Naringenin mitigates reserpine-induced anxiety-like behavior, neurodegeneration, and oxidative stress in male rats.

Reserpine (Res) induces anxiety-like behaviors, orofacial dyskinesia, and neurodegeneration in animals, the pathophysiology of which has been related to oxidative stress. The purpose of this study was to investigate whether naringenin (NG) could prevent reserpine-induced anxiety-like behaviors, orofacial dyskinesia, and neurodegeneration in male rats. Twenty-eight male rats were distributed into different groups as follows: Control rats; vehicle rats, which received the vehicles (normal saline, orally; acetic acid, intraperitoneally); Res rats (1 mg/kg/day) every other day for 3 days; and Res + NG rats, which received NG (50 mg/kg, orally, pre-treatment for 7 days), followed by Res. Administration of Res significantly increased chewing frequency compared with the control group (P < 0.01) and NG reversed the effect of Res on this factor (P < 0.05). Res induced an anxiety-like behavior in rats in the plus maze, and pre-treatment with NG improved this behavior. In addition, Res significantly increased the level of oxidative stress markers and degenerated neurons in the striatum; NG was able to ameliorate these damages. The results of this study demonstrated that Res caused behavioral disorders and increased the levels of oxidative stress in male rats; the use of NG was effective in treating these disorders. Therefore, NG should be considered as a preventive agent for reserpine-induced brain damage in male rats.

Promising Effects of Naringenin and Melatonin against Hepatic Encephalopathy Impairments Induced by Bile Duct Ligation in Male Rats.

BACKGROUND: Bile duct ligation (BDL) is used for evaluating the protective effects of different agents with anti-inflammatory and antioxidant properties against the liver and brain damages. Naringenin (N) and melatonin (M) are used as protectants in various models of diseases. AIMS: In the current research, the combinational effects of these well-known anti-inflammatory and antioxidants agents were investigated against cerebral injuries induced by BDL in male rats. METHODS: The animals were distributed into the following groups: Sham, BDL + Vehicle and BDL+ N + M. Neuronal damages were evaluated using biochemical, motor behavioral tasks and morphological assessments. RESULTS: Based on the data, BDL resulted in decreasing locomotor activity, which was reversed by N and M. Morphological study confirmed that BDL led to neurodegeneration in the cortex of the rats, and the N and M treatment preserved cortical neurons. In addition, immunohistochemical (IHC) study of the rat cortex showed that BDL resulted in increasing the activated astrocytes, and the N and M treatment reduced the number of activated cells. CONCLUSION: These results obviously depicted combinational therapy with N and M to exert positive effects in the BDL rats, probably due to their synergistic anti-inflammatory and antioxidant activities.

Functional Antagonism of Sphingosine-1-Phosphate Receptor 1 Prevents Harmaline-Induced Ultrastructural Alterations and Caspase-3 Mediated Apoptosis.

BACKGROUND: There is a meaningful necessity for a targeted therapy of essential tremor (ET), as medications have not been developed specifically for ET. For nearly a century, many drugs have been applied in the treatment of tremor but the drug treatment of ET remains still unknown. Some potential therapeutic factors such fingolimod (FTY720) can be effectively used to treat ET in animals. In the present research, the effect of FTY720, the immunomodulatory sphingosine 1-phosphate (S1P) analog, on degeneration of cerebellar and olivary neurons induced by harmaline in male rats was investigated. METHODS: The animals were allotted into control dimethyl sulfoxide (DMSO), saline + harmaline [30 mg/kg, intraperitoneally, (i.p.)], harmaline + FTY720 (1 mg/kg, i.p, 1 h and 24 h before harmaline injection) groups (n = 10). The cerebellum and inferior olive nucleus (ION) were studied for neuronal degeneration using immunohistochemistry (IHC) and ultrastructural study by transmission electron microscopy (TEM) techniques. RESULTS: Harmaline caused neuronal cell loss, caspase-3 mediated apoptosis, astrocytosis and ultrastructural changes in cerebellar Purkinje cells and inferior olive neurons. FTY720 exhibited neuroprotective effects on cerebellar Purkinje cells and inferior olivary neurons. CONCLUSION: These results suggest that FTY720 has potential efficacy for prevention of ET neurodegeneration and astrocytosis induced by harmaline in male rats.

Nepeta Dschuparensis Bornm Extract Moderates COX-2 and IL-1ß Proteins in a Rat Model of Cerebral Ischemia.

BACKGROUND: Nepeta dschuparensis Bornm (NP) is used as a medicinal herb in Iran. In traditional medicine, this herb is extensively employed for curing ailments such as cardiovascular diseases. NP has antioxidant and anti-inflammatory properties. This project examined the effects of the NP extract on cyclooxygenase-2 (COX-2) and interleukin-1ß (IL-1ß) protein levels and its efficacy in neuroprotection in a cerebral ischemia-reperfusion model. METHODS: Twenty-six male rats were randomly divided into 3 groups: 1) sham (n=6): no middle cerebral artery occlusion (MCAO) procedure, 2) control (n=10): MCAO procedure and treatment with normal saline, and 3) NP extract (n=10): MCAO procedure and treatment with the NP extract (20 mg/kg, i.p.) at the beginning of reperfusion. To examine the injury caused by cerebral ischemia, we measured motor coordination and the infarct area using the rotarod test and triphenyl tetrazolium chloride staining, respectively. IL-1ß and COX-2 protein levels, as inflammatory markers, were measured by immunoblotting assay. The statistical analyses were performed using SPSS, version 16, and the data are expressed as means±SEMs. Statistical difference was evaluated using the one-way ANOVA, followed by the post hoc LSD test (P<0.01). RESULTS: Treatment with the NP extract significantly diminished the infarct volume and alleviated the motor coordination disorder induced by cerebral ischemia. The NP extract administration significantly attenuated the increase in IL-1ß and COX-2 protein levels too (P<0.01). CONCLUSION: The beneficial effects of the NP extract are related to its ability to decrease the levels of IL-1ß and COX-2.

Date seed extract ameliorates ß-amyloid-induced impairments in hippocampus of male rats.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder among the elderly. Because the existing treatments for Alzheimer's disease only offer limited symptomatic alleviation, more efficient therapeutic agents are urgently needed. Date seed is a hepatoprotective and neuroprotective agent. Date seed extract (DSE) has bioactive components like phenolics, flavonoids, and vitamins. In view of the ameliorative effects of DSE against an oxidative injury, the current study was designed to reveal whether DSE has a neuroprotective resource in the rat model of Alzheimer's disease. In the current study, 24 adult male Sprague-Dawely rats were divided into three groups (n=8) of: Sham (Distilled Water, 3µl intracerebroventricular (ICV) injection), ß-Amyloid (ß-amyloid, 3µl ICV injection), and DSE-treated groups (80mg/kg, Intraperitoneal (IP) injection), for 12days. Twelve days after Alzheimer induction, behavioral analysis, the Morris Water Maze (MWM), as well as western blot and histological studies were performed to reveal the neuroprotective potential of DSE in rats. Administration of DSE significantly restored memory and learning impairments induced by Aß in the MWM test. DSE significantly decreased the caspase-3 expression level in the treated group. In addition, DSE reduced the number of degenerated neurons in the hippocampal CA1 subfield of the DSE treated rats. These results demonstrate that DSE may have beneficial effects in the prevention of Aß-induced Alzheimer in a rat model. Date seed extract may have advantageous effects in preventing Alzheimer's disease in male rats.

Apelin-13 protects rat primary cortical glia-neuron co-culture against pentylenetetrazole-induced toxicity.

In spite of recent advances in the treatment of epilepsy, up to 35% of people living with the condition do not respond to accessible anti-epileptic drugs (AEDs) and continue to experience regular, devastating and potentially life-threatening seizures. Neuronal death is a significant feature of epilepsy in humans and experimental models. It has been reported that apelin, an endogenous ligand for the angiotensin-1-like receptor (APJ), has anticonvulsive as well as protective effects in some neurodegenerative situations. In the current study, we investigated the effects of apelin-13 on pentylenetetrazole (PTZ)-induced neurotoxicity in rat's brain primary culture. Cell injury was induced by 20mM PTZ and the cells viability was examined by MTT assay. Intracellular calcium, reactive oxygen species (ROS) and mitochondrial membrane potential were determined by fluorescence spectrophotometry methods. Markers of apoptosis were determined by immunohistochemistry. The data showed that PTZ caused a loss of cell viability and mitochondrial membrane potential. In addition, intracellular reactive oxygen species, intracellular calcium, COX-2 and caspase-3 positive cells were increased in PTZ-treated cells. Incubation of the cells with aplein-13 (10µM) elicited protective effect and reduced markers of cell damage and death. The results suggest that apelin-13 has protective effects against PTZ-induced toxicity and such effects are accompanied by its calcium blocking, antioxidant and, anti-inflammatory and anti-apoptotic properties.

Anticonvulsant and neuroprotective effects of apelin-13 on pentylenetetrazole-induced seizures in male rats.

Epilepsy is a common neurological disorder with no effective treatment or cure. Neuropeptide apelin is an endogenous ligand of angiotensin receptor-like 1 (APJ). It has been shown that apelin has protective and anti-neurodegenerative properties. This study was designed to evaluate the effect of apelin-13 on pentylenetetrazole (PTZ)-induced rat model of seizure. Adult male Wistar rats were divided into the experimental groups as follows: control group receiving PTZ; apelin-treated group which received apelin-13 before PTZ; apelin+F13A-treated group which received apelin-13 plus the apelin receptor antagonist (F13A) before PTZ; apelin+naloxone group which received apelin-13+naloxone before PTZ. Behavioral scoring was used to access seizure. The expression level of APJ was measured by western blotting. Neuronal degeneration, apoptosis and astrocyte activation were evaluated by vanadium acid fuchsin (VAF) staining and immunohistochemistry. Our data demonstrated that apelin-13 pretreatment significantly inhibited seizure threshold (p<0.001) and tonic-clonic latency (p<0.001) compared with the control group. In addition, PTZ-induced up-regulation of APJ was attenuated by apelin-13 treatment. Histological and immunohistochemical findings also showed that apelin-13 could protect cortical neurons against PTZ-induced neuroinflammation and apoptosis. In conclusion, apelin-13 has anticonvulsive and neuroprotective properties against PTZ-induced seizure in rats and provided a new pharmacological aspect of the neuropeptide apelin.

The anticonvulsant and neuroprotective effects of walnuts on the neurons of rat brain cortex.

BACKGROUND: Epilepsy is a chief communal health problem. Antiepileptic drugs only provide symptomatic treatment. Walnut Kernels (WK) have high concentrations of phenolic compounds, which have beneficial effects on human health because of their antioxidant and anti-atherogenic properties. The present study was designed to evaluate the efficacy of WK supplementation for the prevention of experimental epilepsy in male rats. METHODS: WISTAR ADULT MALE RATS WERE DIVIDED INTO THREE GROUPS: a control group (PTZ injection, fed with ordinary food), experimental group (PTZ injection, fed with WK) and a sham group (no PTZ injection, only for histological studies). Pentylenetetrazole (PTZ) was administered after the prescribed time. RESULTS: WKs displayed anti-epileptogenic properties, and WK supplementation was associated with increased seizure threshold and reduced mortality in the experimental group versus controls. CONCLUSION: Use of WK may be helpful in prevention of PTZ-induced seizure and its further neurodegeneration in male rats.