ISRN Pharmacology最新文献

Background. Global myocardial ischemia reperfusion injury after heart transplantation is believed to impair graft function and aggravate both acute and chronic rejection episodes. Objectives. To assess the possible protective potential of MK-886 and 3,5-diiodothyropropionic acid DITPA against global myocardial ischemia reperfusion injury after heart transplantation. Materials and Methods. Adult albino rats were randomized into 6 groups as follows: group I sham group; group II, control group; groups III and IV, control vehicles (1,2); group V, MK-886 treated group. Donor rats received MK-886 30 min before transplantation, and the same dose was repeated for recipients upon reperfusion; in group VI, DITPA treated group, donors and recipients rats were pretreated with DITPA for 7 days before transplantation. Results. Both MK-886 and DITPA significantly counteract the increase in the levels of cardiac TNF- α , IL-1 β , and ICAM-1 and plasma level of cTnI (P < 0.05). Morphologic analysis showed that both MK-886 and DITPA markedly improved (P < 0.05) the severity of cardiac injury in the heterotopically transplanted rats. Conclusions. The results of our study reveal that both MK-886 and DITPA may ameliorate global myocardial ischemia reperfusion injury after heart transplantation via interfering with inflammatory pathway.

The present study was carried out to evaluate antiarthritic potential and phytochemical screening of various extracts of Ficus lacor aerial roots. The antiarthritic activity was evaluated by adjuvant-induced arthritis at the dose of 50 and 100 mg/kg body weight and the standard drug used was indomethacin. The extracts administered in higher doses reduced the lesions to a greater extent showing a dose-dependent decrease in lesions comparable with standard drug indomethacin. The extracts of FLPE and FLET showed significant increase in body weight as compared to arthritic control group as well as an increase in liver weight, a decrease in liver weight, and an increase in spleen weight in arthritis control. The extracts of FLPE and FLET showed significant decrease in WBC count, increase in hemoglobin contents, and RBC count as compared to control group. FLEA and FLCF were not able to produce a significant effect. There was significant reduction in production of IL-1 and TNF- α level between model group and control group in serum. In conclusion, we demonstrate that, at 100 mg/kg body weight, doses of FLPE and PLET extracts were highly effective in preventing and suppressing the development of adjuvant-induced arthritis.

Oxidative stress plays an important role in the progression of diabetes complications. The aim of the present study was to investigate the beneficial effect of oral administration of mangiferin in streptozotocin (STZ)-induced diabetic rats by measuring the oxidative indicators in liver and kidney as well as the ameliorative properties. Administration of mangiferin to diabetic rats significantly decreased blood glucose and increased plasma insulin levels. The activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) and level of reduced glutathione (GSH) were significantly (P < 0.05) decreased while increases in the levels of lipidperoxidation (LPO) markers were observed in liver and kidney tissues of diabetic control rats as compared to normal control rats. Oral treatment with mangiferin (40 mg/kg b.wt/day) for a period of 30 days showed significant ameliorative effects on all the biochemical and oxidative parameters studied. Diabetic rats treated with mangiferin restored almost normal architecture of liver and kidney tissues, which was confirmed by histopathological examination. These results indicated that mangiferin has potential ameliorative effects in addition to its antidiabetic effect in experimentally induced diabetic rats.

Sigma receptor antagonists diminish the effects of cocaine in behavioral assays, including conditioned place preference. Previous locomotor activity experiments in mice determined that the sigma receptor ligand YZ-185 (N-phenylpropyl-N'-(3-methoxyphenethyl)piperazine) enhanced cocaine-induced hyperactivity at a lower (0.1  μ mol/kg) dose and dose-dependently attenuated cocaine-induced hyperactivity at higher (3.16-31.6  μ mol/kg) doses. The present study investigated the effect of YZ-185 on cocaine's conditioned-rewarding properties in mice. YZ-185 (0.1, 0.316, 3.16, and 31.6  μ mol/kg) did not have intrinsic activity to produce conditioned place preference or aversion. A higher (31.6  μ mol/kg) YZ-185 dose, but not lower (0.1-3.16  μ mol/kg) YZ-185 doses, prevented the development of place preference to cocaine (66  μ mol/kg). YZ-185 did not alter the expression of cocaine place preference. To further characterize YZ-185's behavioral profile, its effects in the elevated zero maze and rotarod procedures were also determined; YZ-185 produced no significant change from baseline in either assay, indicating that the sigma receptors probed by YZ-185 do not regulate anxiety-like or coordinated motor skill behaviors. Overall, these results suggest that YZ-185 is a sigma receptor antagonist at the 31.6  μ mol/kg dose and demonstrate that sigma receptors can mediate the development of the conditioned-rewarding properties of cocaine.

The present study was performed as part of an attempt to authenticate the use of Inula racemosa root extract as traditional medicine in India by experimentally investigating their protective effects on 4-nitroquinoline-1-oxide (4-NQO) induced DNA damage and apoptosis in mice bone marrow cells. Aqueous root extract (ARE) of Inula racemosa (100, 200 and 400 mg/kg bw) with and without 4-NQO along with vehicle control (H2O) were administered orally for five consecutive days. 4-NQO (7.5 mg/kg bw) was injected intraperitoneally to the mice on the sixth day. After 24 h, the animals were sacrificed and extracted bone marrow cells were used for micronuclei and apoptotic analysis. Antiapoptotic effect of ARE (400 mg/kg bw) was measured by the use of Annexin V-FITC assay kit. 4-NQO generated the frequency of micronucleated polychromatic erythrocytes (MnPCEs) by about 4.7 times the control value, 14.29 MnPCEs/2500 PCEs. Pretreatment with ARE significantly reduced the MnPCEs frequency (39-72%) with respect to their doses, and increased PCEs/NCEs ratio was observed over the 4-NQO alone. 4-NQO-induced total apoptotic cells were about 12% over the control which was significantly (P < 0.05) brought down to 3.5% by pretreatment with 400 mg/kg bw of ARE. This was the first report that recorded the protective effects of I. racemosa on 4-NQO-induced DNA damage and apoptosis in mice bone marrow cells.

Antitussive effects of ethyl acetate fraction of Terminalia chebula on sulphur dioxide (SO2) gas induced cough have been examined in mice. Safety profile of Terminalia chebula was established by determining LD50 and acute neurotoxicity. The result showed that extract of Terminalia chebula dose dependently suppressed SO2 gas induced cough in mice. Terminalia chebula, after i.p. administration at dose level 500 mg/kg, offered maximum cough suppressive effects; that is, number of coughs at 60 min was 12 ± 1.52 (mean ± SEM) as compared to codeine 10 mg/kg; i.p., dextromethorphan 10 mg/kg; i.p., and saline, having frequency of cough 10.375 ± 0.866, 12.428 ± 0.81, and 46 ± 2.61, respectively. LD50 value of Terminalia chebula was approximately 1265 mg/kg, respectively. No sign of neural impairment was observed at antitussive doses of extract. Antitussive effect of Terminalia chebula was partly reversed with treatment by naloxone (3 mg/kg; s.c.) while rimcazole (3 mg/kg; s.c.) did not antagonize its cough suppression activity. This may suggest that opioid receptors partially contribute in antitussive action of Terminalia chebula. Along with this, the possibility of presence of single or multiple mechanisms activated by several different pharmacological actions (mainly anti-inflammatory, antioxidant, spasmolytic, antibacterial, and antiphlegmatic) could not be eliminated.

We previously reported that the apolipoprotein (apo) B48-carrying lipoproteins obtained from apoE knockout (apoE (-/-) ) mice, so called E(-)/B48 lipoproteins, transformed mouse macrophages into foam cells and enhanced the phosphorylation of eukaryotic translation initiation factor 2 α (eIF-2 α ). Furthermore, the eIF-2 α phosphorylation inhibitor, 2-aminopurine (2-AP), attenuated E(-)/B48 lipoprotein-induced foam cell formation. The present report studied the effect of 2-AP on atherosclerosis in apoE (-/-) mice. Our results showed that the level of food intake, bodyweight, plasma cholesterol, and triglycerides was comparable in apoE (-/-) mice treated with or without 2-AP. However, the mean size of atherosclerotic lesions in the aorta sinus as well as the surface area of the entire aorta of 2-AP-treated apoE (-/-) mice were reduced by about 55% and 39%, respectively, compared to samples from untreated control apoE (-/-) mice. In addition, the 2-AP-treated apoE (-/-) mice showed a significant decrease in glucose-regulated protein 78 (GRP78) and phosphorylated eIF-2 α in their aortic samples as compared to levels in untreated control apoE (-/-) mice. These observations suggest that endoplasmic reticulum stress is a causal mechanism for the development of atherosclerosis in apoE (-/-) mice and that therapeutic strategies can be developed for using eIF-2 α phosphorylation inhibitors, such as 2-AP, to prevent or treat atherosclerosis.

The present study aimed to investigate the protective effect of glycyrrhizin (locally isolated and purified from licorice root) against duck hepatitis virus through the assessment of some hematological and biochemical parameters. One hundred and sixty white Pekin ducklings-one day old-were randomly divided into four equal groups. Group (1) was kept as normal control. Group (2) was inoculated I/P with 10 mg glycyrrhizin/kg BW, three times per week for four weeks. Group (3) was inoculated I/M with 0.5 ml of live attenuated DHV vaccine. Group (4) was inoculated with both glycyrrhizin (10 mg/kg BW I/P, three times per week for four weeks) and live attenuated DHV vaccine (0.5 ml, I/M). Then, all groups of treatment were challenged using virulent DHV except for 20 ducklings from the normal control group which were continued to be kept as negative control. The results revealed that duck hepatitis virus (DHV) caused macrocytic hypochromic anemia, leukopenia, hypoproteinemia, hypoalbuminemia, hyperglycemia, hypercholesterolemia, and marked elevation of liver enzymes and renal parameters. In conclusion, glycyrrhizin injected alone or in combination with DHV vaccine protected or ameliorated the deteriorating effects induced by DHV vaccine and/or duck hepatitis virus infection by improvement of erythrogram and leukogram, as well as liver and kidney functions.

Heparin has been widely used as an anticoagulant for more than 80 years. However, there is now considerable evidence that heparin also possesses anti-inflammatory activity, both experimentally and clinically. Importantly in many instances, the anti-inflammatory actions of heparin are independent of anticoagulant activity raising the possibility of developing novel drugs based on heparin that retain the anti-inflammatory activity. Heparin exhibits anti-inflammatory activities via a variety of mechanisms including neutralization of cationic mediators, inhibition of adhesion molecules, and the inhibition of heparanase, all involved in leukocyte recruitment into tissues. It is anticipated that furthering our understanding of the anti-inflammatory actions of heparin will lead to the development of novel anti-inflammatory drugs for a variety of clinical indications.

The present study was undertaken to scientifically validate the antidiabetic activity of aqueous fruit extract of Trichosanthes dioica Roxb. (Family: Cucurbitaceae) which has been traditionally used for managing diabetes mellitus. This plant commonly known as "Sespadula" in English has not been explored scientifically so far for its glycemic potential except by our research group. The study was conducted with variable doses on normal, mild, and severe diabetics models, and several biochemical parameters including blood glucose level (BGL) were assessed. Maximum fall in BGL of 23.8% in normal rats and of 31.3% in mild diabetic rats was observed during their fasting blood glucose (FBG) and glucose tolerance test (GTT) with the dose of 1000 mg kg(-1). In severely diabetic animals after 4 weeks treatment with FBG, postprandial glucose, total cholesterol, and triglyceride levels were reduced by 28.7, 30.7, 57.2, and 18.5%, whereas high density lipoprotein, total protein, hemoglobin, and body weight were increased by 33.0, 36.7, 15.7 and 16.7%, respectively. Moreover, urine sugar was reduced from +4 to +1. Thus, the study scientifically validates the traditional use of T. diocia in diabetes management and could be developed as an effective oral agent for treating diabetes mellitus and complications associated with it.