Anandamide improves food intake and orexinergic neuronal activity in the chronic sleep deprivation induction model in rats by modulating the expression of the CB1 receptor in the lateral hypothalamus.

Sleep deprivation alters orexinergic neuronal activity in the lateral hypothalamus (LH), which is the main regulator of sleep-wake, arousal, appetite, and energy regulation processes. Cannabinoid receptor (CBR) expression in this area is involved in modulating the function of orexin neurons. In this study, we investigated the effects of endocannabinoid anandamide (AEA) administration on improving food intake and appetite by modulating the activity of orexin neurons and CB1R expression after chronic sleep deprivation. Adult male Wistar rats (200-250 g) were randomly divided into three groups: control + vehicle (Control), chronic sleep deprivation + vehicle (SD), and chronic sleep deprivation +20 mg/kg AEA (SD + A). For SD induction, the rats were kept in a sleep deprivation device for 18 h (7 a.m. to 1 a.m.) daily for 21 days. Weight gain, food intake, the electrical power of orexin neurons, CB1R mRNA expression in hypothalamus, CB1R protein expression in the LH, TNF-α, IL-6, IL-4 levels and antioxidant activity in hypothalamus were measured after SD induction. Our results showed that AEA administration significantly improved food intake (p < 0.01), Electrical activity of orexin neurons (p < 0.05), CB1R expression in the hypothalamus (p < 0.05), and IL-4 levels (p < 0.05). AEA also reduced mRNA expression of OX1R and OX2R (p < 0.01 and p < 0.05 respectively), also IL-6 and TNF-α (p < 0.01) and MDA level (p < 0.05) in hypothalamic tissue. As a consequence, AEA modulates orexinergic system function and improves food intake by regulating the expression of the CB1 receptor in the LH in sleep deprived rats.

Neuroprotective effect of anethole against rotenone induced non-motor deficits and oxidative stress in rat model of Parkinson's disease.

INTRODUCTION: Non-motor symptoms (NMS) have high prevalence in patients with Parkinson's disease (PD). These symptoms are mainly the result of increased oxidative stress and neuronal damage. In this study we investigated the possible neuroprotective effects of anethole as a potent antioxidant on rotenone-induced behavioral deficits, hippocampal neuronal death, and oxidative stress profile in rats. METHODS: Male Wistar rats were administered with anethole (62.5, 125, and 250 mg/kg, i.g) concomitantly with rotenone (2 mg/kg, s.c) for 35 days. Shuttle box and novel object recognition tests were performed to determine cognitive functions, and tail flick test was used to measure pain sensitivity. The levels of BDNF, MDA, SOD, and GPx were assayed in the hippocampus. Hippocampal neuronal damage was evaluated using cresyl violet staining technique. RESULTS: Chronic administration of rotenone induced cognitive deficit and reduced thermal pain threshold. Rotenone also decreased SOD and GPx activities, increased MDA level, and reduced the expression of BDNF in the hippocampus. In addition, hippocampal neuronal loss was increased in rotenone treated rats. Treatment with high dose of anethole (250 mg/kg) improved cognitive function and increased pain threshold in all three doses (62.5, 125, and 250 mg/kg). Despite the unchanged SOD and GPx activities, hippocampal levels of MDA was significantly decreased after high-dose anethole treatment. Moreover, High dose of anethole increased the number of surviving neurons in the hippocampus, but couldn't increase the BDNF expression. CONCLUSION: Our findings indicated that anethole has antioxidant and neuroprotective effects against non-motor disorders induced by rotenone toxicity.

Protective Effects of Co-administration of Zinc and Selenium Against Streptozotocin-Induced Alzheimer's Disease: Behavioral, Mitochondrial Oxidative Stress, and GPR39 Expression Alterations in Rats.

Changes in the concentrations of trace metals such as zinc (Zn) and selenium (Se) can pathologically lead to neurodegenerative conditions such as the Alzheimer's disease (AD). Previous studies have shown that mitochondrial dysfunction plays an important role in the pathogenesis of AD. Several male Wistar rats were randomly divided into five groups: sham group, AD group that received 3 mg/kg of streptozotocin (STZ) intracerebroventricularly, AD + Zn group that received 10 mg/kg of Zn intraperitoneally (i.p.) for 1 week, AD + Se group that received 0.1 mg/kg of Se i.p. for 1 week, and AD + Zn + Se group that received 10 mg/kg of Zn i.p. plus 0.1 mg/kg of Se i.p. for 1 week. At end of the study, behavioral tests and mitochondrial oxidative stress and GPR39 gene expression evaluations were carried out. Co-administration of Zn and Se significantly decreased the potential collapse of mitochondrial membrane, reactive oxygen species levels, and lipid peroxidation levels while significantly increased cognitive performance, superoxide dismutase (SOD), glutathione peroxidase, and catalase activity in the brain mitochondria compared with the STZ group. In addition, no significant changes were observed in GPR39 expression in the co-treated group. Findings of the current study showed that ZnR/GPR39 receptor, mitochondrial dysfunction, and oxidative stress play important roles in the pathogenesis of AD. Co-treatment of Zn and Se improved the cognitive performance, mitochondrial dysfunction, and oxidative stress caused by STZ-induced AD. Therefore, therapeutic approaches to improve mitochondrial function could be effective in preventing the initiation and progression of AD.

Update on riboflavin and multiple sclerosis: a systematic review.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Riboflavin plays an important role in myelin formation, and its deficiency is implicated as a risk factor for multiple sclerosis. Here, we systematically reviewed the literature concerning the health benefits of riboflavin on MS. The literature recorded within four main databases, including relevant clinical trials, experimental, and case-control studies from 1976 to 2017 were considered. Both human and animal studies were included for review, with no restrictions on age, gender, or ethnicity. Experimental studies demonstrated that riboflavin deficiency triggers neurologic abnormalities related to peripheral neuropathies such as demyelinating neuropathy. Moreover, randomized controlled trials (RCT) and case-control studies in which MS patients received riboflavin supplementation or had higher dietary riboflavin intake showed improvements in neurological motor disability. Riboflavin is a cofactor of xanthine oxidase and its deficiency exacerbates low uric acid caused by high copper levels, leading to myelin degeneration. The vitamin additionally plays a significant role in the normal functioning of glutathione reductase (GR) as an antioxidant enzyme, and conditions of riboflavin deficiency lead to oxidative damage. Riboflavin promotes the gene and protein levels of brain-derived neurotrophic factor (BDNF) in the CNS of an animal model of MS, suggesting that BDNF mediates the beneficial effect of riboflavin on neurological motor disability. Research to date generally supports the role of riboflavin in MS outcomes. However, further observational and interventional studies on human populations are warranted to validate the effects of riboflavin.

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.

Agmatine protects against intracerebroventricular streptozotocin-induced water maze memory deficit, hippocampal apoptosis and Akt/GSK3ß signaling disruption.

Centrally administered streptozotocin (STZ), is known to cause Alzheimer׳s like memory deterioration. It mainly affects insulin signaling pathways such as PI3/Akt and GSK-3ß which are involved in cell survival. Previous studies indicate that STZ increases the ratio of Bax/Bcl-2 and thereby induces caspase-3 activation and apoptosis. Agmatine, a polyamine derived from l-arginine decarboxylation, is recently shown to exert some neuroprotective effects. This study aimed to assess if agmatine reverses STZ-induced memory deficits, hippocampal Akt/GSK-3ß signaling disruption and caspase-3 activation. Adult male Sprague-Dawely rats weighing 200-250 g were used. The canules were implanted bilaterally into lateral ventricles. STZ was administered on days 1 and 3 (3 mg/kg) and agmatine treatment (40 or 80 mg/kg) was started from day 4 and continued in an every other day manner till day 14. The animal׳s learning and memory capability was assessed on days 15-18 using Morris water maze. After complement of behavioral studies the hippocampi was isolated and the amounts of hippocampal cleaved caspase-3 (the landmark of apoptosis), Bax/Bcl-2 ratio, total and phosphorylated forms of GSK-3ß and Akt were analyzed by western blot. The results showed that agmatine in 80 but not 40 mg/kg reversed the memory deterioration induced by STZ. Western blot analysis revealed that STZ prompted elevation of caspase-3; Bax/Bcl-2 ratio and disrupted Akt/GSK-3ß signaling in the hippocampus. Agmatine treatment prevented apoptosis and Akt/GSK-3ß signaling impairment induced by STZ. This study disclosed that agmatine treatment averts not only STZ-induced memory deterioration but also hippocampal apoptosis and Akt/GSK-3ß signaling disruption.

Motor and cognitive deficits due to permanent cerebral hypoperfusion/ischemia improve by pomegranate seed extract in rats.

This study aimed to evaluate the effect of two weeks oral administration of Pomegranate Seed Extract (PGSE) on active avoidance memory and motor coordination activities after permanent bilateral common carotid arteries occlusion (2CCAO) in male adult rats. Adult male albino rats of Wistar strain (250 ± 20 g, 3-4 months) were used. Animals were divided into eight groups with 10 in each: (1) Sham operated (Sh); (2) Ischemic (I); (3) Ischemic received 100 mg kg(-1) PGSE, orally (I+E100); (4) Ischemic received 200 mg kg(-1) PGSE, orally (I+E200); (5) Ischemic received 400 mg kg(-1) PGSE, orally (I+E400); (6) Ischemic received 800 mg kg(-1) PGSE, orally (I+ E800); (7) Ischemic received 2 mL kg(-1) normal saline, orally (I+Veh); (8) Sham operated received 400 mg kg(-1) PGSE, orally (Sh+E400). In order to make 2CCAO an animal Cerebral Hypoperfusion Ischemia (CHI) model, carotid arteries were ligatured and then bilaterally cut. To evaluate active avoidance task, Correct Response Percentages (CRP) was measured by Y-maze apparatus and motor coordination activity was evaluated using standard behavioral tests by rotarod apparatus in all the rats. It was found that memory. Memory and motor coordination activities were significantly impaired in the rats after CHI (p < 0.01). PGSE treatment significantly improved impairment of memory and motor coordination in the rats with 2CCAO (p < 0.001). PGSE exhibited therapeutic potential for memory and muscular coordination, which was most likely related at least in some part to its antioxidative and free radical scavenging actions.

Neuroprotective effects of oral gallic acid against oxidative stress induced by 6-hydroxydopamine in rats.

Free radical-induced neural damage is implicated in neurodegenerative diseases and antioxidants have protective activity. In the present study, we examined the effect of gallic acid (GA; 50, 100 and 200mg/kg, p.o. for 10 days) on memory deficit and cerebral oxidative stress induced by 6-hydroxydopamine (6-OHDA; 8 µg/2 µL) injected into the medial forebrain bundle (MFB, full nigral lesion) as an animal model of Parkinson's disease (PD). The results showed that 6-OHDA significantly reduced the passive avoidance memory performance, non-enzymatic (total thiol) and enzymatic [glutathione peroxidase (GPx)] antioxidant contents and increased the level of malondialdehyde (MDA) in the hippocampus and striatum of vehicle-treated group as compared to sham-operated rats. Furthermore, oral administration of GA significantly increased the passive avoidance memory, total thiol and GPx contents and also decreased MDA levels in the above tissues. The results suggest that GA has neuroprotective activity against 6-OHDA-induced oxidative stress via enhancement of cerebral antioxidant defence.

Effect of grape seed extract on lead induced hypertension and heart rate in rat.

The main objective of this study was to evaluate the potential protective effect of red Grape Seed Extract (GSE) on lead induced hypertension (HTN) and Heart Rate (HR) in male Wistar rats. The rats were randomly assigned to one of 4 groups: Each group received lead acetate (100 ppm in drinking water), GSE (100 mg kg(-1), orally) or Lead + GSE for 45 days. Another group assigned as control group provided with tap water and regular pellet food. The Systolic Blood Pressure (SBP) and heart rate were determined by tail plethysmography coupled to a computer system. There was a sustained elevation of SBP in lead exposed rats that significantly increased at day 18 (lead treated, 112.7 +/- 2.7 mmHg, vs. control, 105.6 +/- 2.6 mmHg, n = 10, p < 0.05) and reached a maximum level at day 36 (lead treated, 124.9 +/- 2.3 mmHg, vs. control, 103.6 +/- 3.1 mmHg, n = 10, p < 0.001). However, the other three groups; showed no significant changes in SBP. Furthermore, the heart rate was increased sustainly in lead exposed animals that was statistically significant at days 36 and 45 (lead treated group, 404.5 +/- 9.4 vs. control group, 381.7 +/- 6.7, n = 10, p < 0.05). The blood lead level in both lead and lead + GSE treated groups was increased significantly compared with control and GSE treated groups (p < 0.001). However, GSE administration had no effect on the blood lead level in lead treated group. According to the result of this study, it may be concluded that GSE could have beneficial effect in protecting the cardiovascular system through its antioxidant activity against oxidative stress.