Physiology and Pharmacology
Volume:18 Issue: 4, 2014

Ursolic Acid (UA) is a lipophilic triterpenoid compound, found in large amounts in apple peel. Anabolic effects of UA on the skeletal muscle and the role of this tissue as a key regulator of systematic aging aroused this question in mind whether UA might amend skeletal muscle performances such as myoglobin expression and also whether it switches skeletal muscle fibers from glycolytic to oxidative. In this study, 20 male C57BL/6 mice, aged 10 months, were used and divided to 2 groups. One group received UA (200 mg/kg) + corn oil as vehicle, and the other group was given only corn oil, intraperitoneally. Injection was done twice a day for 7 days, after which skeletal muscle was isolated and evaluated for myoglobin expression and fiber typing by western blotting and mATPase histochemistry techniques. UA caused myoglobin over-expression (p<0/01). It also changed anaerobic glycolytic muscle fibers into fast-oxidative (~ 30%) and slow-oxidative (4%) fibers. It seems that UA mimics beneficial effects of exercise through up-regulation of myoglobin expression and switching of muscle fiber types into oxidative fibers. It may be proposed as a good candidate for treatment of skeletal muscle dysfunction.

In this study, the effect of memantine administration into the nucleus accumbens on the metabolic changes induced by acute stress in female mice was evaluated. Intra-accumbens unilateral or bilateral canulation was performed. One week after recovery, a group of animals were given memantine (1, 0.5, and 0.1 μg/mouse) five min before stress induction intra-accumbally, and the other group received it (1, 0.5 and 0.1 mg/kg) 30 min before stress intraperitoneally. Food and water intake, weight of fecal material, and the delay time before eating were measured as metabolic parameters after stress induction. Acute stress reduced water and food intake, fecal matter, and the delay time before eating. Intraperitoneal memantine injections augmented the stress effect on water intake, but inhibited its effect on food intake at dose of 0.1 mg/kg and had no impact on defecation. The drug induced anorexia especially at dose of 1 mg/kg. On the other hand, intra-accumbens memantine injections reduced water intake when the drug was injected in the left side. Moreover, memantine injections inhibited or enhanced the effects of stress on water intake, food intake and defecation in a doseand location-dependent manner, and also increased the delay time before eating. Memantine inhibits or enhances the effects of acute stress dose-dependently. In addition, it seems that there is asymmetry in nucleus accumbens response.

Dopamine plays an important role in the central nervous system for modulating food intake. Dopamine receptors are distributed within the hypothalamus, and expression of D1 receptors is significant in hypothalamic paraventricular nucleus (PVN). Therefore, the aim of this study was to find if PVN-microinjected SKF38393, D1 receptor agonist, may modulate food intake. Guide cannula directed to the PVN were implanted in male Wistar rats (220-250 g). Stereotaxic coordinates were: lateral: +0.4 mm from midline; dorsoventral: 7 mm from skull surface; anteroposterior: -1.8 mm from the bregma. Intra-PVN microinjections of SKF38393, SCH23390 (D1 receptor antagonist) and saline were performed after a 5-7 day recovery period. Hourly over a 3 hours period, the weight of food pellets was measured. Assessment of spontaneous activity in rat was performed in standard activity chambers interfaced with a Digiscan animal. Feeding trials were done normally from Saturday to Wednesday between 9:00 am and 12:00 on rats which were deprived of food for 24 hours. All drugs were administered in 0.9% saline. Intraparaventricular injections of SKF38393 (0.06, 0.01 μg) decreased food intake in a dose-dependent manner. The PVN injection of SCH23390, D1 receptor antagonist, did not affect food intake decreased by PVNmicroinjected SKF38393 (0.01 μg). Analysis of the physical activity revealed that PVN microinjection of SKF38393 (0.01 μg) did not affect locomotor activity. Our results showed that PVN-microinjected SKF38393 decreases food intake. This suppressive effect is probably not mediated through D1 receptors.

The ginger rhizome has been widely used in traditional medicine for treatment of gastrointestinal diseases. In the present study the effect of ginger alcoholic extract on mechanical activity of isolated jejunum of male rats and also its interaction with cholinergic, adrenergic and Nitrergic systems were investigated. Seven adult male Wistar rats were anesthetized by ethyl ether, their abdomen opened, and jejunum dissected and divided into 1 cm strips. The strips were divided to experimental and control groups, and placed in organ baths containing oxygenated, 37˚C, pH=7.4 Tyrode’s solution connected to a force transducer which was linked to AD Instrument power lab. In the experimental group, 0.475 mg/mL alcoholic ginger extract and in the control group solvent was added to the organ bath. Then mechanical activity of the strips in each group was recorded before and after administration of acetyl choline (as cholinergic agonist), phenylephrine (as α-adrenergic agonist), isoproterenol (as β- adrenergic agonist), propranolol (as β-adrenergic antagonist) and L-NAME (as nitric oxide synthase blocker). Data were statistically analyzed using SPSS and independent-sample t-test at P≤0.05 as significance level. A significant (p<0.05) decrease in mechanical activity was found after administration of alcoholic ginger extract compared with the control group, which was not reversed after acetyl choline administration. Also, no change was detected after administration of phenylephrine, isoproterenol, propranolol and L-NAME. This study showed that alcoholic extract of ginger has modifying effect on intestinal motility that is partly related to the cholinergic system and possibly independent of the adrenergic and nitrergic systems.

Artemisia dracunculus L. belongs to Asteraceae family, and is a medicinal plant widely used in traditional medicine as a remedy for gastrointestinal disturbances. This study was undertaken to evaluate the effects of essential oil of A. dracunculus (EOAD) on the rat alimentary tract. The EOAD was extracted by Clevenger apparatus using hydrodistillation. LD50 was calculated based on the Lorke’s method. The effects of EOAD (50–125 mg/kg) on intestinal transit time and diarrhea were investigated in adult Wistar rats. EOAD was administered via oral route. For antidiarrheal effect evaluation, castor oil (2 mL/rat) was administered intragastrically 30 min after EOAD (50-100 mg/kg) treatments and loperamide (3 mg/kg). The rat cages were inspected hourly up to 4 hours for the presence of the characteristic diarrheal droppings, start time of diarrhea, weight of stool, and the number of stool plates. The LD50 was 707.10 mg/kg. EOAD significantly inhibited intestinal motility at 125 mg/kg dose (P<0.05). EO inhibitory effect was significantly (P<0.05) enhanced with simultaneous atropine. Castor oil caused diarrhea in all animals in the control group in 93.83± 4.81 min. EOAD inhibited the castor oil-induced diarrhea at 75 and 100 mg/kg doses. The EOAD delayed the onset of diarrhea, and produced a significant decrease in the frequency of defecation as well as severity of diarrhea. It also protected the rats against diarrhea. In comparison with loperamid, the reference antidiarrheal agent, the higher dose of EOAD demonstrated the same effective protection as castor oil-induced diarrhoea. These primary data indicated that the plant contains antidiarrheal constituents, which support the popular therapeutic use of A. dracunculus for gastrointestinal disorders in traditional medicine.

Controlling parenchymal hemorrhage, especially in liver, is still one of the challenges surgeons face with when they try to save the patients’ lives despite improvements in surgical procedures. There is a research contest between the researchers in this field to introduce more effective methods. This study aimed to compare the hemostatic effect of ferric sulfate and ferric chloride on controlling the bleeding from liver parenchymal tissue. In this animal model study 70 male Wistar rats were randomly allocated into seven groups. An incision, 2 cm long and 0.5 cm deep, was made on each rat’s liver, and the hemostasis time was measured with different concentrations (15%, 25%, and 50%) of either ferric sulfate or ferric chloride compared with the control method (i.e. by simple suturing). The liver tissue was examined for pathological changes after one week. The obtained data were analyzed using Kruskal-Wallis, Mann-Whitney, and Kolmogorov-Smirnov tests in the SPSS software. We found complete hemostasis in all groups. The hemostasis times of different concentrations of ferric sulfate and ferric chloride were significantly less than that of the control group (P value<0.01). Ferric sulfate showed statistically significant faster hemostasis at different concentrations compared with ferric chloride (P value<0.01). Ferric sulfate and ferric chloride need less time to control liver bleeding compared to the control method (i.e. by sutures). Ferric sulfate is a more effective hemostatic agent than ferric chloride in controlling hepatic bleeding in an animal model.

Renin angiotensin system has an important role in blood pressure and renal functions. Active angiotensin-converting enzyme 2 converts angiotensin I into angiotensin-(1-7) which is a vasodilator hormone and interacts with nitric oxide changes as well as other angiotensin II receptors. In this study we evaluated the role of Mas receptor antagonist (A779) and renal perfusion pressure (RPP) on serum nitric oxide metabolite (nitrite) concentration when angiotensin II receptors (AT1R & AT2R) were blocked. After angiotensin II receptors blockage in anesthetized male and female rats, RPP was maintained at two levels 80 & 100 mmHg by occluder around aorta above the renal arteries, and the effects of placebo and A779 on concentration of serum nitrite level were studied. The results showed that when angiotensin II receptors were blocked, the serum level of nitrite in both sexes, was not dependent on angiotensin-(1-7) receptor and did not change statistically, but by increasing renal perfusion pressure and in the presence of angiotensin-(1-7) receptor the serum level of nitrite increased significantly (p<0.05) in male rats but not in female rats. Using angiotensin II receptors blockades and by increase of RPP, the serum level of nitrite is sexrelated. This study showed the importance of Mas receptor in male sex when AT1R & AT2R were blocked.

The aim of the present study was to evaluate the effect of exercise training and L-arginine supplementation on oxidative stress and systolic ventricular function in rats with myocardial infarction (MI). Four weeks after the surgically-induced MI, 40 male Wistar rats were randomly assigned to the following 4 groups (n=10): MI-sedentary control (Sed); MI-exercise (Ex); MI-sedentary+L-arginine (Sed+LA); and MIexercise+ L-arginine (Ex+LA). The Ex and Ex+LA groups ran for 10 weeks on treadmill. Rats in the L-arginine-treated groups drank water containing 4% L-arginine. Before and after the training program, all subjects underwent resting echocardiography. Also catalase, glutathione peroxidase, malondialdehyde and myeloperoxidase were measured. cardiac output, stroke volume and fractional shortening in Ex and Ex+LA groups were significantly increased compared to the Sed group. Cardiac systolic function in Ex+LA group was significantly greater than in Ex group. Infarct size was insignificantly reduced in response to exercise. Also, glutathione peroxidase activity was increased while malondialdehyde showed a decrease in response to exercise training, but no effect on myeloperoxidase and catalase was noted. There was no difference in enzyme activity between the training groups. Exercise training increased LV systolic function by decreasing oxidative stress and increasing antioxidant defense system in rats with myocardial infarction. It appears that L-arginine improves left ventricular function, but has no effect on oxidative stress indices.

17β-estradiol modulates nociception by binding to estrogenic receptors and also by allosteric interaction with other membrane-bound receptors like glutamate and GABAA receptors. Beside its autonomic functions, paragigantocellularis lateralis (LPGi) nucleus is also involved in pain modulation. The aim of the current study was to investigate the role of the intracellular estrogenic receptors in the pain modulation by the LPGi nucleus of male rats. In this study, male Wistar rats in the range of 200-270 gr were used. In order to study the effect of intra- LPGi microinjection of 17β-estradiol on both acute and persistent pain modulation, cannulation of LPGi nucleus was performed. At first, drugs were injected and 15 minutes later 50 μl of 4% formalin was injected into the rat's hind paw. Then formalin-induced flexing and licking behaviours were recorded for 60 min. The results of current study showed that intra-LPGi injection of 17β-estradiol attenuated the flexing and the licking behaviours both in the first phase (P<0.01) and in the second phase (P<0.001) of formalin test. The estrogen receptor antagonist (ICI182,780) prevented 17β-estradiol-induced analgesic effect but could not reverse this effect to the control condition, and it had significant difference with the control group, yet. It may be concluded some part of the analgesic effect of 17β-estradiol in the LPGi nucleus on the formalin-induced inflammatory pain is probably mediated by estrogenic receptors.

Neuropathic pain is one of the common complications of diabetes mellitus which is caused by impairment in nerve conductivity. The role of flavonoid and polyphenol compounds in treatment of neuropathic pain has been revealed، and extract of onion contains significant amounts of these compounds. The aim of this study was to investigate the effect of alcoholic extract of onion on diabetic neuropathic pain in streptozotocin-diabetic rats. In this experimental study، 40 male Wistar rats were divided into 5 groups: normal control، diabetic control and groups receiving alcoholic extract of onion (125، 250 and 500 mg/kg/day). After injection of streptozotocin (55 mg/kg)، the extract was administered for 3 weeks. At days 0، 7، 14 and 21 after injection of streptozotocin، assessment of neuropathic pain was performed by thermal allodynia، mechanical allodynia، hyperalgesia and formalin test. Behavioral responses to thermal and mechanical stimuli in diabetic control rats showed significant reduction (P<0. 05). Oral administration of alcoholic extract of onion at doses of 125 and 250 led to improvement in diabetic neuropathic pain in all 4 tests. However، dose of 500 mg didn’t improve neuropathic pain. Oral administration of alcoholic extract of Iranian red onion improves diabetic neuropathic pain in rats.

Olibanum improves memory in different models of learning. However, the effect of olibanum on models of Alzheimer’s disease has been less studied. In the present study, the effect of olibanum on memory in normal rats and in a rat model of Alzheimer disease induced by intracerebroventricular injections of streptozotocin was evaluated. Rats received an aqueous extract of olibanum (50, 100 and 300 mg/kg) via gavage, acutely 30 minutes before the test and chronically for 21 consecutive days before assessment of memory racall. In two other groups of animals, two guide cannulas were inserted into the lateral ventricles under stereotaxic surgery. One group received bilateral injections of streptozotocin (1.5 mg/kg/2 μl/side) in the first and third days of surgery. The other group received artificial cerebrospinal fluid. Fourteen days after surgery, learning was evaluated. Two other groups of animals received olibanum (50 mg/kg) or its solvent, for 21 days beginning from one week before injections of streptozotocin. Acute administration of olibanum did not affect learning parameters, but chronic administration of it (50 mg/kg) improved memory retrieval. Streptozotocin increased number of necessary stimulations for induction of short term memory, but decreased step through latency, significantly. In animals which received streptozotocin, olibanum increased step through latency, significantly. Olibanum reduces the risk of Alzheimer’s disease induced by streptozotocin. Further studies with emphasis on active constituents of olibanum may result in development of drugs capable of decreasing probability of Alzheimer’s disease occurrence.