Anticancer potential of Ferula assa-foetida and its constituents, a powerful plant for cancer therapy.

Cancer is one of the main challenges of the health system around the world. This disease is increasing in developing countries and imposes heavy costs on patients and governments. On the other hand, despite various drugs, the death rate among cancer patients is still high and the current treatments have many harmful effects. In the traditional medicine of different countries, there are many medicinal plants that can be effective in the treatment of cancer. Ferula plants are traditionally used as spices and food or for medicinal purposes. Ferula assa-foetida is one of the famous plants of this genus, which has been used for the treatment of various diseases since ancient times. Among the main compounds of this plant, we can mention monoterpenes, sulfide compounds and polyphenols, which can show different therapeutic effects. This article has been compiled with the aim of collecting evidence and articles related to the anti-cancer effects of extracts, derived compounds, essential oils and nanoparticles containing Ferula assa-foetida. This review article was prepared by searching the terms Ferula assa-foetida and cancer, and relevant information was collected through searching electronic databases such as ISI Web of Knowledge, PubMed, and Google Scholar. Fortunately, the results of this review showed that relatively comprehensive studies have been conducted in this field and shown that Ferula assa-foetida can be very promising in the treatment of cancer.

Acetylcholinesterase inhibitory activity of Ferula plants and their potential for treatment of Alzheimer's disease.

One of the current strategies in the treatment of Alzheimer's disease is using drugs with acetylcholinesterase (AChE) inhibitory property. The existence of various compounds in plants as a potential source for finding new compounds to treat Alzheimer's disease is a scientific fact. Many secondary metabolites and plant extracts have been reported with the ability to inhibit the AChE activity and improve memory and learning. These compounds can increase the concentration of acetylcholine in the brain and improve cholinergic function in individuals with Alzheimer's disease and reduce the symptoms of this neurological disorder. Plants of Ferula genus are a good source of biologically active compounds such as sesquiterpene derivatives, coumarin derivatives and sulfur-containing compounds. Numerous studies on various extracts or purified compounds of Ferula genus have shown that members of this genus have the inhibitory properties on acetylcholinesterase and can also be effective in improving Alzheimer's and amnesia. This review article summarizes studies on plants of Ferula extracts and their derived compounds to find AChE inhibitors.

Calcium dobesilate ameliorates hepatorenal injury induced by carbon tetrachloride in mice.

Objectives: Calcium dobesilate (CaD) has anti-oxidant, anti-inflammatory, and anti-apoptotic effects. In this study, the protective effects of CaD against hepatorenal damage induced by carbon tetrachloride (CCl4) in mice were evaluated. Materials and Methods: Thirty male mice were randomly divided into five groups: Control, CaD 100 mg/kg, CCl4, CCl4+CaD 50 mg/kg, and CCl4+CaD 100 mg/kg. CaD (50 and 100 mg/kg) was administered orally once a day for 4 weeks. The liver and kidney indices (serum creatinine, blood urine nitrogen, alanine aminotransferase, and aspartate aminotransferase levels) were determined. Also, liver and kidney tissue oxidant/anti-oxidant markers (glutathione peroxidase, malondialdehyde, total anti-oxidant capacity, and superoxide dismutase) were measured. Cleaved caspase-3, Bax, cytochrome-c, and Bcl-2 protein levels were measured by immunoblotting method in the liver and kidney tissues. The liver and kidney histopathological changes were evaluated by the Hematoxylin and Eosin (H&E) staining method. Results: CCl4 induced significant oxidative stress and apoptosis in kidney and liver tissues that was concomitant with histopathological abnormalities in these organs in the CCl4 group versus the control (P<0.05). However, CaD (100 mg/kg) could significantly improve the histopathological change in the liver and kidney tissues of CCl4+CaD 100 mg/kg mice versus the CCl4 group (P<0.05). In addition, CaD (100 mg/kg) attenuated the pro and anti-apoptotic markers in the liver and kidney tissues of CCl4+CaD 100 mg/kg mice versus the CCl4 group (P<0.05). Conclusion: CaD (100 mg/kg) has a protective effect against hepatorenal injury induced by CCl4 at least via its anti-apoptotic and anti-oxidant properties.

Chronic treatment with coenzyme Q10 mitigates the behavioral dysfunction of global cerebral ischemia/reperfusion injury in rats.

Objectives: The Ischemia/reperfusion (I/R) phenomenon has a critical role in brain injuries induced by some kinds of stroke. The current study investigates the effects of Coenzyme Q10 (Q10) on global cerebral I/R in rats. Materials and Methods: Fifty male Wistar rats were used in this study. The global cerebral I/R was induced by obstructing both common carotid arteries for 20 min and the animals were treated with Q10 (200 mg/kg; PO.) for 6 weeks. Depressive and anxiety-like behaviors were assessed using the elevated plus-maze and forced swimming test, respectively. Working and spatial learning and memory were assessed by the Y-maze continuous alternation task and Morris water maze. The brain tissues were evaluated for brain edema, brain-derived neurotrophic factor (BDNF) levels, and superoxide dismutase (SOD) activities. Results: Our results indicated that global cerebral I/R increased anxiety and depression-like behavior as well as reduced cognitive performance. Moreover, the levels of BDNF and activities of SOD are reduced in stroke animals. Chronic post-stroke treatment with Q10 decreased brain edema. Furthermore, Q10 administration reduced anxiety and depressive-like behavior as well as cognitive impairments in stroke animals. Q10 also increased the SOD activities and BDNF levels in the brain tissues of stroke animals. Conclusion: Finally, we can conclude that using Q10 supplementation may be beneficial against the global cerebral I/R complications.

Ischemic post-conditioning is neuroprotective even at delayed tPA administration after embolic stroke in female rats.

Objectives: Delayed tissue plasminogen activator (tPA) thrombolysis is accompanied by different complications in stroke patients. Studies reported sex differences in stroke therapy. Ischemic postconditioning (PC) unveils neuroprotection in stroke models. In this study, we investigate the combined effect of delayed tPA therapy and PC procedure during an embolic stroke experimental model in female rats. Materials and Methods: Female Wistar rats were randomly divided into control (saline), tPA, PC, and tPA+PC groups after stroke induction via clot injection to the middle cerebral artery. tPA treatment was initiated 6 hr after stroke, and PC procedure was performed 6.5 hr post-ischemia induction (occlusion: 10 sec; reopening: 30 sec; 5 cycles). The cerebral blood flow (CBF) was recorded up to 60 min from IV tPA injection time. The parameters of brain edema, infarct volume, disruption of the blood-brain barrier (BBB), behavioral tests, and matrix metalloproteinases-9 (MMP-9) were evaluated. Results: This study revealed that PC conduction prevents excessive CBF increase by tPA and played a protective role in infarct volume reduction (P<0.05). The combination of PC and tPA reduced the infarct volume, brain edema, and protected BBB. tPA+PC could alleviate neurobehavioral disorders compared with control or tPA. Moreover, PC had the capability of MMP-9 reduction when combined with delayed tPA (P<0.05). Conclusion: Conduction of PC not only alleviated some stroke complications but also enhanced the therapeutic time window of tPA in female rats under embolic stroke.

Modulatory Effects of Memantine on Neuronal Response Properties in Rat Barrel Cortex.

Introduction: Memantine as N-Methyl-D-Aspartic Acid (NMDA) receptor antagonist is used in some neurological disorders. Moreover, memantine presents modulatory effects on the somatosensory information processing in healthy subjects. This study investigated the effects of memantine on electrophysiological properties of barrel cortex neurons in male rats. Methods: Single unit recording was used to evaluate the electrophysiological properties of barrel cortex neurons. The neural responses to the Principal Whisker (PW), Adjacent Whisker (AW), and combined displacement of two whiskers [20 ms Inter-Stimulus Intervals (ISIs)] were recorded before and 2 hours after memantine gavage (10 mg/kg). A Condition Test Ratio (CTR) was calculated for assessing inhibitory interactions. Results: Two hours after memantine gavage, neuronal ON and OFF responses to PW deflection were decreased. Furthermore, CTR for both ON and OFF responses was decreased following memantine administration. Conclusion: The current study demonstrated that memantine modified neural response properties in the rat barrel cortex. Highlights: Memantine modulated excitatory receptive fields in the rat somatosensory cortex.Memantine decreased integrative receptive fields in rat somatosensory cortex. Plain Language Summary: As an NMDA receptor antagonist, memantine is used to treat moderate to severe Alzheimer's disease. Memantine has beneficial effects on cognition, mood, and perform daily activities. However, the current study results suggested that memantine may affect information processing in the somatosensory system. This should be considered for future research in the clinic.

The effect of intra-striatal administration of GPR55 agonist (LPI) and antagonist (ML193) on sensorimotor and motor functions in a Parkinson's disease rat model.

OBJECTIVE: G protein-coupled receptor 55 (GPR55) is an orphan G protein-coupled receptor with various physiological functions. Recent evidence suggests that this receptor may be involved in the control of motor functions. Therefore, in the present study, we evaluated the effects of intra-striatal administration of GPR55 selective ligands in a rat model of Parkinson's disease. METHODS: Experimental Parkinson was induced by unilateral intra-striatal administration of 6-hydroxydopamine (6-OHDA, 10 µg/rat). L-α-lysophosphatidylinositol (LPI, 1 and 5 µg/rat), an endogenous GPR55 agonist, and ML193 (1 and 5 µg/rat), a selective GPR55 antagonist, were injected into the striatum of 6-OHDA-lesioned rats. Motor performance and balance skills were evaluated using the accelerating rotating rod and the ledged beam tests. The sensorimotor function of the forelimbs and locomotor activity were assessed by the adhesive removal and open field tests, respectively. RESULTS: 6-OHDA-lesioned rats had impaired behaviours in all tests. Intra-striatal administration of LPI in 6-OHDA-lesioned rats increased time on the rotarod, decreased latency to remove the label, with no significant effect on slip steps, and locomotor activity. Intra-striatal administration of ML193 also increased time on the rotarod, decreased latency to remove the label and slip steps in 6-OHDA-lesioned rats mostly at the dose of 1 µg/rat. CONCLUSIONS: This study suggests that the striatal GPR55 is involved in the control of motor functions. However, considering the similar effects of GPR55 agonist and antagonist, it may be concluded that this receptor has a modulatory role in the control of motor deficits in an experimental model of Parkinson.

Long-term metformin therapy improves neurobehavioral functions and antioxidative activity after cerebral ischemia/reperfusion injury in rats.

Metformin (MET),an antidiabetic drug, has shown antioxidative and neuroprotective effects. In the present investigation, we aimed to study the probable effects of MET on cerebral ischemia/reperfusion in rats. Rats underwent cerebral ischemia/reperfusion and MET was administered orally at doses of 100 and 200 mg/kg for 56 days. Anxiety- and depressive-like behaviors were evaluated by elevated plus-maze or forced swimming tests, respectively. was assessed by. Cognitive functions were assessed by Y-maze continuous alternation task and morris water maze. The activity of SOD and the level of BDNF were measured in brains samples. Our results showed that administration of 200 mg/kg MET reduced the percent of brain edema (84.00 ± 2.13) in comparison with the ischemic animals (91.25 ± 2.25) (p < 0.05). Administration of 200 mg/kg MET in ischemic animals improved anxiety-like behavior by increasing the percentage of the open arms entries (46.51 ± 3.13) and the percentage of the open arms time (32.70 ± 2.49) in comparison with the cerebral ischemia group (26.35 ± 7.02 and 15.32 ± 5.78, respectively) (all p < 0.001). MET treatment (200 mg/kg) increased the cognition index of correct alternations (90.20 ± 4.95) in comparison with the cerebral ischemia group (59.50 ± 8.01) (p < 0.05). MET at the both doses reduced escape latency compared to the cerebral ischemia animals (all p < 0.05). In addition, 200 mg/kg MET increased the time spent in the target quadrant (16.06 ± 0.58) in comparison with the ischemic animals (9.84 ± 0.92) (p < 0.001) and the both doses of the drug increased the number of crossing (5.42 ± 0.36 and 6.5 ± 0.42, respectively) compared to the cerebral ischemia group (3.75 ± 0.31) (p < 0.05 and p < 0.001, respectively). Moreover, 200 mg/kg MET reduced the immobility time (47.50 ± 9.00) in comparison with the cerebral ischemia group (93.43 ± 8.28) (p < 0.001). Furthermore, the both doses of MET increased the BDNF levels (4590 ± 197.6 and 4767 ± 44.10, respectively) in comparison with the ischemic animals (3807 ± 42.56) (p < 0.01 and p < 0.001, respectively). Also, the both doses of the drug increased the SOD activity of brain (52.67 ± 0.33 and 55.00 ± 0.57, respectively) compared to the ischemic animals (49.33 ± 0.33) (p < 0.01 and p < 0.001, respectively). Based on our data, long-term MET therapy may improve behavioral disorders following cerebral ischemia/reperfusion and can be considered as a novel therapeutic approach for the treatment of brain ischemic conditions.

Ceftriaxone improves senile neurocognition damages induced by D-galactose in mice.

OBJECTIVES: Ceftriaxone (Cef), a beta-lactam antibiotic, is accompanied by antioxidant and anti-inflammatory properties. It has been shown that Cef has beneficial effects on Alzheimer's disease. In the current investigation, the effect of Cef in a mice model of aging was investigated. MATERIALS AND METHODS: Forty male mice were equally aliquoted into four groups as follows: Control (as healthy normal animals), D-galactose (DG) group (treated with 500 mg/kg/day DG for 6 weeks), DG + Cef group (treated with DG plus Cef 200 mg/kg/day for 6 weeks), and Cef group (treated with Cef 200 mg/kg/day for 6 weeks). A battery of behavioral tests was done to evaluate age-related neurocognitive changes. The activities of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD), as well as the level of malondialdehyde (MDA) in the brain, were measured by biochemical methods. Also, to determine the brain damage, histopathological alterations in the hippocampus were measured using hematoxylin and eosin (H&E) staining. RESULTS: Our results indicate that neurobehavioral dysfunctions of DG can be prevented by co-administration of Cef. We also found that Cef increases the activity of SOD, GPx, and CAT as well as decreasing the level of MDA in the brain of aged mice. CONCLUSION: Based on our findings, Cef declines neurocognitive dysfunctions in the DG-induced model of aging, possibly through its antioxidative properties.

Whole body hypothermia extends tissue plasminogen activator treatment window in the rat model of embolic stroke.

Late treatment with tissue plasminogen activator (tPA) leads to reperfusion injury and poor outcome in ischemic stroke. We have recently shown the beneficial effects of local brain hypothermia after late thrombolysis. Herein, we investigated whether transient whole-body hypothermia was neuroprotective and could prevent the side effects of late tPA therapy at 5.5 h after embolic stroke. After induction of stroke, male rats were randomly assigned into four groups: Control, Hypothermia, tPA and Hypothermia+tPA. Hypothermia started at 5 h after embolic stroke and continued for 1 h. Thirty min after hypothermia, tPA was administrated. Infarct volume, brain edema, blood-brain barrier (BBB) and matrix metalloproteinase-9 (MMP-9) were assessed 48 h and neurological functions were assessed 24 and 48 hour post-stroke. Compared with the control or tPA groups, whole-body hypothermia decreased infarct volume (P < 0.01), BBB disruption (P < 0.05) and MMP-9 level (P < 0.05). However, compared with hypothermia alone a combination of hypothermia and tPA was more effective in reducing infarct volume. While hypothermia alone did not show any effect, its combination with tPA reduced brain edema (P < 0.05). Hypothermia alone or when combined with tPA decreased MMP-9 compared with control or tPA groups (P < 0.01). Although delayed tPA therapy exacerbated BBB integrity, general cooling hampered its leakage after late thrombolysis (P < 0.05). Moreover, only combination therapy significantly improved sensorimotor function as well as forelimb muscle strength at 24 or 48 h after stroke (P < 0.01). Transient whole-body hypothermia in combination with delayed thrombolysis therapy shows more neuroprotection and extends therapeutic time window of tPA up to 5.5 h.

Ameliorating effect of troxerutin in unilateral ureteral obstruction induced renal oxidative stress, inflammation, and apoptosis in male rats.

Unilateral ureteral obstruction (UUO) induces renal injury and troxerutin attenuates the inflammatory parameters and decreases oxidative stress. Accordingly, this study explored the renoprotective effect of troxerutin in UUO-induced renal oxidative stress, inflammation, and apoptosis in male Wistar rats. Animals were randomly separated into five groups (n = 8): control, UUO, and three UUO groups treated with troxerutin (1, 10, and 100 mg/kg). UUO-induced and vehicle/troxerutin administration was continued for 3 days. Then serum creatinine, mean arterial pressure (MAP), renal perfusion pressure (RPP), renal vascular resistance (RVR), and renal blood flow (RBF) were measured. Superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase activities, total antioxidant capacity (TAC), and malondialdehyde (MDA) levels as some oxidative stress parameters were measured in the left kidney. The immunoblotting method was applied to evaluate the cleaved caspase-3 Bax, Bcl-2, and TNF-α proteins level. The hematoxylin and eosin method was used to assess the kidney tissue damage score (KTDS). In 3 days, UUO significantly increased serum creatinine level, KTDS, RVR, MDA, Bax, cleaved caspase-3, and TNF-α protein levels (p < 0.05); and decreased RBF, TAC, SOD, catalase, GPx activity levels and Bcl-2 protein expression level in the left kidney (p < 0.05). Troxerutin (100 mg/kg) significantly attenuates the indicators alteration induced by UUO. Our findings represented that the renoprotective effect of troxerutin may be related to its anti-oxidative stress, anti-inflammation, anti-apoptosis, and RBF improver properties.

The effect of oleuropein on unilateral ureteral obstruction induced-kidney injury in rats: the role of oxidative stress, inflammation and apoptosis.

Unilateral ureteral obstruction (UUO) induces kidney injury. Oleuropein as a major compound of olive leaves modulates the inflammatory parameters and decreases oxidative stress. Accordingly, we evaluate the renoprotective effect of oleuropein against 3-day UUO rats. Forty rats were randomly divided into five groups (n = 8) including control, UUO and UUO + oleuropein groups (50, 100 and 200 mg/kg). UUO model was induced by left ureter ligation and continued for 3-day. Rats were treated synchronic daily for 3-day, then mean arterial pressure (MAP), renal perfusion pressure (RPP), renal blood flow (RBF), serum creatinine level, and also superoxide dismutase (SOD), glutathione peroxidase (GPx) activity levels and malondialdehyde (MDA) concentration (in the obstructed kidney) were measured. The western blotting method was applied to evaluate the Bax, Bcl-2, cleaved caspase-3 and TNF-α proteins expression level. The hematoxylin and eosin method was applied to evaluate the kidney tissue damage score (KTDS). UUO significantly increased RVR, KTDS, and MDA, cleaved caspase-3, Bax, serum creatinine and TNF-α protein levels (P < 0.05), and also significantly decreased RBF, SOD, and GPx and Bcl-2 protein expression levels (P < 0.001) in the obstructed kidney and oleuropein (200 mg/kg) significantly ameliorated the changes induced by UUO. Our findings showed that oleuropein has a renoprotective effect against 3-day UUO. The mechanisms underlying the observed effects may be related to its antioxidative stress, anti-apoptotic, and anti-inflammatory effects.

Protective effects of Vitex agnus-castus in ovariectomy mice following permanent middle cerebral artery occlusion.

OBJECTIVES: Previous studies have indicated that phytoestrogens induce estrogenic as well as anti-inflammatory effects, and they are found in high abundance in the extracts of some herbs such as Vitex Agnus Castus (VAC). Therefore, we investigated the effect of VAC extract on ovariectomized mice after the induction of permanent middle cerebral artery occlusion (PMCAO) model. MATERIALS AND METHODS: In this study, 50 mice ranging from 25 to 35 g were divided into five experimental groups as follows: Control, VAC, Estrogen, Tamoxifen, and Tamoxifen-VAC. Animals were ovariectomized, and after 30 days of treatment, they were given PMCAO induction. Behavioral assessment (adhesive removal and wire hanging tests) was evaluated 24 hr, 48 hr, and one week after induction of stroke. The infarct volume, as well as serum levels of matrix metalloproteinase-9 (MMP-9) and interleukin-10 (IL-10), were measured one week after stroke. RESULTS: One week after stroke, in both VAC and estrogen groups, the infarct size reduced in comparison with the control group. Estrogen and VAC extract improved adhesive removal and wire hanging test, increased the level of IL-10, and decreased the level of MMP-9 compared with the control group. In addition, co-administration of tamoxifen and VCA extract had no significant effect on measured indices compared with control and tamoxifen groups. CONCLUSION: Based on our findings, VAC extract has neuroprotective properties and can reduce stroke injuries in PMCAO-induced ovariectomized mice via anti-inflammatory and estrogenic properties.

Pro-neurocognitive and anti-sarcopenic benefits of one-year metformin therapy in ovariectomized aged mice.

Health promotion and healthy nutrition significantly increased life expectancy around the world. Aging is associated with an increase in age-related diseases. The use of metformin (Met) as an anti-aging drug has recently been proposed based on its widespread use in clinical practice. Reports have shown that Met acts as an anti-aging agent. In this study, the effects of long-term, 1 year, Met administration on aging-related behaviors and longevity in ovariectomized mice was studied. Met (1 and 10 mg/kg, daily) was administered orally in ovariectomized mice. The anxiety-like behavior, working memory, and physical strength were measured through elevated plus maze, Y-maze, vertical grid holding, and the obligatory swimming capacity tests. Brains were harvested to measure brain-derived neurotrophic factor (BDNF) level. Also, the Kaplan-Meier survival curves were used to show differences and similarities in survival patterns. Met (10 mg/kg) decreased anxiety-like behaviors as well as increased muscle strength and working memory in the ovariectomized mice. Moreover, Met increased the physical strength and longevity as well as the level of BDNF in the ovariectomized mice. Our results indicate that Met administration can be an effective strategy for having a healthy aging in the absence of female gonadal hormones and reverses deleterious effects of ovariectomy-induced aging possibly through BDNF.

Effect of oleuropein on morphine-induced hippocampus neurotoxicity and memory impairments in rats.

Oleuropein, as an olive leaf extract antioxidant polyphenol, has been reported to be a free radical scavenger. This study was done to investigate the effects of oleuropein, against morphine-induced hippocampus neurotoxicity and memory impairment in rats. The Morris water maze (MWM) test was used to assess the effect of oleuropein (5, 15, and 30 mg/kg, i.p., co-administrated with morphine) on spatial learning and memory of male Wistar rats which were treated with morphine sulfate (45 mg/kg, s.c., 4 weeks). In order to evaluate the cleaved caspase-3, Bax, and Bcl2 protein expression (as biochemical markers of apoptosis) in CA1 area of hippocampus tissue, the western blot test was used. Also, to evaluate the oxidative stress status of hippocampus CA1 area tissue, the malondialdehyde (MDA) level, superoxide dismutase (SOD) activity, and glutathione peroxidase (GPx) activity were assessed. The data showed that oleuropein treatment (15 and 30 mg/kg) improves the spatial learning and memory impairments in morphine-treated animals. Also, oleuropein treatment decreased the apoptosis and oxidative stress levels in the hippocampus CA1 area of morphine-treated rats. Oleuropein can prevent the spatial learning and memory impairments in morphine-treated rats. Molecular mechanisms underlying the observed effects could be at least partially related to the inhibition of neuronal apoptosis and oxidative stress in the hippocampus CA1 area of morphine-treated rats.

Treatment with troxerutin protects against cisplatin-induced kidney injury in mice.

BACKGROUND: Cisplatin (CP) is a synthetic and anticancer drug, and one of the major side effects of CP is nephrotoxicity. This study was done to evaluate the renoprotective effects of troxerutin (Tro) in nephrotoxicity induced by CP in male mice. METHODS: In this experimental study, 28 male mice were divided randomly into four groups. Mice were treated with CP (20 mg/kg, i.p.) then Tro (75 and 150 mg/kg/day, po) was administered for three consecutive days. Blood samples were collected to determine serum creatinine (Cr) and blood urea nitrogen (BUN) levels. The kidney tissues were used for histological examination and biochemical assays. Malondialdehyde (MDA) level, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity were assessed in renal tissue. RESULTS: Results showed a significant increase in the Cr, BUN and MDA levels and a significant decrease in the renal SOD and GPx activity by CP administration. Treatment with Tro for three consecutive days attenuated these changes. Also, the renoprotective effect of the Tro was confirmed by the histological examination of the kidneys. CONCLUSIONS: Our results demonstrated that Tro has protective effects against CP-induced nephrotoxicity through improving the biochemical indices and the oxidative stress parameters.

The effect of the anti-diabetic drug metformin on behavioral manifestations associated with ovariectomy in mice.

The aim of this study was to evaluate the anti-diabetic drug metformin (Met) effects on the anxiety and cognitive impairment in ovariectomized mice. Thirty-two female adult mice were distributed into four groups: control, sham ovariectomy, ovariectomy + Met 7 mg/kg and ovariectomy + Met 15 mg/kg. The vaginal cytology was used to confirm the ovariectomy surgery. Anxiety was monitored using elevated plus maze test and cognitive function was assessed by novel object recognition task. Animal's brains were analyzed for the brain-derived neurotrophic factor (BDNF). Our results demonstrated that ovariectomy caused cognitive impairments and anxiety, as well as decreased BDNF levels. Moreover, administration of Met improves ovariectomy-related disorders such as cognitive impairments and anxiety, as well as increased BDNF levels. The results of the present study suggest that Met could be used as a novel therapeutic strategy for the treatment of ovariectomy-related conditions.

Ascorbic acid attenuates cognitive impairment and brain oxidative stress in ovariectomized mice.

BACKGROUND: Menopause is associated with increased oxidative stress and memory impairment. Based on the antioxidant property of ascorbic acid (AA), It's effect on cognitive function, the serum level of the brain-derived neurotrophic factor (BDNF) and the activity of antioxidant enzymes within the brain in ovariectomized (OVX) mice was investigated. METHODS: AA (100, 300 and 500 mg/kg), was orally administrated per day in OVX mice for 30 days. Tactile learning and working memory were evaluated by the novel object recognition task and T-maze continuous alternation task, respectively. The levels of serum BDNF were measured and animals' brains were analyzed for the superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity. RESULTS: AA prevented from the deleterious effects of ovariectomy on learning memory (300 and 500 mg/kg) and working memory (100 and 500 mg/kg). The serum BDNF level was also increased in OVX animals treated with AA (100 and 500 mg/kg). Furthermore, AA (500 mg/kg) increased the SOD and GPx activity in the brain of OVX animals. CONCLUSIONS: Collectively, the results of the present study suggest that AA might be an appropriate choice in loss or reduction of estradiol for the amelioration of cognitive impairment.

CX691, as an AMPA receptor positive modulator, improves the learning and memory in a rat model of Alzheimer's disease.

OBJECTIVES: Growing evidence suggests that dysfunction of the glutamatergic system and α-amino-3-hydroxy-5-methyl-4-isoazolepropionic acid (AMPA) receptors are involved in pathology of Alzheimer's disease (AD). Because AMPA receptors play a key role in plasticity synaptic regulation, positive modulation of these receptors may rescue the cognitive deficits in the AD. The aim of this study was to explore the effect of CX691, a specific positive allosteric modulator of the AMPA-type glutamate receptors (Ampakine), on spatial learning and memory in a rat model of AD. MATERIALS AND METHODS: For induction of AD, amyloid-beta 1-42 (Aß1-42) was microinjected into the hippocampus of male Wistar rats (250-300 g). The Morris water maze (MWM) test was used to evaluate the effect of CX691 (0.03 and 0.3 mg/kg, twice a day for 10 days, orally) on spatial learning and memory of rats. In order to evaluate the protein expression of brain-derived neurotrophic factor (BDNF) in hippocampus tissue, ELISA test was used. RESULTS: The obtained data showed that treatment with CX691 (0.3 mg/kg) improves the impairment of spatial learning and memory in AD rats. Also, treatment with CX691 (0.3 mg/kg), increased the BDNF protein level in hippocampus tissue of AD rats compared to non-treated animals. CONCLUSION: The CX691 can improve the BDNF protein expression as well as spatial performance of learning and memory in AD rats.

Heterogeneous effects of cholecystokinin on neuronal response properties in deep layers of rat barrel cortex.

Cholecystokinin (CCK) is one of the most studied neuropeptides in the brain. In this study, we investigated the effects of CCK-8s and LY225910 (CCK2 receptor antagonist) on properties of neuronal response to natural stimuli (whisker deflection) in deep layers of rat barrel cortex. This study was done on 20 male Wistar rats, weighing 230-260 g. CCK-8s (300 nmol/rat) and LY225910 (1 µmol/rat) were administered intracerebroventricularly (ICV). Neuronal responses to deflection of principal (PW) and adjacent (AW) whiskers were recorded in the barrel cortex using tungsten microelectrodes. Computer controlled mechanical displacement was used to deflect whiskers individually or in combination at 30 ms inter-stimulus intervals. ON and OFF responses for PW and AW deflections were measured. A condition-test ratio (CTR) was computed to quantify neuronal responses to whisker interaction. ICV administration of CCK-8s and LY225910 had heterogeneous effects on neuronal spontaneous activity, ON and OFF responses to PW and/or AW deflections, and CTR for both ON and OFF responses. The results of this study demonstrated that CCK-8s can modulate neuronal response properties in deep layers of rat barrel cortex probably via CCK2 receptors.