Effects of Nostoc commune extract on the cerebral oxidative and neuroinflammatory status in a mice model of schizophrenia.

Cyanobacterium Nostoc commune has long been used to alleviate various diseases. This research examines the effects of Nostoc commune extract (NCE) against behavioral disorders, cerebral oxidative stress, and inflammatory damage in the ketamine-induced schizophrenia model. Oral NCE administration (70 and 150 mg/kg/d) is performed after intraperitoneal ketamine injection (20 mg/kg) for 14 consecutive days. The forced swimming and open field tests are used to assess schizophrenia-like behaviors. After the behavioral test, dopamine (DA) level, oxidative stress markers, as well as the interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) expression are measured in the cerebral cortex. The results show that NCE treatment ameliorates KET-induced anxiety and depressive-like behaviors in OFT and FST, respectively. NCE considerably decreases the malondialdehyde (MDA) and DA levels and IL-6 and TNF-α expressions in mice with schizophrenia-like symptoms. Also, a significant increase is observed in the glutathione (GSH) level and catalase (CAT), superoxide dismutase (SOD), and glutathione reductase (GRx) activity in cerebral tissue. The present study shows that NCE treatment effectively improves KET-induced schizophrenia-like behaviors and oxidative and inflammatory damage. Therefore, NCE, via its bioactive constituents, could have strong neuroprotective effects in the schizophrenia-like model.

Neuroprotective effects of alpha-pinene against behavioral deficits in ketamine-induced mice model of schizophrenia: Focusing on oxidative stress status.

Schizophrenia (SCZ) is a profound neurological disorder that affects approximately 1% of the global population. Alpha-pinene (α-pinene) is a natural and active monoterpene found in coniferous tree oil, primarily pine, with diverse pharmacological characteristics, including antioxidative, anxiolytic, and antidepressant properties. This research study delves into the neuroprotective effects of α-pinene on oxidative stress, memory deficits, and depressive and anxiety-like behaviors in a ketamine-induced mice model of SCZ using male mice. The mice were randomly divided into six groups: vehicle, control, positive control, ketamine, α-pinene at 50 mg/kg, and α-pinene at 100 mg/kg. Treatment of the ketamine-induced mice model of SCZ with α-pinene yielded significant improvements in depressive and anxiety-like behaviors and cognitive impairments. Furthermore, it significantly elevated glutathione (GSH) levels, total antioxidant capacity (TAC), dopamine levels, catalase (CAT), and superoxide dismutase (SOD) activities while markedly reducing malondialdehyde (MDA) levels. The current study establishes that α-pinene treatment effectively mitigates oxidative damage, cognitive deficits, and depressive and anxiogenic-like behaviors in the brains of ketamine-treated mice. Therefore, α-pinene treatment is an efficacious approach to forestall the neurobehavioral and neurobiochemical adverse effects of the ketamine-induced SCZ model of mice.

Nano-hesperetin ameliorates 6-hydroxydopamine-induced behavioral deficits and oxidative damage by up-regulating gene expression of antioxidant enzymes.

Objective: Hesperetin (Hst) has shown several pharmacological effects. The efficacy of Hst is highly restricted in vivo due mainly to poor bioavailability. This investigation was intended to compare the influence of Hst and nano-Hst treatment on 6-hydroxydopamine (6-OHDA)-induced behavioral deficits and oxidative stress in rats. Materials and Methods: Forty-two Wistar male rats were equally assigned to 6 groups: control, 6-OHDA, Hst5, Hst10, nano-Hst5, and nano-Hst10. Treatment with Hst and nano-Hst was initiated 1 day after the intrastriatal injection of 6-OHDA and continued for 28 days. Behavioral deficits were evaluated using apomorphine-induced rotation test (AIRT), narrow beam test (NBT) and novel object recognition test (NORT), and the hippocampus and striatum were used to evaluate oxidative stress-related parameters. Results: The rats injected only with 6-OHDA showed learning and memory deficits but Hst and nano-Hst treatments improved it (p<0.001). Compared to the control group, a marked promotion in Malondialdehyde (MDA) levels along with a marked reduction in activities and gene expression of antioxidant enzymes and reduced glutathione (GSH) levels in the hippocampus and striatum were observed in the 6-OHDA group (p<0.01). However, administration of Hst and nano-Hst remarkably diminished MDA levels (p<0.01), and significantly increased the activities (p<0.01) and gene expression of antioxidant enzymes (p<0.05) and GSH levels (p<0.01) compared to the 6-OHDA group. In most parameters, nano-Hst has shown better therapeutic effects than Hst. Conclusion: Our findings reveal that Hst can be considered as a potential candidate for the treatment of neurodegenerative diseases and that nano-Hst may have better bioavailability.

Anxiolytic-like effects of citral in the mouse elevated plus maze: involvement of GABAergic and serotonergic transmissions.

Citral, a monoterpene which is a part of the essential oil of several medicinal plants, is generally regarded as safe for human and animal consumption. Studies have introduced citral as a functional component of some essential oils in anxiolytic and antidepressant therapies; however, the neuropharmacological characteristics of citral have not yet been reported. In the present study, we evaluated the anxiolytic activities of citral in comparison to two standard anxiolytics, diazepam and buspirone, in Swiss albino mice by intraperitoneal administration of 1, 2, 5, 10, and 20 mg/kg using elevated plus maze (EPM) and open-field test (OFT). Moreover, we also examined whether the GABAA-benzodiazepine and 5-HT1A receptor are involved in the anxiolytic-like effects of citral by pretreatment with flumazenil and WAY-100635, respectively. Citral dose-dependently decreased the number of border crossings and time spent in borders, and also the number of grooming and rearing in OFT without altering the exploratory behavior of mice. In the EPM, this monoterpene led to a significant increase in number of entries in open arms and time spent in open arms, as well as a decrease in time spent in closed arms. Pretreatment with flumazenil and WAY-100635 both could reverse the anxiolytic effects of the citral in the EPM. These results suggest that anxiolytic activity of citral occurs via the GABAA and 5-HT1A receptor modulation.

Sumac and gallic acid-loaded nanophytosomes ameliorate hippocampal oxidative stress via regulation of Nrf2/Keap1 pathway in autistic rats.

Autism spectrum disorders cover a range of neurodevelopmental disorders characterized by impairments in social interaction and cognitive deficits. Phenolic compound applications have been restricted due to their poor solubility, bioavailability, and low stability. This paper aimed to explore the neuroprotective effects of sumac and gallic acid-loaded nanophytosomes (GNP) on oxidative stress-induced cognitive impairment and Nrf2/Keap1 gene expression in the autism model. Valproic acid (VPA) was administered intraperitoneally at doses of 500 mg/kg to female rats during gestational 12.5 days (E12.5). The prenatal VPA-exposed rats were divided into five groups, including VPA, VPA treated with sumac, gallic acid (GA), sumac-loaded nanophytosome (SNP), and GNP at doses of 20 mg/kg for 4 weeks (n = 6). A novel object test was conducted and antioxidant parameters and Nrf2/Keap1gene expression were evaluated in the hippocampus. According to the obtained results, the rat model of autism exhibited recognition memory impairment. We observed an increase in glutathione peroxidase (GPx), glutathione reductase (GRx), superoxide dismutase (SOD), catalase (CAT) enzyme activity, total antioxidant capacity (TAC), and glutathione (GSH) levels. Furthermore, sumac and GNP improved recognition memory deficits and increased GPx, GRx, SOD, and CAT activities, GSH and TAC levels, and Nrf2/Keap1gene expression in the hippocampal area. Our results also suggested that SNP and GNP ameliorate VPA-induced learning and memory deficits more efficiently than sumac extract and pure GA by reducing oxidative stress, enhancing antioxidant enzyme activity, and Keap1/Nrf2 gene expression. The present study demonstrated that the utilization of SNP and GNP significantly improved recognition memory deficits.

Anti-apoptotic effect of silymarin-loaded chitosan nanoparticles on hippocampal caspase-3 and Bcl-2 expression following cerebral ischemia/reperfusion injury.

BACKGROUND: Cerebral ischemia/reperfusion (I/R) causes memory and learning impairments and apoptosis in the hippocampus. The aim of present study aimed to investigate the anti-apoptotic effects of silymarin-loaded chitosan nanoparticles (SM-CS-NPs) on the expression of Bcl-2 and Caspase-3 genes in hippocampal neurons after I/R injury. MATERIAL AND METHODS: SM and SM-CS-NPs were orally administered (15 mg/kg) for 14 days, and then cerebral I/R injury was induced by the bilateral common carotid artery occlusion (BCCAO). One day after I/R induction, memory and learning impairments and various biochemical estimations were assessed. RESULTS: Our results indicated that SM-CS-NPs improved I/R-induced memory and learning impairments and oxidative damage in the hippocampal region. The qRT-PCR analysis indicated that SM-CS-NPs pretreatment inhibited I/R-induced neuronal apoptosis by increasing the expression of Bcl-2 and decreasing the expression of Caspase-3 in the hippocampus. CONCLUSION: These findings suggest that SM-CS-NPs exert neuroprotective effects, and the neuroprotection is likely to be associated with the regulation of Bcl-2 and Caspase-3, leading to inhibition of apoptotic cell death in hippocampal neurons.

Evaluation of hesperetin-loaded on multiple wall carbon nanotubes on cerebral ischemia/reperfusion injury in rats.

The present study aimed to develop novel hesperetin-loaded on multiple wall carbon nanotubes (Hst-MWCNTs) to resolve the restricted bioavailability of hesperetin (Hst) and to enhance its preventive effect on cerebral ischemia-reperfusion (I/R). The physicochemical characteristics of Hst-MWCNTs were evaluated by Fourier-transform infrared spectra (FT-IR) and field emission scanning electron microscopy (FE-SEM). Forty male Wistar rats were randomly divided into five groups (control, I/R, MWCNTs, Hst, and Hst-MWCNTs). Hst, MWCNTs and Hst-MWCNTs (15 mg/kg orally) were pretreated for 14 days, and then I/R was induced by bilateral common carotid artery occlusion (BCCAO). Learning and memory deficits were evaluated using the novel object recognition test (NORT). The percentage of infarct size, catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GRx), glutathione peroxidase (GPx) activities, malondialdehyde (MDA), and glutathione (GSH) levels was evaluated. Caspase-3 and Bcl-2 expressions were detected by qRT-PCR and Western blot analysis. Compared to the I/R group, Hst-MWCNTs considerably reduced learning and memory deficits, infarct size, and MDA levels. CAT, SOD, GRx, GPx activities and GSH levels were significantly increased in the Hst-MWCNTs group than in the I/R group. Additionally, Hst-MWCNTs significantly reduced the Caspase-3 expression but increased the Bcl-2 expression. All these results indicated that MWCNTs could be used as a promising novel carrier to enhance the oral bioavailability of Hst and to treat cerebral I/R injury.

Hesperetin nanoparticles attenuate anxiogenic-like behavior and cerebral oxidative stress through the upregulation of antioxidant enzyme expression in experimental dementia of Alzheimer's type.

Background: In this study, we investigate the neuroprotective effects of Hesperetin (Hst) and Nano-Hst on anxiogenic-like behavior and cerebral antioxidant defenses at transcriptional and enzymatic levels in a streptozotocin (STZ)-induced Alzheimer rat model.Methods: Wistar rats were administrated with Hst and Nano-Hst (10 and 20 mg/kg/d) for three weeks. The elevated plus-maze test assessed anxiogenic-like behavior. After behavioral test, activity and gene expression of catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GRx) enzymes, as well as malondialdehyde (MDA) and glutathione (GSH) levels, were measured in the cerebral cortex.Results: Based on our results, a rat model of Alzheimer's disease (AD) exhibited anxiogenic-like behavior, activity and gene expression of cerebral antioxidant enzymes and GSH level was decreased while the MDA level was increased. Hst and Nano-Hst treatment reversed anxiogenic-like behavior, and the activities of antioxidant enzymes were elevated. Hst and Nano-Hst effects on the gene expression of CAT, SOD and GRx were confirmed by quantitative real-time PCR (qRT-PCR) in which the expression levels of these genes in the cerebral brain were significantly increased compared to STZ group.Conclusions: These findings indicated that the administration of Hst and Nano-Hst may be used to treat anxiety -related to AD via an up-regulation of cerebral antioxidant enzyme gene.

Protective Effects of Curcumin and its Nano-Phytosome on Carrageenan-Induced Inflammation in Mice Model: Behavioral and Biochemical Responses.

BACKGROUND AND PURPOSE: Natural compounds are used for prevention of inflammation. Curcumin has antioxidant and anti-inflammatory properties, and loading it into nano-phytosomes may improve its efficiency. The present study investigates the effects of curcumin and its nano-phytosome on behavioral and biochemical responses in carrageenan-induced inflammation in the mice model. METHODS: The mice were divided into six groups and received oral administration of curcumin or its nano-phytosome at a dose of 15 mg/kg for seven days before the administration of carrageenan. Acute inflammation in the mice was induced by administration of carrageenan (1%) into the subplantar region of the left paw. Antioxidant activity and behavioral responses were then evaluated. RESULTS: The results showed that the serum concentrations of antioxidant enzymes were significantly higher in the sal+sal group compared to the cara+sal group (P<0.05). Using nanophytosome, separately and in combination with indomethacin, increased the levels of antioxidant enzymes compared to the cara+sal group (P<0.05). Latency was significantly lower in the cara+sal group compared to the cara+sal group (P<0.05), but it was considerably higher in other groups, especially in the cara+nano.ph.cur+indo group (P<0.05). CONCLUSION: It can be stated that the nano-phytosome of curcumin could improve antioxidant and behavioral responses in inflamed mice.

Hesperetin and it nanocrystals ameliorate social behavior deficits and oxido-inflammatory stress in rat model of autism.

Prenatal exposure to valproic acid (VPA) induces behavioral disorders and enhancement of oxido-inflammatory stress in Autism Spectrum Disorders (ASDs). The aim of this study was to investigate the comparative effects of hesperetin (Hst) and nano-hesperetin on social behavior deficits and oxido-inflammatory indexes in prenatally valproic acid-exposed rat offspring. Pregnant Wistar rats on embryonic day 0 (E0) were segregated into six groups; Group-1 served as vehicle, received distillated water orally (PO) from E1 until the end of lactation and saline intraperitoneally (i.p) on E12.5. Group-2 received sodium valproate (500 mg/kg in 0.9% saline, i.p) on E12.5 was considered as VPA-exposed group, Group-3 to 6 were VPA-exposed which received hesperetin and nano-hesperetin (10 and 20 mg/kg/day, PO) from E0 until the end of lactation respectively. Social interaction and open field tests were conducted on postnatal day 28 (PND 28) and PND 30, cerebral antioxidant enzymes activity and biochemical indexes, the level of inflammatory factors in plasma and histopathology of cerebellum were estimated on PND 28 and PND 30. Prenatal valproic acid-exposed rat exhibited poor sociability and high level of anxiety-like behaviors (P <  0.05). In addition, increased level of oxidative stress and inflammation were found by determining different oxido-inflammatory markers. Hesperetin and nano-hesperetin treatment improved the behavioral disorder and reduced the oxidative stress in brain and significantly (p <  0.05) plasma's inflammation indexes. In conclusion, it can be state that nano-hesperetin exerts neuroprotective action in comparison with hesperetin and could be efficacious for treatment of VPA animal model of autism during pregnancy and lactation.

Hesperetin reduces myelin damage and ameliorates glial activation in lysolecithin-induced focal demyelination model of rat optic chiasm.

Visual impairment is considered as the most common initial manifestation of multiple sclerosis (MS) patients. It has been shown that hesperetin (Hst), a flavonoid of citrus fruit, possesses anti-inflammatory and antioxidant effects both in vitro and in vivo. The present study was designed to evaluate the pharmacological/medicinal effects of Hst treatment on myelin repair and glial activation in lysolecithin (LPC)-induced focal demyelination model. In order to induce local demyelination model, LPC 1% (2 µL) was injected into the optic chiasm of rats. Animals received oral administration of Hst at dose of 20 mg/kg for 14 or 21 days post lesion induction. Visual evoked potential (VEP) recordings were conducted before and also on days 7, 14 and 21 post LPC injection. Glial activation and myelination of optic chiasm were evaluated by immunostaining on brain sections. Analysis of VEPs data revealed that oral administration of Hst effectively reduced the latency of N1 waves. Immunostaining results showed the reduced number of astrocytes and microglia in animal which were treated with Hst. Furthermore, the extent of demyelination area was decreased in animals treated by Hst. Taken together; our results suggest that Hst treatment significantly protects and repairs myelin sheath, therefore it might be regarded as effective supplementary agent in demyelinating disorders, particularly MS.

Anxiolytic and antidepressant activities of Pelargonium roseum essential oil on Swiss albino mice: Possible involvement of serotonergic transmission.

The anxiolytic and antidepressant activities of the Reunion Geranium (Pelargonium roseum Willd) essential oil (EO) were evaluated in male Swiss albino mice by intraperitoneal administration of 10, 20, and 50 mg/kg bw using elevated plus maze (EPM), open-field test (OFT), and forced swimming test (FST). Moreover, we evaluated whether the 5-HT1A and GABAA -benzodiazepine receptor systems are involved in the anxiolytic effects through the coadministration of WAY-100635 (a selective 5-HT1A receptor antagonist) and flumazenil (an antagonist of benzodiazepine). GC-MS revealed the monoterpene alcohols citronellol (35.9%) and geraniol (18.5%) as the main components of the P. roseum EO. EO was effective in increasing the total number of entries and time spent in the open arms of EPM whereas number of rearing in OFT was significantly decreased in comparison with the control. In the FST, immobility time decreased in EO treated mice. Pretreatment with WAY-100635, but not Flumazenil, was able to reverse the effects of the EO in the EPM and FST, indicating that the EO activity occurs via the serotonergic but not GABAergic transmission. Overall, results of this work showed significant anxiolytic and antidepressant activity of P. roseum EO and confirmed the traditional uses of Pelargonium species as calming agents.

Neuroprotective effect of hesperetin and nano-hesperetin on recognition memory impairment and the elevated oxygen stress in rat model of Alzheimer's disease.

Alzheimer disease (AD) is a progressive dementia affecting a large proportion of the aging population. There is evidence that brain tissue in patients with AD is exposed to oxidative stress during the course of the disease. Hesperetin (Hst) is a natural flavonoid, which has been reported to exert various biological activities such as antioxidant and anti-inflammatory effect. The present study aimed to investigate the effects of hesperetin and nano-hesperetin on neurobehavioral activity and superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GRx) and catalase (CAT) enzymes activity, malondialdehyde (MDA) and glutathione (GSH) levels in hippocampal area of rats in an experimental model of AD. The AD was induced in animals by intracerebroventricular injection of STZ (icv-STZ) unilaterally. Animals were treated with the Hst and nano-Hst (10, 20 mg/kg body weight), then after three successive weeks, recognition memory was examined (passive avoidance test and novel object recognition test) and antioxidant parameters were evaluated. In our study behavioral testes showed improvement on memory retrieval and recognition memory consolidation. Furthermore the Hst and nano-Hst increased the activity of antioxidant enzymes (SOD, glutathione GPx, GRx and CAT) and GSH levels and decreased MDA in the hippocampal area. These results suggested that Hst and nano-Hst may inhibit STZ-induced oxidative stress, and that it may possess therapeutic potential for the treatment of AD.

Neuroprotective Effect of Quercetin Nanocrystal in a 6-Hydroxydopamine Model of Parkinson Disease: Biochemical and Behavioral Evidence.

INTRODUCTION: Studies have suggested that free radicals-induced neurodegeneration is one of the many studies of Parkinson Disease (PD). Quercetin as a natural polyphenol has been regarded as a significant player in altering the progression of neurodegenerative diseases by protecting from damages caused by free radicals. Owing to its poor water solubility, preparation of its oral formulation is urgently needed. Recently, nanocrystal technique as an effective way has been introduced for oral administration of drugs. METHODS: This study investigated the neuroprotective effects of quercetin nanocrystals on 6-hydroxydopamine (6-OHDA)-induced Parkinson-like model in male rats. Quercetin nanocrystals were prepared by the Evaporative Precipitation of Nanosuspension (EPN) method. RESULTS: Administration of quercetin and its nanocrystals (10 and 25 mg/kg) prevented disruption of memory, increased antioxidant enzyme activities (superoxide dismutase and catalase) and total glutathione and reduced Malondialdehyde (MDA) level in the hippocampal area. CONCLUSION: The present study results demonstrated that quercetin nanocrystals with greater bioavailability is effective than quercetin alone in treatment of Parkinson-like model in rat.

Derivation of Pluripotent Cells from Mouse SSCs Seems to Be Age Dependent.

Here, we aimed to answer important and fundamental questions in germ cell biology with special focus on the age of the male donor cells and the possibility to generate embryonic stem cell- (ESC-) like cells. While it is believed that spermatogonial stem cells (SSCs) and truly pluripotent ESC-like cells can be isolated from adult mice, it remained unknown if the spontaneous conversion of SSCs to ESC-like cells fails at some age. Similarly, there have been differences in the literature about the duration of cultures during which ESC-like cells may appear. We demonstrate the possibility to derive ESC-like cells from SSC cultures until they reach adolescence or up to 7 weeks of age, but we point out the impossibility to derive these cells from older, mature adult mice. The inability of real adult SSCs to shift to a pluripotent state coincides with a decline in expression of the core pluripotency genes Oct4, Nanog, and Sox2 in SSCs with age. At the same time genes of the spermatogonial differentiation pathway increase. The generated ESC-like cells were similar to ESCs and express pluripotency markers. In vitro they differentiate into all three germ lineages; they form complex teratomas after transplantation in SCID mice and produce chimeric mice.

Central administration of GPR55 receptor agonist and antagonist modulates anxiety-related behaviors in rats.

G-protein-coupled receptor 55 (GPR55) has been proposed as an atypical cannabinoid receptor, which is activated by lysophosphatidylinositols and some synthetic or endogenous cannabinoid molecules. The exact role of GPR55 receptors in the central nervous system especially in anxiety needs to be evaluated. In this study, the effects of intracerebroventricular (i.c.v.) administration of agonist and antagonist of GPR55 receptor on anxiety-related behaviors in rats were investigated. Here, O-1602 (GPR55 agonist) at the doses of 0.2, 1, and 5 µg/rat increased %OAT and %OAE but not the locomotor activity, showing an anxiolytic response, whereas i.c.v. injection of ML193 (GPR55 antagonist) at the doses of 0.1 and 1 µg/rat increased anxiety-like behaviors while causing locomotor impairment. The antagonistic effect of ML193 on the anxiolytic-like effect of O-1602 was also evaluated. The results showed that ML193 decreased the anxiolytic-like effect of O-1602. Based on these results, it may be concluded that central GPR55 may have a role in modulation of anxiety-like behaviors in rats. Further experiments are needed to elucidate the exact role of these receptors in anxiety.

Identification, determination, and study of antioxidative activities of hesperetin and gallic acid in hydro-alcoholic extract from flowers of Eriobotrya japonica (Lindl.).

OBJECTIVES: Eriobotrya japonica belongs to the Rosaceae. Studies have shown that the flowers of this plant are rich in phenolic and flavonoid compounds. Accorrdingly, the evaluation of antioxidative effects of Eriobotrya japonica Flower Extract (EJFE) have been performed in vitro. MATERIAL AND METHODS: In this study, to investigate the influences of components of EJFE on its antioxidative activity, extract was prepared using hydro-alcoholic (25:75 V/V) solvent and the antioxidative activity of the extract was evaluated based on the scavenging of various radicals (DPPH and H2O2) by spectrophotometric method and chelating of ferrous ions by ferrozine reagent. RESULTS: HPLC analysis of the Eriobotrya japonica Flower Extract (EJFE) revealed hesperetin and gallic acid as the major antioxidants. When the content of total flavonoid and polyphenolic compounds in the flower extract of this plant was examined, a significantly higher level of total polyphenols was found in Eriobotrya japonica flower extract. CONCLUSION: RESULTS demonstrate that the high ability to scavenge free radicals, reducing power, and Fe(+2)chelating activity exerted by the EJFE were due to the high content of hesperetin and gallic acid in the flowers.

Cannabinoid system of the lateral septum in the modulation of anxiety-like behaviors in rats.

BACKGROUNDS: A large body of evidence suggests that the cannabinoid CB1 receptor plays a key role in the regulation of emotional behaviors. The present study was designed to evaluate the effects of CB1 agonist and antagonist on anxiety-like behaviors in the lateral septum (LS) region of the rat brain using elevated plus maze test. METHODS: Rats were anesthetized with ketamine and xylazine and special cannulas were inserted stereotaxically into the LS region. After 1 week of recovery, the effects of intra-LS administration of the CB1 receptor agonist, WIN 55,212-2 and CB1 receptor antagonist, AM251, on %OAT and %OAE were measured. Moreover, the effects of pretreatment with AM251 on the response induced by intra-LS administration of WIN 55,212-2 were also assessed. RESULTS: Intra-LS administration of WIN 55,212-2 (0.001, 0.005 and 0.5µg/rat) decreased the %OAT and %OAE but not locomotor activity, showing an anxiogenic-like response. Intra-LS injection of different doses of AM251 (0.001, 0.01 and 0.1 µg/rat) did not significantly alter the anxiety-like parameters on the plus-maze test. However, intra-LS injections of AM251 (0.01 µg/rat) significantly reversed WIN 55,212-2-induced anxiogenic-like effects. CONCLUSIONS: The results suggest that the cannabinoid system of the lateral septum modulates anxiety-like behavior through CB1 receptor.

The effects of a moderate exercise program on knee osteoarthritis in male wistar rats.

OBJECTIVE(S): Osteoarthritis (OA) or degenerative joint disease is the commonest form of arthritis and can lead to joint pain, decrease in joint's range of motion, loss of function, and ultimately disability. Exercise is considered as one of the non-pharmacological treatments of OA. But the effects of exercise on knee joint cartilage remain ambiguous. The aim of the present study was to investigate the effect of a four-week moderate treadmill exercise on rats' knee osteoarthritis. MATERIALS AND METHODS: Eighteen male Wistar rats (173 ± 1 g, 8 weeks old) were randomly divided into three groups (n = 6): Intact control, monosodium iodoacetate (MIA) only (OA), and training. The osteoarthritis model was induced by intra-articular injection of monosodium iodoacetate (MIA). Subjects followed a moderate-intensity exercise program for 28 days. Rats were killed after 28 days and histological assessment was done on their knee joints. One-way ANOVA (P<0.05) and post-hoc Tukey test was used for the statistical analysis. RESULTS: Histological assessment on 3 measurements of, depth ratio of lesions (P=0.001), total cartilage degeneration width (P=0.001), and significant cartilage degeneration width (P=0.001), demonstrated that moderate exercise for 4 weeks could surprisingly almost treat OA symptoms of rats' knee joints. CONCLUSION: The findings of the present study indicate that a moderate treadmill exercise program exert a beneficial influence on rats' knee osteoarthritis.

In vivo protective effects of gallic acid isolated from Peltiphyllum peltatum against sodium fluoride-induced oxidative stress in rat erythrocytes.

Gallic acid has been identified as an antioxidant component of the edible and medicinal plant Peltiphyllum peltatum. The present study examined its potential protective role against sodium fluoride (NaF)-induced oxidative stress in rat erythrocytes. Oxidative stress was induced by NaF administration through drinking water (1030.675 mg m(-3) for one week). Gallic acid at 10 mg kg(-1) and 20 mg kg(-1) and vitamin C for positive controls (10 mg kg(-1)) were administered daily intraperitoneally for one week prior to NaF administration. Thiobarbituric acid reactive substances, antioxidant enzyme activities (superoxide dismutase and catalase), and the level of reduced glutathione were evaluated in rat erythrocytes. Lipid peroxidation in NaF-exposed rats significantly increased (by 88.8%) when compared to the control group (p<0.05). Pre-treatment with gallic acid suppressed lipid peroxidation in erythrocytes in a dose-dependent manner. Catalase and superoxide dismutase enzyme activities and glutathione levels were reduced by NaF intoxication by 54.4%, 63.69%, and 42% (p<0.001; vs. untreated control group), respectively. Pre-treatment with gallic acid or vitamin C significantly attenuated the deleterious effects. Gallic acid isolated from Peltiphyllum peltatum and vitamin C mitigated the NaF-induced oxidative stress in rat erythrocytes.