stathmin knockdown inhibited hypoxia-induced HIF-1 α and VEGF expression and S6K phosphorylation. The silencing of stathmin expression also reduced Akt phosphorylation, a critical event in the mTOR/HIF-1 α /VEGF signaling pathway. By contrast, stathmin overexpression upregulated hypoxia-induced HIF-1 α and VEGF expression in OVCAR-3 cells, another CCA cell line. In addition, suppression of Akt activation by wortmannin, a phosphoinositide 3-kinase (PI3K) inhibitor, decreased HIF-1 α and VEGF expression. These results illustrate that regulation of HIF-1 α through the PI3K/Akt/mTOR pathway is controlled by stathmin in CCA. Our findings point to a new mechanism of stathmin regulation during ovarian cancer.

Objective. To develop a simple and rapid high-performance liquid chromatography (HPLC) method for measuring moxifloxacin concentration in human plasma. Methods. Following a single step liquid-liquid extraction, analytes along with an internal standard (IS) were separated using an isocratic mobile phase of 0.1% triethylamine (adjusted pH to 4.8 with phosphoric acid)/acetonitrile (80/20, v/v) at flow rate of 1 mL/min on reverse phase Kromasil C18 column (250 mm × 4.6 mm, 5  μ m) at room temperature. Results. Total analytical run time for selecting moxifloxacin was 15 min. The assays exhibited good linearity (r (2) = 0.9998) over the studied range of 25 to 5000 ng/mL. The absolute recovery rate of low, medium, and high concentrations were 69.88%, 78.86%, and 78.51%, respectively. The relative recovery rates were 98.50%, 96.61%, and 101.79%, respectively. Coefficient of variation and error at both of the intraday and interday assessments were less than 4.7%. Conclusions. The results indicated that this method is a simple, rapid, precise and accurate assay for the determination of moxifloxacin concentrations in human plasma. This validated method is sensitive and reproducible enough to be used in pharmacokinetic studies.

The present study was done to evaluate the antiurolithiatic activity of ethanolic extract of roots (ELC 200 mg/kg) and oleanolic acid (OA 60 mg/kg, O.A. 80 mg/kg, O.A. 100 mg/kg) isolated from roots of Lantana camara in albino wistar male rats using zinc disc implantation induced urolithiatic model. The group in which only zinc disc was implanted without any treatment showed increase in calcium output (23  ± 2.7 mg/dL). Cystone receiving animals showed significant protection from such change (P < 0.01). Treatment with OA and ELC significantly reduced the calcium output at a dose of OA 60 mg/kg (P < 0.01), OA 80 mg/kg (P < 0.01), ELC 200 mg/kg (P < 0.01), and OA 100 mg/kg (P < 0.001), as compared with zinc disc implanted group. The average weight of zinc discs along with the deposited crystals in the only disc implanted group was found to be 111 ± 8.6 mg. Group that received Cystone 500 mg/kg showed significant reduction in the depositions (P < 0.001). Similarly, the rats which received OA and ELC showed reduced formation of depositions around the zinc disc (P < 0.001). The X-ray images of rats also showed significant effect of OA and ELC on urolitiasis. Thus, OA and ELC showed promising antiurolithiatic activity in dose dependant manner.

The immunosuppressant drug cyclosporin A (CyA) has been used in diseases with immunological basis and in transplant patients. Nephrotoxicity and hepatotoxicity are the main adverse effects of this drug. To find a protective drug against those effects we assayed the cardioprotector Trimetazidine (TMZ) and vitamin E, used as nutritional supplements to alleviate oxidative stress. Six groups of eight male Wistar rats each were prepared (groups A-F): A, control; B, vitamin E (10 mg/Kg/day); C, TMZ (20 mg/Kg/day); D, 25 mg/Kg/day CyA; E, CyA and vitamin E (25 mg/Kg/day CyA + 10 mg/Kg/day Vit E); F, TMZ for 20 days (20 mg/kg/day); and then CyA (25 mg/kg/day) and TMZ (20 mg/Kg/day). The experiment lasted 120 days. The exposure of rats to CyA promoted nephrotoxicity and hepatotoxicity with an increase in serum urea, creatinine, and glutamate dehydrogenase (GLDH). Structural and ultrastructural studies of liver and kidney were performed. Group D showed adverse effects induced by CyA since statistically significant differences were found with respect to the control group (A). Vitamin E (E) showed no protective effect. Pretreatment with TMZ (F) attenuated the adverse effects of CyA. We conclude that CyA-induced nephrotoxicity and hepatotoxicity are attenuated by the cytoprotective effect of TMZ. TMZ inhibits the reabsorption and, consequently, the accumulation of CyA in the cell. The antioxidant capacity of vitamin E did not improve the effect of CyA.