Protective effects of gallic acid against chronic cerebral hypoperfusion-induced cognitive deficit and brain oxidative damage in rats

Free radical induced neural damage is implicated in cerebral hypoperfusion disorders and antioxidants have protective effects. In the present study, we examined the effect of gallic acid (GA; 100 mg/kg, p.o. for 10 days) on cognitive deficit and cerebral oxidative stress induced by permanent bilateral common carotid artery occlusion (2VO) as an animal model of vascular dementia (VD). The results showed that 2VO significantly reduced the spatial memory performance in Morris water maze as well as non enzymatic (total thiol) and enzymatic glutathione peroxidase (GPx)] antioxidant contents and increased the level of malondialclehyde (MDA) in the hippocampus and frontal cortex of vehicle-treated group as compared to sham-operated rats. Furthermore, chronic administration of GA significantly restored the spatial memory, total thiol and GPx contents and also decreased MDA levels in these tissues. GA alone did not show any change neither in the status of various antioxidants nor behavioral tests over sham values. The results demonstrate that GA has beneficial activity against 2VO-induced cognitive deficits via enhancement of cerebral antioxidant defense. Taken together, the present study suggested that GA might be useful in the treatment of VD. (C) 2014 Elsevier B.V. All rights reserved

Sesamin alleviates defects in seizure, behavioral symptoms, and hippocampus electroencephalogram in a pentylenetetrazol rat model

Objective(s): Seizure is a prevalent disorder reflected by powerful and sudden activity of neural networks in the brain that leads to tonic-clonic attacks. These signs may be due to an increase in excitatory/inhibitory neurotransmitters ratio. So, the current experiment aimed to examine the seizure and neurobehavioral parameters, as well as the hippocampus local electroencephalogram (EEG) after seizure with and without sesamin pretreatment.   Materials and Methods: Sesamin (15, 30, and 60 mg/kg/5 ml, intraperitoneal or IP, vehicle: dimethyl sulfoxide or DMSO, for 3 days) was administrated before pentylenetetrazol (PTZ) (60 mg/kg/10 ml, IP, vehicle: saline), which induces acute seizure in adult male Wistar rats (230 ± 20 g, six weeks old). Different phases of seizures (score, latency, duration, and frequency), behavioral parameters (passive avoidance memory, anxiety, and locomotor activity), and hippocampus local EEG were evaluated after the injections. At the end of the experiments, oxidative stress markers plus gene expression of phosphoinositide 3-kinase/protein kinase B or PI3K/Akt mRNA were measured in the hippocampus.  Results: Pretreatment with sesamin (30 mg/kg) could significantly decrease seizure scores and oxidative stress in the hippocampus. PTZ injection induced EEG deficits and neurobehavioral impairments which were significantly decreased by sesamin, especially in Beta, Theta, and delta EEG waves.  Also, the expression of PI3K/Akt significantly increased in the sesamin (30 mg/kg) group in comparison with the PTZ group. Conclusion: Sesamin could prevent seizure attacks and neurobehavioral and EEG deficits induced by pentylenetetrazol, probably through the PI3K/Akt signaling pathway

Gallic acid improves cognitive, hippocampal long-term potentiation deficits and brain damage induced by chronic cerebral hypoperfusion in rats

Cerebral Hypoperfusion Ischemia (CHI) has important role in neuronal damage and behavioral deficits, including memory and Long-term Potentiation (LTP) impairment. Protective effects of Gallic Acid (GA) on memory, hippocampus LTP and cell viability were examined in permanent bilateral common carotid artery occlusion in rats. Animals were divided into 9 groups: Control (Cont); sham operated (Sho); Cerebral Hypoperfusion Ischemia (CHI); CHI received normal saline (CHI +Veh); CHI treated with different doses gallic acid (50,100, 200 mg kg-1 for 5 days before and 5 days after CHI induction, orally); CHI treated with phenytoin (50 mg kg-1, ip) (CHI+Phe); and sham operated received 100 mg kg-1, orally (Sho+GAl 00). CHI was induced by bilateral common carotid artery occlusion (2VO). Behavioral, electrophysiological and histological evaluations were performed. Data were analyzed by one-way and repeated measures ANOVA followed by tukey's post-hoc test. GA improved passive avoidance memory, hippocampal LTP and cell viability in hippocampus and cortex of ischemic rats significantly (p<0.01). The results suggest that gallic acid via its antioxidative and free radicals scavenging properties attenuates CHI induced behavioral and electrophysiological deficits and has significant protective effect on brain cell viability. Dose of 100 mg kg-1 GA has affected the ischemic but not intact rats and its effect was more potent significantly than phenytoin, a routine drug for ischemic subjects. © 2014 Asian Network for Scientific Information

Ameliorative Effect of Vanillic Acid on Serum Bilirubin, Chronotropic and Dromotropic Properties in the Cholestasis-Induced Model Rats

Introduction: The liver modulates several important roles, such as metabolism and liver cirrhosis, which have several cardiovascular problems. Due to preservative role of antioxidant agents in cardiovascular disease, consequently, many of them are applied as medicinal plants in traditional medicine. Vanillic acid (VA), as an antioxidant agent, has a principal preservative role on some diseases. In this study, the effect of vanillic acid was examined on heart rate (as chronotropic property), P-R interval (as dromotropic property), and serum bilirubin in cholestasis-induced model rats. Methods: In this study, 32 male Sprague-Dawley rats weighing 200-250 g were allocated into four groups, and each group contained eight rats as follows: Control (normal saline, 1 ml/kg, gavage, daily for 4 weeks), cirrhotic (normal saline, 1 ml/kg, gavage, daily for 4 weeks), vanillic acid (10 mg/kg, gavage, daily for 4 weeks), cirrhotic treated with vanillic acid (10 mg/kg, gavage, daily for 4 weeks). Chronic biliary cirrhosis was induced in cirrhotic groups by four weeks Bile Duct Ligation (BDL). At the first day and four weeks after surgery, the animals were anesthetized, electrocardiograms were recorded (lead II), and chronotropic and dromotropic properties (HR and PR interval) were investigated. At the end of experimental duration, the animals were anesthetized, and blood samples were taken to measure serum bilirubin. The results were analyzed using t-test and one-way ANOVA by SPSS software, version 22. Results: After induced of BDL, the results presented that laboratory parameter (bilirubin) in the cirrhotic group significantly increased compared to the control group. The P-R interval was reduced in the cirrhotic group compared to the control group, and there was no significant difference between heart rate in all groups. Bilirubin were reduced in cirrhotic groups treated with vanillic acid (VA) compared to cirrhotic group and also administration of VA in the cirrhotic treated with VA increased dromotropic property in comparison with the cirrhotic group. Conclusion: According to the results obtained in this study, preventing elevated bilirubin and increase dromotropic property in cirrhotic group taking the VA suggested that the consumption of vanillic acid as an antioxidant can be effective in the prevention of liver diseases

Antidiabetic effect of honey feeding in noise induced hyperglycemic rat: involvement of oxidative stress

Objective(s):In this study the effect of oral administration of honey on serum glucose, lipids, stress oxidative markers, and morphology of langerhans islets in noise induced hyperglycemic rats was investigated. Materials and Methods: Male Wistar rats were divided into control, hyperglycemic, honey treated control, and honey treated hyperglycemic groups. For induction of hyperglycemia, noise stress was used. Serum glucose, triglyceride (TG), total cholesterol, low density lipoprotein (LDL), and high density lipoprotein (HDL)-cholesterol levels were determined before the study and at 4th and 8th weeks after the study. Markers of oxidative stress in brain were also measured. Morphology of langerhans islets in four groups was evaluated using Gomori staining method. Results: Treatment of noise induced hyperglycemic rats with honey produced a hypoglycemic effect and appropriate changes regarding serum lipids in treated diabetic group at 4th and 8th weeks as compared to the control group. Meanwhile, honey treatment significantly ameliorated the increased malondialdehyde (MDA) content and reduced the activity of superoxide dismutase (SOD) in brain. Histology of langerhans islets in hyperglycemic group showed a lower number and granularity of beta cells; honey treatment produced beneficial change in this respect. Conclusion: Oral administration of honey in experimental model of diabetes showed a significant hypoglycemic effect and led to appropriate changes in serum lipid profiles

Improving Active and Passive Avoidance Memories Deficits Due to Permanent Cerebral Ischemia by Pomegranate Seed Extract in Female Rats

Background: This study aimed to evaluate the effect of two weeks oral administration of pomegranate seed extract (PGSE) on active and passive avoidance memories after permanent bilateral common carotid arteries occlusion (2CCAO) to induce permanent cerebral ischemia in adult female rats. Methods: Seventy adult female Wistar rats (250 ± 20 g) were used. Animals were divided randomly into seven groups with 10 in each: 1) Sham-operated; 2) Ischemic; 3–6) Ischemic received PGSE (100, 200, 400, and 800 mg/2mL/kg, orally) for 14 days; 7) Ischemic received vehicle. In order to create 2CCAO, carotid arteries were ligatured and then cut bilaterally. Active and passive avoidance task were measured using criterion condition responses (CCRs) in Y-maze and step-through latency (STL) in two-way shuttle box in all female rats. Results: Both active and passive avoidance memories were significantly impaired in rats after cerebral hypoxia-ischemia (CHI) (P < 0.001). PGSE treatment significantly improved passive and active memory impairments with 2CCAO (P < 0.05, P < 0.01, and P < 0.001). No toxicity was observed even with high-dose PGSE consumption (800 mg/kg, for 14 days). Conclusion: PGSE exhibits therapeutic potential for avoidance memories, which is most likely related at least in part to its antioxidative and free radical scavenging actions

The effects of olive leaf extract and 28 days forced treadmill exercise on electrocardiographic parameters in rats

Background: There is evidence that regular activity can prevent of cardiovascular diseases. There are many reports that exercise and the consumption of olive leaf extract (OLE) have a positive effect on cardiovascular parameters. This study was conducted to compare the effects of exercise and OLE alone and together on electrocardiographic parameters in rats. Materials and Methods: Male Sprague–Dawley rats were randomly divided into six groups (n = 8 rats in each): Control, exercise, OLE (100, 200, and 400 mg/kg, orally for 14 days), and exercise + OLE (200 mg/kg of extract, orally for 14 days). Exercise training in rats was performed using treadmill for 28 days (1 h/day). Electrophysiological parameters including heart rate, PR interval, QT interval, QT corrected (QTc), RR interval, QRS voltage, and duration were obtained from lead II electrocardiogram (ECG) recorded by a PowerLab system. Statistical evaluation was done by one-way analysis of variance followed by Fisher's least significant difference test and P < 0.05 was considered statistically significant. Results: The amounts of QT (P = 0.0009) and QTc interval (P = 0.0004), RR interval (P < 0.0001), QRS duration (P = 0.004), and QRS voltage (P = 0.003) in the exercise group were significantly higher than those of the control group. However, there were no significant differences in PR interval in comparison with the control group. Exercise (P < 0.0001) and OLE (400 mg/kg, P = 0.043) alone and both in combination (P = 0.007) reduced heart rate and increased the amount of QRS voltage (P = 0.003, P = 0.047, and P = 0.046, respectively) and RR interval (P < 0.0001, P = 0.046, and P = 0.0009, respectively). Conclusion: Results of this study indicated that administration of OLE alone and in combination with exercise has negative chronotropic and positive inotropic effects and also it can prevent of prolongation of QT and QTc interval induced by severe exercise

Pomegranate seed hydroalcoholic extract improves memory deficits in ovariectomized rats with permanent cerebral hypoperfusion /ischemia

Objective: Estrogen deficit following menopause results in cognitive behaviors impairment. Severity of these impairments in menopause women suffer with cerebral hypo perfusion/ischemia (HI) cause the brain damage and neuronal death. This study aimed to evaluate the effects of pomegranate seed extract (PGSE) on avoidance memories after permanent bilateral common carotid arteries occlusion (2CCAO) in ovariectomized (OVX) rats. Materials and Methods: Adult female Wistar rats were divided randomly into eight groups with 8 rats in each group: 1) Sham-operated for ovaries and 2CCAO (ShO); 2) OVX and sham operated for ischemia (OShI); 3-7) OVX with 2CCAO (OI) received PGSE (100, 200, 400 and 800 mg/2ml/kg or normal saline, orally) for 14 days (OI+E100, 200, 400, 800 or OI+Veh); 8) OShI received most effective dose of PGSE (200 and 400 mg/kg for passive and active avoidance memories respectively). Active and passive avoidance tasks were measured in Y-maze and two-way shuttle box respectively. Data were analyzed with one-way and RM-ANOVA followed by HSD post-hoc test. Results: Sensorimotor impaired in OShI+Veh and OI+Veh (

Brain-derived neurotrophic and immunologic factors: beneficial effects of riboflavin on motor disability in murine model of multiple sclerosis

Objective(s): In the present study, C57BL/6 female mice (n=56) were used to explore the neuroprotective effects of riboflavin in motor disability of experimental autoimmune encephalomyelitis (EAE) as a model of multiple sclerosis. Materials and Methods: The animals were assigned into 7 groups: sham-operated 1 (SO1), healthy mice receiving PBS (phosphate buffer saline); sham-operated 2 (SO2), healthy mice receiving PBS and riboflavin; sham treatment 1 (ST1), EAE mice receiving water; sham treatment 2 (ST2), EAE mice receiving sodium acetate buffer; treatment 1 (T1), EAE mice receiving interferon beta-1a (INFβ-1a); treatment 2 (T2), EAE mice receiving riboflavin; treatment 3 (T3), EAE mice receiving INFβ-1a and riboflavin. After EAE induction, scoring was performed based on clinical signs. Upon detecting score 0.5, riboflavin at 10 mg/kg of body weight and/or INFβ-1a at 150 IU/g of body weight administration was started for two weeks. The brain and spinal cord levels of brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), and interleukin-17A (IL-17A) were studied using real-time PCR and ELISA methods. Results: BDNF expression and protein levels were increased in the brain and spinal cord of the T3 group compared with the other groups (