crocin and Memory-Disorders

Large evidence has shown that cholestasis has a wide-range of deleterious effects on brain function, and also, on neurocognitive functions including learning and memory. On the other hand, crocin (derived from Crocus sativus) is a medicinal natural compound that induces neuroprotective and precognitive effects. In this study, we aimed to evaluate the effect of crocin on spatial learning and memory in cholestatic rats with respect to the level of mitochondrial transcriptional factor A (TFAM), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), catalase (CAT), and superoxide dismutase (SOD) in the hippocampus of male Wistar rats. Bile duct ligation (BDL) was used to induce cholestasis. Y-maze apparatus was used to assess spatial memory performance and real-time PCR was used to assess TFAM and PGC-1α gene expression. Also, crocin was injected intraperitoneal at the doses of 15, 20, and 30 mg/kg for thirty days. The results showed that BDL impaired spatial memory in rats. BDL also decreased SOD, TFAM, and PGC-1α level. In addition, crocin partially reversed the impairment effect of BDL on spatial memory. Crocin (30 mg/kg) also reversed the effect of BDL on SOD, TFAM, and PGC-1α. Of note, the effect of BDL on CAT activity was controversial. It seems that BDL can increase CAT activity. In addition, crocin (30 mg/kg) reversed the enhancement of CAT following BDL to its control level. In conclusion, crocin may induce a significant neuroprotective effect on cholestasis-induced memory impairment.

Topics: Animals; Antioxidants; Catalase; Cholestasis; Hippocampus; Male; Memory Disorders; Rats; Rats, Wistar; Spatial Memory; Superoxide Dismutase; Transcription Factors

The aim of the current study was to investigate the probable mechanism and effect of crocin on brain oxidative damage and memory deficits induced by unpredictable chronic mild stress (UCMS).. Male Wistar rats were randomly divided into six groups consisting of one vehicle group (received normal saline), four groups included rats who received UCMS 4 weeks out of which three groups were pretreated with different doses of crocin (10, 20, and 30 mg/kg/day) concomitantly. To assess the pure effect of crocin, the last experimental group received a high dose of crocin (30 mg/kg/day) without exposure to the UCMS procedure. The behavioral tests including Morris water maze (MWM) and passive avoidance (PA) were performed and eventually they were sacrificed for the estimation of biochemical parameters.. The increase in Malondialdehyde (MDA) as an oxidative stress indicator and nitrite levels in the hippocampus were observed in UCMS rats, along with memory deficits in behavioral tests including passive avoidance and Morris water maze (MWM) test. Moreover, treatment with crocin decreased MDA, nitrite, pro-inflammatory cytokine such as TNF-α, and pathological hallmark of Alzheimer's disease including amyloid-β (Aβ), and glial fibrillary acidic protein (GFAP) in the hippocampus, whereas antioxidant agents including total thiol content, SOD, and catalase activity were increased. Also behavioral test demonstrated a positive effect of crocin on memory deficit induced by UCMS. Interlukin-10 as an important anti-inflammatory agent was increased as well. Interestingly, in some behavioral and biochemical findings, treatment with 30 mg/kg of crocin has given better results compared to vehicle group, which means the administration of crocin could have preventive effects on learning and memory impairment.. The present study strongly confirmed the positive effect of crocin and has the potential as an antioxidant and anti-inflammatory agent that could improve memory impairment induced by UCMS.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Cognitive Dysfunction; Male; Maze Learning; Memory Disorders; Neuroinflammatory Diseases; Nitrites; Oxidative Stress; Rats; Rats, Wistar

Crocin and Terminalia chebula (T. chebula) were proven to have neuroprotective effects. In this study, we evaluated the preventive effects of crocin and alcoholic extract of the T. chebula alone and in combination to examine their efficacy against chronic restraint stress (CRS)‑induced cognitive impairment, anxiety‑like behaviors, hippocampal synaptic plasticity deficit as well as neuronal arborization damage in the hippocampal CA1 neurons. Over 14 consecutive days, animals received crocin, T. chebula, or their combination (5 min before CRS). The elevated plus‑maze results showed that crocin and T. chebula alone and in combination treatment significantly increased the time spent in open arms, percentage of open arm entries, and head dipping as compared with the CRS group. Barnes maze results showed that administration of crocin and T. chebula alone and their combination significantly improves spatial memory indicators such as distance traveled, latency time to achieving the target hole, and the number of errors when compared to the CRS group. These learning deficits in CRS animals correlated with a reduction of long-term potentiation (LTP) in hippocampal CA1 synapses, which both T. chebula and crocin treatment improved field excitatory postsynaptic potentials (fEPSP) amplitude and fEPSP slope reduction induced by CRS. Golgi‑Cox staining showed that T. chebula and crocin treatment increased the number of dendrites and soma arbors in the CA1 neurons compared with the CRS group. Our results suggest that both T. chebula and crocin attenuated CRS‑induced anxiety‑like behaviors, memory impairment, and synaptic plasticity loss in hippocampal CA1 neurons. We found no significant difference between single treatments of T. chebula or crocin and their combination in protecting CRS‑induced anxiety‑like behaviors, memory impairment, and synaptic plasticity loss in hippocampal CA1 neurons.

Topics: Animals; Carotenoids; Hippocampus; Male; Memory Disorders; Neuronal Plasticity; Rats; Spatial Memory; Terminalia

Adolescent chronic stress has been shown to induce functional, biochemical and morphological modifications of the hippocampus, leading to stress-related disorders in adulthood. The present study investigated the effects of exercise, crocin and their combination on spatial learning and memory impairment and dendritic retraction of the CA3 pyramidal neurons induced by chronic adolescent stress in adult male rats. Rats were exposed to restraint stress 2 h/day for 10 days during postnatal days (PNDs) 30-40. Following this period, separate groups of animals were treated with crocin (25 and 50 mg/kg), exposed to running wheel, and or received the combined treatment during PNDs 41-55. Following the interventions, plasma levels of corticosterone, spatial learning and memory, apical dendritic length of CA3 pyramidal neurons and BDNF levels in the CA3 area were assessed. Findings showed that adolescent stress significantly increased corticosterone levels and caused a tendency to reduce CA3 BDNF levels. Adolescent stress also impaired spatial learning and memory, and retracted apical dendritic length of CA3 pyramidal neurons. Crocin, voluntary exercise, and their combination recovered stress-induced spatial learning and impairment and CA3 pyramidal neurons dendritic length retraction. All treatments also reduced significantly corticosterone levels and enhanced CA3 BDNF levels in the stress groups. Finally, these treatments even increased apical dendritic length of CA3 pyramidal neurons in the non-stress groups. These findings indicate that detrimental effects of adolescent stress on cognitive function and hippocampal morphology in adulthood could be restored by early interventions with physical activity and crocin treatment during adolescent period.

Topics: Animals; Carotenoids; Dendrites; Hippocampus; Male; Memory; Memory Disorders; Physical Conditioning, Animal; Rats, Wistar; Restraint, Physical; Spatial Navigation; Stress, Psychological

Topics: Anesthetics; Animals; Carotenoids; Crocus; Humans; Ketamine; Memory; Memory Disorders; Rats

Anxiety, hippocampus synaptic plasticity deficit, as well as pro-inflammatory cytokines, are involved in Alzheimer's disease (AD). The present study is designed to evaluate the possible therapeutic effect of crocin on anxiety-like behaviours, hippocampal synaptic plasticity and neuronal shape, as well as pro-inflammatory cytokines in the hippocampus using in vivo amyloid-beta (Aβ) models of AD. The Aβ peptide (1-42) was bilaterally injected into the frontal-cortex. Five hours after the surgery, the rats were given intraperitoneal (IP) crocin (30 mg/kg) daily up to 12 days. Elevated plus maze results showed that crocin treatment after bilateral Aβ injection significantly increased the percentage of spent time into open arms, frequency of entries, and percentage of entries into open arms as compared with the Aβ group. In the open field test, the Aβ+crocin group showed a higher percentage of spent time in the centre and frequency of entries into central zone as compare with the Aβ treated animals. Administering crocin increased the number of soma, dendrites and axonal arbores in the CA1 neurons among the rats with Aβ neurotoxicity. Cresyl violet (CV) staining showed that crocin increased the number of CV-positive cells in the CA1 region of the hippocampus compared with the Aβ group. Silver-nitrate staining indicated that crocin reduced neurofibrillary tangle formation induced by Aβ. Crocin treatment attenuated the expression of TNF-α and IL-1β mRNA in the hippocampus compared with the Aβ group. Our results suggest that crocin attenuated Aβ-induced anxiety-like behaviours and neuronal damage, and synaptic plasticity loss in hippocampal CA1 neurons may via its anti-inflammatory effects.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Carotenoids; Hippocampus; Male; Memory Disorders; Neurons; Peptide Fragments; Rats

Sleep deprivation (SD) induces cognitive impairments such as memory deficit. Brain-derived neurotrophic factor (BDNF) is considered as the most critical neurotrophin in the central nervous system that is involved in sleep and memory. The main receptor of BDNF, tropomyosin receptor kinase B (TrkB), is dramatically expressed in the hippocampus. Also, extracellular signal-regulated kinase (ERK) has a significant role in memory function. Crocin is a carotenoid chemical compound and the active component of the flower. In this research, we aimed to investigate the effect of total SD (TSD, 24 h) and crocin on memory performance, and BDNF, TrkB and ERK hippocampal levels.. Passive avoidance memory was assessed using step-through, and working memory was measured using Y-maze tasks. The level of proteins in both hemispheres of the hippocampus was evaluated using Western blotting. Crocin was injected intraperitoneally at doses of 1, 5 and 15 mg/kg.. Twenty-four-hour TSD impaired both types of memories and decreased the level of all proteins in both hemispheres of the hippocampus. Crocin at all doses restored TSD-induced memory deficits. Crocin (15 mg/kg) reversed the effect of TSD on levels of all proteins.. The adverse effect of TSD on the level of proteins in the hippocampus may disrupt synaptic plasticity and transmission, which induces memory impairment. Additionally, the restoration effect of crocin on the decrease in protein levels may be involved in its improvement effect on memory performance.

Topics: Animals; Brain-Derived Neurotrophic Factor; Carotenoids; Dose-Response Relationship, Drug; Extracellular Signal-Regulated MAP Kinases; Hippocampus; Male; Maze Learning; Memory Disorders; Neuronal Plasticity; Rats; Rats, Wistar; Receptor, trkB; Sleep Deprivation

Aim While stress causes brain dysfunction, crocin (as an active component of saffron) and exercise (as part of a healthy lifestyle) improve stress-induced memory impairment. The present study investigated the protective effects of crocin administration, exercise, and crocin-accompanied exercise on neuronal excitability and long-term potentiation (LTP) at the CA1 of hippocampus as well as serum corticosterone and glucose levels in rats subjected to chronic unpredictable stress (CUS).. Forty-eight male Wistar rats were randomly allocated to six groups: Control, Sham, CUS, CUS-Crocin30, CUS-Exercise, and CUS-Crocin30-Exercise. The chronic unpredictable stress and treadmill running at 20-21 m/min were applied 2 h/day and 1 h/day, respectively, for 21 days. Crocin (30 mg/kg) was daily intraperitoneally injected to the rats. Electrophysiological variables were recorded from the CA1 of hippocampus. While corticosterone and glucose levels were also measured.. CUS and CUS-Exercise significantly attenuated excitability and LTP. Compared to the CUS and CUS-Exercise treatments, CUS-Crocin30 and CUS-Crocin30-Exercise led to significant increases in slope and amplitude of field excitatory postsynaptic potential. The changes in serum corticosterone and glucose levels nearly matched the electrophysiological data.. CUS was found to be a highly destructive stress as it failed to allow exercises to edify the CUS-induced memory deficit. This is while crocin (as a herbal drug) was found more effective than exercise (as a daily routine) in remedying the CUS-induced memory deficit. Also, although the treatment with crocin-accompanied exercise did help recovery from the CUS-induced memory deficit, the interaction of crocin administration and exercise had no synergic effects; the protective effect observed was due to crocin administration rather than the exercise.

Topics: Animals; Blood Glucose; CA1 Region, Hippocampal; Carotenoids; Corticosterone; Disease Models, Animal; Long-Term Potentiation; Male; Memory Disorders; Physical Conditioning, Animal; Random Allocation; Rats; Rats, Wistar; Stress, Psychological

Although the memory- improving effect of crocin has been suggested by previous evidences, the association between this effect and hippocampal acetylcholine (Ach) level and apoptosis is not well investigated. This study aimed to determine the protective effects of crocin on memory, hippocampal Ach level, and apoptosis in a rat model of cerebral ischemia. Male Wistar rats were divided into sham group received saline, and other 3 groups underwent 4-vessel occlusion brain ischemia (4VOI), received oral administration of either saline or crocin in doses of 30 mg/day and 60 mg/day for 7 days. Outcomes were memory, determined by radial eight-arm maze (RAM) task and Morris water maze (MWM) test, Ach release in the dorsal hippocampus (evaluated by microdialysis-HPLC) and apoptosis (investigated by TUNEL assay). 4VOI impaired memory reduced dorsal hippocampus Ach level, and induced apoptosis. Crocin, significantly improved the memory (F = 343.20; P < 0.001 for RAM error choices and F = 182.5; P < 0.0001 for MWM), increased Ach level (F = 115.1; P < 0.001) and prevented hippocampal neuronal apoptosis (W = 183.50; P < 0.001) as compared statistically by ANOVA test. Crocin can be suggested as a promising therapy for ischemic cerebrovascular accidents by its memory preserving, Ach-increasing, and neuroprotective effects.

Topics: Acetylcholine; Animals; Apoptosis; Brain Ischemia; Carotenoids; Hippocampus; Male; Maze Learning; Memory; Memory Disorders; Neurons; Neuroprotective Agents; Rats; Rats, Wistar

Organophosphorus compounds are widely used in agriculture. Epidemiological studies propose that pesticide exposure is a risk factor for Alzheimer's disease (AD), but the mechanisms are unclear. Here, we investigated the impact of malathion exposure on the cognitive ability and the underlying mechanisms in rats. Moreover, we studied whether crocin reduced malathion-induced cognitive and memory loss in rats. Malathion (100 mg/kg) and crocin (10, 20 and 40 m/kg) were administered into the rats once a day for 14 days via i.p. Also vitamin E was used as positive control. Malathion exhibited spatial memory deficits as assessed by Morris water maze (MWM). Malathion increased the latency to reach the platform and decreased time spent and swimming distance of animals in target quadrant in probe trial. These effects were protected by crocin. Malathion exposure induced spatial learning and memory deficits with a simultaneous decrease of PSD93 and TAU hyperphosphorylation at multiple AD-related phosphorylation sites with activation of glycogen synthase kinase-3β (GSK-3β) and inhibition of protein phosphatase-2A (PP2A). Additionally, the elevation of malondialdehyde (MDA), TNF α and IL-6 levels, amelioration of reduced glutathione (GSH) in the hippocampus and reduction of plasma acetylcholinesterase activity were observed upon administration of the malathion. Also, malathion-induced apoptosis in the hippocampus. Crocin or vitamin E improved memory damages and antagonized the effects of malathion. According to the data of this study, crocin mitigated malathion-induced neurological alterations and cognitive impairment by reducing oxidative stress and inflammation, inhibiting TAU protein hyperphosphorylation and antiapoptotic effects.

Topics: Animals; Apoptosis; Carotenoids; Cholinesterase Inhibitors; Gene Expression; Glutathione; Hippocampus; Interleukin-6; Lipid Peroxidation; Malathion; Male; Memory Disorders; Phosphorylation; Rats; Rats, Wistar; tau Proteins; Tumor Necrosis Factor-alpha

The motor symptoms of Parkinson's disease (PD) are preceded by non-motorized symptoms including memory deficits. Treatment with dopamine replacement medications, such as L-DOPA only control motor symptoms and does not meet the clinical challenges of the disease, such as dyskinesia, non-motor symptoms, and neuroprotection. The purpose of the current study was to examine the neuroprotective potential of crocin and physical exercise in an animal model of PD. Male Wistar rats ran on a horizontal treadmill and/or pretreated with crocin at a dose of 100 mg/kg. Then, 16 μg of the neurotoxin 6-hydroxydopamine (6-OHDA) was microinjected into left medial forebrain bundle. Crocin treatment and/or exercise continued for 6 more weeks. Spatial and aversive memories, rotational behaviour, inflammatory and oxidative stress parameters were assessed at the end of week 6 post surgery. The results showed that pretreatment with crocin alone and in combination with exercise decreased the total number of rotaions as compared with 6-OHDA-lesioned group. Furthermore, treatment of parkinsonian rats with crocin along with exercise training improved aversive and spatial memories. Biochemical analysis showed that crocin and exercise (alone and in combination) reduced tumor necrosis factor- (TNF) α levels in the striatum. Moreover, treatment with crocin at a dose of 100 mg/kg decreased the lipid peroxidation levels in the hippocampus, while exercise training increased the total thiol concentration. In conclusion, our findings indicated that pretreatment with crocin along with treadmill exercise ameliorated motor and memory deficits induced by 6-OHDA, which is considered to be due to their antioxidant and anti-inflammatory activities. The results suggest that combined therapy with crocin and exercise may be protective for motor and memory deficits in PD patients.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Carotenoids; Disease Models, Animal; Dopamine Agents; Male; Memory Disorders; Motor Activity; Oxidative Stress; Physical Conditioning, Animal; Rats, Wistar

Extracellular beta-amyloid (Aβ) accumulation and deposition is the main factor, which causes synaptic loss and eventually cells death in Alzheimer's disease (AD). Memory loss and long-term potentiation (LTP) dysfunction in the hippocampus are involved in the AD. The involvement of crocin, as the main and active constituent of saffron extract in learning and memory processes, has been proposed. Here we investigated the probable therapeutic effect of crocin on memory, LTP, and neuronal apoptosis using in vivo Aβ models of the AD. The Aβ peptide (1-42) was bilaterally administered into the frontal-cortex using stereotaxic apparatus. Five hours after surgery, rats were given intraperitoneal crocin (30 mg/kg) daily, which repeated for 12 days. Barnes maze results showed that administration of crocin significantly improves spatial memory indicators such as latency time to achieving the target hole and the number of errors when compared to Aβ-group. Passive avoidance test revealed that crocin significantly increased the step-through-latency compared to Aβ-treated alone. These learning deficits in Aβ-treated animals correlated with a reduction of LTP in hippocampal CA1 synapses in freely moving rats, which crocin improved population spike amplitude and mean field excitatory postsynaptic potentials (fEPSP) slope reduction induced by Aβ. Neuronal apoptosis was detected by TUNEL assay and the expression levels of c-Fos proteins were examined by Western blotting. Crocin significantly reduced the number of TUNEL-positive cells in the CA1 region and decreased c-Fos in the hippocampus compared to Aβ-group. In vivo Aβ treatment altered significantly the electrophysiological properties of CA1 neurons and crocin further confirmed a neuroprotective action against Aβ toxicity.

Topics: Amyloid beta-Peptides; Animals; Antioxidants; Avoidance Learning; CA1 Region, Hippocampal; Carotenoids; Disease Models, Animal; Electric Stimulation; Electrodes, Implanted; In Situ Nick-End Labeling; Long-Term Potentiation; Male; Maze Learning; Memory Disorders; Neurons; Peptide Fragments; Proto-Oncogene Proteins c-fos; Rats; Rats, Wistar; Time Factors; Wakefulness

Tramadol, a frequently used pain reliever drug, present neurotoxic effects associated to cognitive dysfunction. Moreover, crocin has been reported to have neuroprotective effects. The aim of this study was to assess crocin's capacity to protect learning, and memory abilities on tramadol-treated rats. A total of 35 rats were divided into five groups: Control, Saline, tramadol (50 mg/kg), tramadol + crocin(30 mg/kg), crocin groups and treated orally for 28 consecutive days. Morris water maze (MWM) and passive avoidance (PA) tests were done, followed by dissection of the rat's brains for toluidine blue and TUNEL staining. In MWM test, tramadol group spent lower time and traveled shorter distance in the target quadrant (Q1) (P < 0.05). On the other side, the traveled distance in tramadol-crocin group was higher than tramadol (P < 0.05). In PA test, both the delay for entering the dark, and the total time spent in the light compartment decreased in tramadol comparing to the control group (P < 0.05), while it increased in tramadol-crocin compared with the tramadol group (P < 0.05). In tramadol-treated animals, the dark neurons (DNs) and apoptotic cells in CA1, CA3 and DG increased (P < 0.05), while concurrent intake of crocin decreased the number of DNs and apoptotic cells in these areas (P < 0.05). Crocin was able to improve learning and memory of tramadol-treated rats and also decreased DNs and apoptotic cells in the hippocampus. Considering these results, the potential capacity of crocin for decreasing side effects of tramadol on the nervous system is suggested.

Topics: Animals; Antioxidants; Apoptosis; Carotenoids; Hippocampus; Male; Maze Learning; Memory; Memory Disorders; Neurons; Neuroprotective Agents; Plant Extracts; Rats, Wistar; Tramadol

The purpose of the current study was to examine the influence of crocin on improving spatial memory deficits and cerebral oxidative damage in streptozotocin-induced diabetic rats. Crocin was administered intraperitoneally daily at doses of 15, 30 and 60mg/kg for 6 weeks. Spatial memory performance was measured in rats by the Morris water maze paradigm. Lipid peroxidation and total thiol levels as parameters of oxidative stress were assessed in the cerebral cortex at the end of week 6. Diabetic rats showed spatial learning and memory deficits in the Morris water maze which was accompanied by increased lipid peroxidation levels in the cerebral cortex. By contrast, chronic treatment with crocin (15, 30 and 60mg/kg, ip, 6 weeks) improved cognitive performance and lowered hyperglycaemia and oxidative stress in diabetic rats. In conclusion, the results suggest that beneficial effects of crocin on streptozotocin-induced memory dysfunction may be attributed to its antidiabetic and antioxidant activity, which could find clinical use in treating cognitive dysfunction in diabetics.

Topics: Animals; Blood Glucose; Carotenoids; Cerebral Cortex; Diabetes Mellitus, Experimental; Free Radical Scavengers; Lipid Peroxidation; Male; Malondialdehyde; Memory Disorders; Oxidative Stress; Rats; Rats, Wistar; Spatial Learning; Spatial Memory; Sulfhydryl Compounds; Treatment Outcome

The purpose of the present study was to investigate the effect of crocin on brain oxidative damage and memory deficits in a 6-hydroxydopamine (6-OHDA) model of Parkinson's disease. Male Wistar rats were subjected to unilateral injection of 6-OHDA (16 µg) into the medial forebrain bundle and treated with crocin (30 and 60 mg/kg) for six weeks. The rats were tested for memory performance at six weeks after 6-OHDA infusion, and then were killed for the estimation of biochemical parameters. The increase in thiobarbituric acid reactive substances (TBARS) and nitrite levels in the hippocampus were observed in the 6-OHDA lesioned rats, which was accompanied by memory deficits in a passive avoidance test at the end of week 6. Moreover, treatment with crocin decreased TBARS and nitrite levels in the hippocampus, and improved aversive memory. The present study conclusively demonstrated that crocin acts as an antioxidant and anti-inflammatory agent in the hippocampus of parkinsonian rats and could improve aversive memory through its properties.

Topics: Animals; Antioxidants; Carotenoids; Cerebral Cortex; Disease Models, Animal; Glutathione Peroxidase; Lipid Peroxidation; Male; Memory; Memory Disorders; Nitrites; Oxidative Stress; Oxidopamine; Parkinson Disease; Random Allocation; Rats, Wistar; Sulfhydryl Compounds; Thiobarbituric Acid Reactive Substances

Crocin, as a carotenoid, is one of the main and active constituents of saffron stigmas (Crocus sativus L.) that is widely used in folk medicine. Several studies have pointed out the potent antioxidant and neuroprotective properties of crocin which may have therapeutic values for management of neurodegenerative disorders such as Alzheimer's disease. Alzheimer's disease is the most common form of dementia among the elderly and is characterized by massive neuronal loss and progressive cognitive impairment. Beta amyloid hypothesis is the main theoretical research framework for Alzheimer's disease which states that extracellular aggregation of beta amyloid results in synaptic loss and eventually cell apoptosis. Recent findings suggest that autophagy and apoptosis are extensively involved in Alzheimer's disease. In order to investigate therapeutic values of crocin, we examined the effect of crocin on memory, cell apoptosis, and autophagy using in vivo models of Alzheimer's disease. We also compared the effect of crocin administration on spatial memory with nicotine as positive control. Morris water maze results show that intra-peritoneal and intra-hippocampal administration of crocin significantly improve spatial memory indicators such as escape latency, traveled distance and time spent in target quadrant when compared to beta amyloid injection. Furthermore, we measured certain biomarkers of cell autophagy and apoptosis using Western blot analysis. Our results reveal that crocin administration does not cause any significant alteration in Beclin-1 and ratio of LC3-II/LC3-I compared to the group received beta amyloid by hippocampal injection. However, in contrast to autophagy, crocin administration significantly decreases Bax/Bcl-2 ratio and cleaved Caspase-3 level. This demonstrates that crocin inhibits beta amyloid induced apoptosis, which is possibly associated with its antioxidant properties. Our results further confirm the neuroprotective properties of crocin as a potential pharmaceutical agent for management of Alzheimer's disease.

Topics: Amyloid beta-Peptides; Animals; Apoptosis; Apoptosis Regulatory Proteins; Autophagy; Behavior, Animal; Carotenoids; Hippocampus; Memory Disorders; Microinjections; Neuroprotective Agents; Nicotine; Peptide Fragments

Experimental evidence indicates that the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine impairs cognition and can mimic certain aspects of positive and negative symptoms of schizophrenia in rodents. Crocins are among the active components of the plant Crocus sativus L. and were found to be effective in different models of psychiatric disorders including anxiety and depression.. The present study was designed to investigate the ability of crocins to counteract schizophrenia-like behavioural deficits produced by ketamine in rats.. Crocin's ability to counteract hypermotility, stereotypies and ataxia induced by ketamine was evaluated in a motor activity cage. The ability of crocins to reverse ketamine-induced memory deficits was assessed using the novel object recognition task (NORT). The social interaction test was used in order to examine the effects of crocins on ketamine-induced social withdrawal.. Crocins (50 but not 30 mg/kg, i.p.) attenuated ketamine (25 mg/kg, i.p.)-induced hypermotility, stereotypies and ataxia. In a subsequent study, post-training administration of crocins (15 and 30 mg/kg, i.p.) reversed ketamine (3 mg/kg, i.p.)-induced performance deficits in the NORT. Finally, crocins (50 but not 30 mg/kg, i.p.) counteracted the ketamine (8 mg/kg, i.p.)-induced social isolation in the social interaction test.. Our findings show that crocins attenuated schizophrenia-like behavioural deficits induced by the non-competitive NMDA receptor antagonist ketamine in rats.

Topics: Animals; Antipsychotic Agents; Ataxia; Carotenoids; Ketamine; Male; Memory Disorders; Motor Activity; Neuropsychological Tests; Rats; Rats, Wistar; Recognition, Psychology; Social Behavior; Stereotypic Movement Disorder; Time Factors

Intracerebroventricular (ICV) streptozotocin (STZ) has been shown to cause cognitive impairment, associated with free radical generation. In this study, we evaluated the effects of crocin on cognitive performance in ICV STZ-lesioned rats (3 mg/kg bilaterally, on day 1 and 3). Crocin (100 mg/kg, p.o.) was administered for 21 consecutive days, starting 1h prior to the first dose of STZ. Cognitive performance was assessed using Morris water maze task while the parameters of oxidative stress assessed, were malondialdehyde (MDA) and total thiol levels besides glutathione peroxidase (GPx) activity. STZ-lesioned rats showed a severe deficit in memory associated with elevated MDA levels, reduced GPx activity and total thiol content. Crocin treatment improved cognitive performance and resulted in a significant reduction in MDA levels and elevation in total thiol content and GPx activity. This study demonstrates that crocin may have beneficial effects in the treatment of neurodegenerative disorders such as Alzheimer's disease.

Topics: Alzheimer Disease; Animals; Antioxidants; Brain; Carotenoids; Cognition; Cognition Disorders; Crocus; Free Radicals; Glutathione Peroxidase; Male; Malondialdehyde; Maze Learning; Memory Disorders; Oxidative Stress; Phytotherapy; Plant Extracts; Rats; Rats, Wistar; Streptozocin; Sulfhydryl Compounds

Cerebral ischemia produces brain damage and related behavioral deficits such as memory. In this study, a rat model of chronic cerebral hypoperfusion was used to determine whether saffron extract and crocin, which are potent antioxidants and free radical scavengers, can reduce vascular cognitive impairment. Male adult Wistar rats were administered different doses of an aqueous solution of crocin or hydroalcohol extract of saffron intraperitoneally (i.p.) 5 days after permanent occlusion of the common carotid arteries. Spatial learning and memory were assessed in training trials, 7-11 days after common carotid artery ligation using the Morris water maze. The results showed that the escape latency time was significantly reduced from 24.64 s in the control group to 8.77 and 10.47 s by crocin (25 mg/kg) and saffron extract (250 mg/kg). The traveled distance to find the platform was also changed from 772 cm in the control group to 251 and 294 cm in the crocin (25 mg/kg) and saffron extract (250 mg/kg) groups. The percentages of time spent in the target quadrant, in comparison with the control group (24.16%), increased to 34.25% in the crocin (25 mg/kg) and 34.85% in the saffron extract (250 mg/kg) group. This study suggests that saffron extract and crocin improve spatial cognitive abilities following chronic cerebral hypoperfusion and that these effects may be related to the antioxidant effects of these compounds.

Topics: Animals; Antioxidants; Carotenoids; Carotid Artery, Common; Coronary Occlusion; Crocus; Male; Memory; Memory Disorders; Models, Animal; Phytotherapy; Plant Extracts; Rats; Rats, Wistar; Recognition, Psychology; Spatial Behavior; Time Factors

Optimized-SopungSunkiwon (OSS) is a multi-herbal formula that contains six medicinal herbs from SopungSunkiwon, a traditional medicine used for neurodegenerative disorders. In this study, we investigated the anti-amnesic effects of OSS in a dementia model. Acetylcholinesterase (AChE) inhibition assay was performed to investigate the cholinergic antagonistic effect of OSS. In addition, a step-through passive-avoidance test was performed with scopolamine-induced memory impairment in mice, and immunohistochemistry was analyzed to investigate synaptic formation with synaptic proteins. OSS inhibited AChE activity, resulting in significant improvement of memory functions. In the passive-avoidance test, the latency time of OSS-treated mice was significantly longer than that of either the control or scopolamine-treated group. In the immunohistochemical analysis, synaptic proteins such as synaptophysin and PSD-95 were significantly increased in OSS-treated mice. These results demonstrate that OSS may affect impairment and enhancement of memory and increase synaptophysin and PSD-95 facilitating acetylcholine release and synaptic growth.

Topics: Acetylcholinesterase; Animals; Anthraquinones; Avoidance Learning; Brain; Carotenoids; Chromatography, High Pressure Liquid; Immunohistochemistry; Iridoids; Male; Maze Learning; Medicine, Korean Traditional; Memory; Memory Disorders; Mice; Mice, Inbred ICR; Neuroprotective Agents; Phytotherapy; Plant Extracts; Plants, Medicinal; Senna Extract; Sennosides