Analgesic and antiinflammatory activities of the essential oil from Artemisia sieberi Besser

The analgesic activity of Artemisia sieberi oil was assessed by acetic acid-induced writhing test and Eddy’s hot plate method; while the acute anti-inflammatory effect was investigated by inflammatory paw edema test in rats. The administration rout of the essential oil, standard drugs and the vehicle used in all assays was intraperitoneal injection. The 1 and 2.5 mg/kg doses of the studied oil significantly decreased the number of acetic acid-induced writhes in mice. The dose of 1 mg/kg of the oil also exhibited a central analgesic effect as evidenced by a significant increase in reaction time at several time points after 15 min treatment in the hot plate method. In addition, the 1 mg/kg dose of the oil significantly reduced carrageenan induced paw edema in rats at the first hour of the test by 72.7% inhibition and lasted to the third hour of the test by 74.3% inhibition found to be very close to that of the standard drug, diclofenac sodium (50 mg/kg). The major components of the oil were characterized as camphor (31.2%) and 1,8-cineole (20.0%). The results suggest that A. sieberi essential oil has a significant effect against acute inflammation and has central and peripheral anti-nociceptive effects

The Possible Role of Nitric Oxide and Oxidative Stress in the Enhanced Apoptosis of Cardiac Cells in Cirrhotic Rats

Abstract- Cirrhosis has been related with hyperdynamic circulation, manifesting as increased cardiac output and decreased systemic vascular resistance. In the present study we examined the cirrhosis outcome on apoptosis of rat hearts. We also tried to explore the role of nitric oxide (NO) and oxidative stress in the probable changed apoptosis of cirrhotic hearts. Twenty eight days after ligation of bile duct, heart tissues were tested for apoptosis. The extent of malondialdehyde (MDA), and the activities of catalase (CAT), glutathione peroxidase (GSHPx) and superoxide dismutase (SOD) have been calculated in heart tissues. The cirrhotic hearts exhibited structural defects and greater apoptosis. Chronic treatment of cirrhotic rats with LNAME, a non-selective inhibitor of NO synthase, inhibited heart structural defects and reduced apoptosis of hearts. We also showed that cirrhotic rat hearts had an enhanced level of MDA and reduced activities of CAT, GSHPx and SOD. When the animals were treated by L-NAME chronically, the MDA level reduced and activities of CAT, GSHPx and SOD augmented in cirrhotic heart. In conclusion, increased apoptosis of cirrhotic hearts probably happen due to NO overproduction and increased oxidative stress in hearts of cirrhotic rats

The Possible Role of Nitric Oxide and Oxidative Stress in the Enhanced Apoptosis of Cardiac Cells in Cirrhotic Rats

Abstract- Cirrhosis has been related with hyperdynamic circulation, manifesting as increased cardiac output and decreased systemic vascular resistance. In the present study we examined the cirrhosis outcome on apoptosis of rat hearts. We also tried to explore the role of nitric oxide (NO) and oxidative stress in the probable changed apoptosis of cirrhotic hearts. Twenty eight days after ligation of bile duct, heart tissues were tested for apoptosis. The extent of malondialdehyde (MDA), and the activities of catalase (CAT), glutathione peroxidase (GSHPx) and superoxide dismutase (SOD) have been calculated in heart tissues. The cirrhotic hearts exhibited structural defects and greater apoptosis. Chronic treatment of cirrhotic rats with LNAME, a non-selective inhibitor of NO synthase, inhibited heart structural defects and reduced apoptosis of hearts. We also showed that cirrhotic rat hearts had an enhanced level of MDA and reduced activities of CAT, GSHPx and SOD. When the animals were treated by L-NAME chronically, the MDA level reduced and activities of CAT, GSHPx and SOD augmented in cirrhotic heart. In conclusion, increased apoptosis of cirrhotic hearts probably happen due to NO overproduction and increased oxidative stress in hearts of cirrhotic rats

Activation of cannabinoid receptors elicits antidepressant-like effects in a mouse model of social isolation stress

Social isolation stress (SIS) paradigm is a chronic stress procedure able to induce profound behavioral and neurochemical changes in rodents and evokes depressive and anxiety-like behaviors. Recent studies demonstrated that the cannabinoid system plays a key role in behavioral abnormalities such as depression through different pathways; however, there is no evidence showing a relation between SIS and the cannabinoid system. This study investigated the role of the cannabinoid system in depressive-like behavior and anxiety-like behavior of IC animals. For this purpose, NMRI mice were treated with WIN55, 212-2 (non-selective cannabinoid receptor agonist) and AM-251 (cannabinoid receptor type 1 antagonist) and AM-630 (cannabinoid receptor type 2 antagonist). We found that behavioral abnormality followed by SIS was mitigated after administration of WIN55, 212-2. Also, depressive-like effects induced by SIS were significantly increased following administration of AM-251 and AM-630. Co-administration of cannabinoid receptor antagonists (AM-251 and AM-630), significantly reversed the antidepressant effect of WIN55, 212-2 in IC animals. Our findings suggest that the cannabinoid system is involved in depressive-like behaviors induced by SIS. We showed that activation of cannabinoid receptors (type 1 and 2) could mitigate depression-like behavior induced by SIS in a mouse model

Novel derivatives of phthalimide with potent anticonvulsant activity in PTZ and MES seizure models

Objective(s): Phthalimide-based derivatives have anticonvulsant activity like as phenytoin by inhibition of sodium channel. In our previously research we mentioned about some phthalimide derivatives as potent anticonvulsant agents. Materials and Methods: Fourteen analogs of 2-substituted phthalimide pharmacophore were synthesized and then were evaluated for the anticonvulsant activities in pentylenetetrazole-induced seizures (PTZ) and maximal electroshock seizure (MES) models. Results: The in vivo screening results showed that all the analogs have the ability to protect against the maximal electroshock and PTZ. The compounds 3 and 9 elevated clonic seizure thresholds at 30 min which were more active than the standard medicine phenytoin. Compounds 3, 6, 7, 11, 13 and 14 with 100% protection were the most potent ones in tonic seizure. The most potent compound in the both PTZ and MES models was compound 3. Using a model of the open pore of sodium channel, all of the compounds were docked. Results of docking showed that the ligands interacted mainly with residues II-S6 of NaV1.2 by making hydrogen bonds and have additional hydrophobic interactions with other domains in the channel's inner pore. Conclusion: Some of these compounds are more potent than phenytoin simultaneously in the clonic and tonic seizures

Antioxidant Potential, Hypoglycemic Effect and Safety of Ajuga chamaecistus Ging. ssp. tomentella (Boiss.) Rech. f. Aerial Parts

Background and objective: Ajuga species(Lamiaceae) are traditionally used in the treatment of jaundice, joint pain, sciatic nerve, and diabetes in different countries. The aim of this study was to investigate the antioxidant and hypoglycemic activities and safety of Ajuga chamaecistus ssp. tomentella. Methods: Antioxidant activity, radical scavenging effect, and total phenolics content of the aqueous and methanol extracts were assessed using ferric reducing antioxidant power (FRAP), 2, 2-diphenyl-1-picryl-hydrazyl (DPPH) radical scavenging and Folin-Ciocalteu methods. Streptozotocin (STZ) induced diabetic mice were studied in separate groups comprising aqueous and methanol extracts (200, 400, 800 mg/kg), metformin (500 mg/kg) and a negative control group. Results: The n-butanol fraction showed the most phenolics content (26.5 mg GAE/g of extract) and the highest antioxidant power) 346.7 mmol FeІІ/g of extract) as well as the most considerable radical scavenging activity (IC50=15.34 µg/mL). In STZ-diabetic mice, repeated oral administration of all doses of extracts showed a significant decrease in plasma glucose levels after 3, 14 and 28 days. The results of acute toxicity study showed that the ethanol extract was non-toxic up to the dose of 6000 mg/kg. Based on the sub-chronic toxicity results, a significant decrease in cholesterol and triglyceride was observed after using the extract (1000 mg/kg) for 23rd and 45th days. Histopathology of animal tissues revealed no significant differences in animal tissues between treated and control groups after 23 and 45 days. Conclusion: our study indicated the antioxidant potential, safety and hypoglycemic effect of A. chamaecistus ssp. tomentella extracts

Lead poisoning in opium-addicted subjects, its correlation with pyrimidine 5′-nucleotidase activity and liver function tests

Background: Lead may be added to the opium by drug smugglers. It can cause elevated blood lead level (BLL) in opium-addicted patients. Erythrocyte pyrimidine 5′-nucleotidase (P5N) activity is susceptible to high BLL. The aim of this study was to find out whether opium-addicted patients show erythropathy and elevated liver enzymes explainable by high BLL and decreased P5N activity. Methods: Forty orally opium-addicted subjects and 40 normal healthy volunteers were enrolled in this study. BLL was measured in whole blood specimens using atomic absorption spectrometry instrumentation. Enzymatic activity, protein amount of P5N, and erythrocyte purine/pyrimidine ratio were determined. Blood films were analyzed for the presence of basophilic stippling of red cells and hemolytic anemia. The level of liver function enzymes was measured. Results: The mean BLL for opium-addicted patients was significantly higher than control group (P < 0.001). On the contrary, P5N activity showed a valid decrease in opium-addicted patients when compared with control group (P < 0.001). In line with repressed P5N activity, erythrocyte purine/pyrimidine ratio in patients was lower than control group (P < 0.001). A statistically significant reverse correlation was found between BLL and P5N activity (P < 0.05, r = −0.85). The prevalence of both basophilic stippling (P < 0.001, z = 6.62) and hemolytic anemia (P < 0.001, z = 6.52) in study population was significantly associated with elevated BLL. We could not find any significant correlation between serum level of liver enzymes and BLL. Conclusions: Opium-addicted patients in Tehran, Iran, are at high risk of lead poisoning which may result in hematologic problems and possibly hepatic damage

A Direct Comparison of Anti-ulcer Effects of Coenzyme Q10 and Vitamin C on Indomethacin-induced Gastric Ulcer in Rat: A Controlled Experimental Study

Introduction: Indomethacin increases generation of mitochondrial reactive oxygen species (ROS) which have a crucial role in the indomethacin-induced gastric ulcer. Coenzyme Q10 has an antioxidant activity on mitochondria and cell membranes and protects lipids from oxidation and is essential for stabilizing biological membranes. Superoxide dismutase (SOD) acts as one of the defense mechanisms against free radicals. When the generation of ROS overwhelms, the antioxidant defense, lipid peroxiation of cell membrane occurs and cause cell damage. Materials and Methods: Male adult Wistar rats were divided into A and B groups. The rats in group A were then further divided into three subgroups of 6 animals each and received one of the following treatments: Animals in the first subgroup received saline. Animals in the second subgroup received saline and indomethacin. Animals in the third subgroup received vitamin C and indomethacin. The rats in group B were also further divided into 3 subgroups of 6 rats each and treated with one of the following treatments: Animals in first subgroup received 1% Tween 80 as vehicle. Animals In second subgroup received 1% Tween 80 and indomethacin. Animals in third subgroup received CoQ10 and indomethacin. Four hours after the last treatment, animals were killed and the stomachs removed were cut and gastric mucosal lesions were examined). Ulcer indexes were determined and SOD activity measured in plasma                                                             Results: Pretreatment with both vitamin C and coenzyme Q10 was associated with attenuation of ulcer index and increased SOD activity compared with animals treated with indomethacin alone (

Tyramine, a biogenic agent in cheese: amount and factors affecting its formation, a systematic review

Abstract Tyramine is one of the most important biological amines in food, which leads to food poisoning if consumed in high amounts. In addition to food poisoning, tyramine leads to drug interactions. Foods high in tyramine can cause high blood pressure and migraines in people taking monoamine oxidase (MAO) inhibitors. Therefore, people taking MAO inhibitors should avoid foods high in tyramine. Cheese provides ideal conditions for the production of tyramine. Some cheeses contain high amounts of tyramine and lead to unwanted effects in people taking MAO inhibitors. These unwanted effects are called the cheese effect or tyramine interaction. Considering the importance of the subject, a systematic study was designed with the aim of determining the amount of tyramine in cheeses and the effect of effective factors on the amount of tyramine production. The search was done in three databases, including Scopus, PubMed, and Science Direct. The study was conducted in two phases. In the first stage, the amount of tyramine reported in cheeses, the analytical method, measurement, and characteristics of cheese were discussed. In the second phase, the influencing factors in its formation were investigated. Based on the extracted data, tyramine levels ranged from 3.23 to 1398 mg/kg. The most analytical method for measuring tyramine in the studies was the HPLC method. According to a detailed review of the literature, the influencing factors included bacterial species, animal species, the effect of storage conditions (time and temperature), pH, moisture, salt, and the number of somatic cells. Basically, by identifying the factors affecting the amount of tyramine in cheeses, it is possible to control the production of tyramine. Graphical Abstrac

The Effects of Sub-Chronic Treatment with Pioglitazone on the Septic Mice Mortality in the Model of Cecal Ligation and Puncture: Involvement of Nitric Oxide Pathway

Sepsis is a systemic inflammatory response syndrome caused by an infection and remains as a major challenge in health care. Many studies have reported that pioglitazone may display anti-inflammatory effects. This study was designed to evaluate the effect of subchronic treatment with pioglitazone on high-grade septic mice survival and nitrergic system involvement. Diffused sepsis was induced by cecal ligation and puncture (CLP) surgery in male NMRI mice (20-30 g). Pioglitazone (5,10 and 20 mg/kg) was administered by gavage daily for 5 days prior to surgery. Nitric oxide involvement was assessed by sub-chronic administration of a non-selective nitric oxide synthase inhibitor, L-NAME and a selective inducible nitric oxide synthase inhibitor, aminoguanidine. TNF-α  and IL-1β plasma levels were measured by ELISA. Pioglitazone (10 and 20 mg/kg) significantly improved survival rate in septic mice. The chronic intraperitoneally co-administration of L-NAME (0.5 mg/kg, daily) or aminoguanidine (1 mg/kg, daily) with a daily dose of pioglitazone, 5 mg/kg, significantly increased the survival rate. This survival improving effect was accompanied by a significant reduction in pro-inflammatory cytokines TNF-α and IL-1β plasma levels. In conclusion, sub-chronic pioglitazone treatment can improve survival in mouse sepsis model by CLP. Inhibition of nitric oxide release, probably through inducible nitric oxide synthase at least in part is responsible for this effect. Suppression of TNF-α and IL-1β could be another mechanism in pioglitazone-induced survival improving effect in septic mice