rosmarinic-acid and Memory-Disorders

The purpose of this study was to investigate the effects of supplementation with a spearmint (Mentha spicata L.) extract, high in polyphenols including rosmarinic acid, on cognitive performance, sleep, and mood in individuals with age-associated memory impairment (AAMI).. Subjects with AAMI (N = 90; 67% female; age = 59.4 ± 0.6 years) were randomly assigned (n = 30/group) to consume 900, 600, or 0 mg/day (two capsules, once daily) spearmint extract for 90 days, in this double-blind, placebo-controlled trial. Assessments were completed for cognition (days 0, 45, and 90), sleep (days 0 and 90), and mood (days 0 and 90) by using the Cognitive Drug Research (CDR) System. Quality of working memory and spatial working memory accuracy improved after supplementation with 900 mg/day spearmint extract by 15% (p = 0.0469) and 9% (p = 0.0456), respectively, versus placebo. Subjects consuming 900 mg/day spearmint extract reported improvement in their ability to fall asleep, relative to subjects consuming placebo (p = 0.0046). Overall treatment effects were evident for vigor-activity (p = 0.0399), total mood disturbance (p = 0.0374), and alertness and behavior following wakefulness (p = 0.0415), with trends observed for improvements after spearmint supplementation relative to placebo.. These results suggest that the distinct spearmint extract may be a beneficial nutritional intervention for cognitive health in older subjects with AAMI.

Topics: Cinnamates; Cognition; Depsides; Female; Humans; Male; Memory Disorders; Memory, Short-Term; Mentha spicata; Middle Aged; Plant Extracts; Polyphenols; Rosmarinic Acid; Sleep

Memory impairment is one of the disabling manifestations of multiple sclerosis (MS) possibly present from the early stages of the disease and for which there is no specific treatment. Hippocampal synaptic dysfunction and dendritic loss, associated with microglial activation, can underlie memory deficits, yet the molecular mechanisms driving such hippocampal neurodegeneration need to be elucidated. In early-stage experimental autoimmune encephalomyelitis (EAE) female mice, we assessed the expression level of molecules involved in microglia-neuron interactions within the dentate gyrus and found overexpression of genes of the complement pathway. Compared to sham immunized mice, the central element of the complement cascade, C3, showed the strongest and 10-fold upregulation, while there was no increase of downstream factors such as the terminal component C5. The combination of in situ hybridization with immunofluorescence showed that C3 transcripts were essentially produced by activated microglia. Pharmacological inhibition of C3 activity, by daily administration of rosmarinic acid, was sufficient to prevent early dendritic loss, microglia-mediated phagocytosis of synapses in the dentate gyrus, and memory impairment in EAE mice, while morphological markers of microglial activation were still observed. In line, when EAE was induced in C3 deficient mice (C3KO), dendrites and spines of the dentate gyrus as well as memory abilities were preserved. Altogether, these data highlight the central role of microglial C3 in early hippocampal neurodegeneration and memory impairment in EAE and, therefore, pave the way toward new neuroprotective strategies in MS to prevent cognitive deficit using complement inhibitors.

Topics: Animals; Cinnamates; Complement C3; Complement C3-C5 Convertases; Dendrites; Depsides; Encephalomyelitis, Autoimmune, Experimental; Hippocampus; Memory Disorders; Mice; Mice, Knockout; Microglia; Molybdoferredoxin; Multiple Sclerosis; Nerve Degeneration; Phagocytosis; Rosmarinic Acid; Synapses

Oxidative stress plays a pivotal part in the manifestation of neuroinflammation, which further leads to neurodegenerative diseases like Alzheimer's disease (AD). Systemic administration of lipopolysaccharide (LPS) induces neuroinflammation resulting in memory impairment (MI) and cognitive decline. In this study, we evaluated whether prophylactic administration of Rosmarinic acid (RA), a naturally occurring compound, exerts a neuroprotective effect in LPS-induced MI and cognitive decline. Herein, Swiss albino mice were pre-treated with RA (0.5 mg/kg and 1 mg/kg i.p.) for 28 days and were intermittently exposed to LPS (0.25 mg/kg i.p.) for 7 days. LPS caused poor memory retention and increased cognitive decline in Morris water maze (MWM) and Y maze paradigms respectively. Additionally, LPS increased oxidative stress which was denoted by a decrease in superoxide dismutase (SOD) activity, decrease in reduced glutathione (GSH) levels, and increased lipid peroxidation in the brain. Imbalance in the cholinergic system was analyzed by measuring the acetylcholinesterase (AChE) activity. Pre-treatment with RA improved memory and behavioral disturbances by alleviating oxidative stress and AChE activity. LPS augmented levels of tumor necrosis factor (TNF-α), interleukin (IL)-6, caspase-3, and c-Jun. Pre-treatment with RA revitalized the elevated levels of proinflammatory cytokines and apoptotic proteins. In conclusion, this study showcases the amelioration of MI by RA in LPS-challenged memory and cognitive decline, which could be credited to its anti-oxidant effect, inhibitory effect on both proinflammatory cytokines and apoptotic regulators, and reduction in AChE activity.

Topics: Animals; Brain; Cinnamates; Cytokines; Depsides; Hippocampus; Inflammation; Lipopolysaccharides; Maze Learning; Memory; Memory Disorders; Mice; Neuroprotective Agents; Oxidative Stress; Rosmarinic Acid

In the present study, we examined whether rosmarinic acid (RA) reverses amyloid β (Aβ) induced reductions in antioxidant defense, lipid peroxidation, cholinergic damage as well as the central auditory deficits. For this purpose, Wistar rats were randomly divided into four groups; Sham(S), Sham + RA (SR), Aβ42 peptide (Aβ) and Aβ42 peptide + RA (AβR) groups. Rat model of Alzheimer was established by bilateral injection of Aβ42 peptide (2,2 nmol/10 μl) into the lateral ventricles. RA (50 mg/kg, daily) was administered orally by gavage for 14 days after intracerebroventricular injection. At the end of the experimental period, we recorded the auditory event related potentials (AERPs) and mismatch negativity (MMN) response to assess auditory functions followed by histological and biochemical analysis. Aβ42 injection led to a significant increase in the levels of thiobarbituric acid reactive substances (TBARS) and 4-Hydroxy-2-nonenal (4-HNE) but decreased the activity of antioxidant enzymes (SOD, CAT, GSH-Px) and glutathione levels. Moreover, Aβ42 injection resulted in a reduction in the acetylcholine content and acetylcholine esterase activity. RA treatment prevented the observed alterations in the AβR group. Furthermore, RA attenuated the increased Aβ staining and astrocyte activation. We also found that Aβ42 injection decreased the MMN response and theta power/coherence of AERPs, suggesting an impairing effect on auditory discrimination and echoic memory processes. RA treatment reversed the Aβ42 related alterations in AERP parameters. In conclusion, our study demonstrates that RA prevented Aβ-induced antioxidant-oxidant imbalance and cholinergic damage, which may contribute to the improvement of neural network dynamics of auditory processes in this rat model.

Topics: Amyloid beta-Peptides; Animals; Antioxidants; Cholinergic Neurons; Cinnamates; Depsides; Evoked Potentials, Auditory; Male; Memory Disorders; Neuroprotective Agents; Oxidative Stress; Peptide Fragments; Rats; Rats, Wistar; Rosmarinic Acid

Ethanol consumption induces neurological disorders including cognitive dysfunction. Oxidative damage is considered a likely cause of cognitive deficits. We aimed to investigate the effects of rosmarinic acid (RA) in different doses for 30 days on chronic ethanol-induced cognitive dysfunction using the passive avoidance learning (PAL) and memory task in comparison with donepezil, a reference drug. We also evaluated the levels of superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation in hippocampus as possible mechanisms.. Memory impairment was induced by 15% w/v ethanol (2 g/kg, i.g.) administration for 30 days. RA (8, 16, and 32 mg/kg, i.g.) or donepezil (2 mg/kg, i.g.) was administered 30 minutes before ethanol. The acquisition trial was done 1 hour after the last administration of RA and donepezil. At the end, animals were weighed and hippocami were isolated for analyzing of oxidant/antioxidant markers.. Ethanol caused cognition deficits in the PAL and memory task. While RA 16 and 32 mg/kg improved cognition in control rats, it prevented learning and memory deficits of alcoholic groups. RA 8 mg/kg did not influence cognitive function in both control and alcoholic rats. RA 32 mg/kg had comparable effects with donepezil in prevention of acquisition and retention memory impairment. The higher doses of RA not only prevented increased lipid peroxidation and nitrite content but also decreased SOD, CAT, GSH, and FRAP levels in alcoholic groups and exerted antioxidant effects in non-alcoholic rats.. We showed that RA administration dose-dependently prevented cognitive impairment induced by chronic ethanol in PAL and memory and disturbed oxidant/antioxidant status as a possible mechanism. The antioxidant, anticholinesterase, and neuroprotective properties of RA may be involved in the observed effects. Therefore, RA represents a potential therapeutic option against chronic ethanol-induced amnesia which deserves consideration and further examination.

Topics: Alcohol-Induced Disorders, Nervous System; Animals; Antioxidants; Avoidance Learning; Behavior, Animal; Biomarkers; Cholinesterase Inhibitors; Cinnamates; Depsides; Dietary Supplements; Donepezil; Exploratory Behavior; Hippocampus; Indans; Learning Disabilities; Lipid Peroxidation; Male; Memory Disorders; Neurons; Neuroprotective Agents; Nootropic Agents; Oxidative Stress; Piperidines; Random Allocation; Rats, Wistar; Rosmarinic Acid

Prunella vulgaris L. is as a major plant in the Chinese traditional functional beverage Guangdong herbal tea for the treatment of fevers, diarrhea, and sore mouth. In this study, ethyl acetate parts of aqueous extracts from P. vulgaris L. (EtOAc-APV) were found to demonstrate potent acetylcholinesterase (AChE) inhibition in vitro. Therefore, this study was designed to further investigate the effects of EtOAc-APV on scopolamine (SCOP)-induced aging rats. Male Wistar rats were randomly divided into four groups (n = 12) and given orally by gavage EtOAc-APV (100 mg/kg) for 3 weeks. SCOP (1 mg/kg, ip) was administered to rats 30 min before starting behavioral tests consecutively for 3 days. EtOAc-APV could attenuate SCOP-induced brain senescence in rats by improving behavioral performance and decreasing brain cell damage, which was associated with a notable reduction in AChE activity and MDA level, as well as an increase in SOD and GPx activities. Additionally, EtOAc-APV administration could reduce the expression of NF-κB and GFAP, which showed an anti-neuroinflammatory effect on the SCOP-treated rat. Overall, the current study highlights P. vulgaris L. as an antidementia dietary supplement.

Topics: Animals; Apoptosis; Caffeic Acids; Cholinesterase Inhibitors; Cinnamates; Depsides; Flavonoids; Hippocampus; Male; Memory Disorders; Neuroprotective Agents; NF-kappa B; Plant Extracts; Plants, Medicinal; Prunella; Rats, Wistar; Rosmarinic Acid; Scopolamine

Polyphenols have neuroprotective effects after brain ischemia. It has been demonstrated that rosmarinic acid (RA), a natural phenolic compound, possesses antioxidant and anti-inflammatory properties. To evaluate the effectiveness of RA against memory deficits induced by permanent middle cerebral artery occlusion (pMCAO) mice were treated with RA (0.1, 1, and 20mg/kg/day, i.p. before ischemia and during 5 days). Animals were evaluated for locomotor activity and working memory 72 h after pMCAO, and spatial and recognition memories 96 h after pMCAO. In addition, in another set of experiments brain infarction, neurological deficit score and myeloperoxidase (MPO) activity were evaluates 24h after the pMCAO. Finally, immunohistochemistry, and western blot, and ELISA assay were used to analyze glial fibrillary acidic protein (GFAP), and synaptophysin (SYP) expression, and BDNF level, respectively. The working, spatial, and recognition memory deficits were significantly improved with RA treatment (20mg/kg). RA reduced infarct size and neurological deficits caused by acute ischemia. The mechanism for RA neuroprotection involved, neuronal loss suppression, and increase of synaptophysin expression, and increase of BDNF. Furthermore, the increase of MPO activity and GFAP immunireactivity were prevented in MCAO group treated with RA. These results suggest that RA exerts memory protective effects probably due to synaptogenic activity and anti-inflammatory action.

Topics: Animals; Astrocytes; Brain; Brain Ischemia; Brain-Derived Neurotrophic Factor; Cinnamates; Depsides; Disease Models, Animal; Dose-Response Relationship, Drug; Gliosis; Infarction, Middle Cerebral Artery; Male; Memory Disorders; Memory, Short-Term; Mice; Motor Activity; Neuroprotective Agents; Peroxidase; Recognition, Psychology; Rosmarinic Acid; Spatial Memory; Synapses

Learning and memory impairment occurs in diabetes. Salvia officinalis L. (SO) has been used in Iranian traditional medicine as a remedy against diabetes. We hypothesized that chronic administration of SO (400, 600 and 800mg/kg, p.o.) and its principal constituent, rosmarinic acid, would affect on passive avoidance learning (PAL) and memory in streptozocin-induced diabetic and non-diabetic rats. We also explored hypoglycemic and antioxidant activities of SO as the possible mechanisms. Treatments were begun at the onset of hyperglycemia. PAL was assessed 30days later. Retention test was done 24h after training. At the end, animals were weighed and blood samples were drawn for further analyzing of glucose and oxidant/antioxidant markers. Diabetes induced deficits in acquisition and retrieval processes. SO (600 and 800mg/kg) and rosmarinic acid reversed learning and memory deficits induced by diabetes and improved cognition of healthy rats. While the dose of 400mg/kg had no effect, the higher doses and rosmarinic acid inhibited hyperglycemia and lipid peroxidation as well as enhanced the activity of antioxidant enzymes superoxide dismutase and catalase. SO prevented diabetes-induced acquisition and memory deficits through inhibiting hyperglycemia, lipid peroxidation as well as enhancing antioxidant defense systems. Therefore, SO and its principal constituent rosmarinic acid represent a potential therapeutic option against diabetic memory impairment which deserves consideration and further examination.

Topics: Animals; Antioxidants; Avoidance Learning; Cinnamates; Depsides; Diabetes Mellitus, Experimental; Hypoglycemic Agents; Learning Disabilities; Male; Memory; Memory Disorders; Oxidative Stress; Plant Extracts; Rats, Wistar; Retention, Psychology; Rosmarinic Acid; Salvia officinalis

Rosmarinic acid (RA) is a natural phenol that exerts different biological activities, such as antioxidant activity and neuroprotective effects. In this study, we hypothesized that administration of RA (8, 16, and 32 mg/kg, p.o.) for 7 days would effect on scopolamine-induced cognitive dysfunction as an extensively used model of cognitive impairment. The rats were divided into 10 groups. The acquisition trial was done 1h after the last administration of RA. Animals were divided into control, RA (8, 16, and 32 mg/kg) and donepezil (2 mg/kg) treated controls, scopolamine, RA (8, 16, and 32 mg/kg), and donepezil (2 mg/kg) treated scopolamine groups. Memory impairment was induced by scopolamine treatment (1 mg/kg, i.p.) 30 min after the administration of RA, donepezil, or saline. Scopolamine administration caused cognition deficits in the PAL and memory paradigm. While orally RA administration (16 and 32 mg/kg) improved learning and memory in control rats, it reversed learning and memory deficits of scopolamine received groups. Administration of RA at the dose of 8 mg/kg did not alter cognitive function in control and scopolamine treated groups. The combination of anticholinesterase, neuroprotective, and antioxidant properties of RA may all be responsible for the observed effects. These results indicate the beneficial effects of subchronic RA administration in passive avoidance learning and memory in control rats as well as in a pharmacological model of cholinergic deficit which continue to expand the knowledge base in creating new treatment strategies for cognition deficits and dementia. Of course, further studies are warranted for clinical use of RA in the management of demented subjects.

Topics: Animals; Avoidance Learning; Cholinergic Antagonists; Cinnamates; Depsides; Donepezil; Indans; Male; Memory; Memory Disorders; Neuroprotective Agents; Piperidines; Rats, Wistar; Reaction Time; Rosmarinic Acid; Scopolamine

Peroxynitrite (ONOO(-))-mediated damage is regarded to be responsible for the cognitive dysfunction induced by amyloid beta protein (Abeta) in Alzheimer's disease (AD). In the present study, we examined the protective effects of rosmarinic acid (RA), a natural scavenger of ONOO(-), on the memory impairment in a mouse model induced by acute i.c.v. injection of Abeta(25-35). Mice daily received i.p. several doses of RA after the injection of Abeta(25-35). RA prevented the memory impairments induced by Abeta(25-35) in the Y maze test and novel object recognition task. RA, at the effective lowest dose (0.25mg/kg), prevented Abeta(25-35)-induced nitration of proteins, an indirect indicator of ONOO(-) damage, in the hippocampus. At this dose, RA also prevented nitration of proteins and impairment of recognition memory induced by ONOO(-)-i.c.v.-injection. Co-injection of the non-memory-impairing dose of ONOO(-) with Abeta(25-35) blocked the protective effects of RA (0.25mg/kg). These results demonstrated that the memory protective effects of RA in the neurotoxicity of Abeta(25-35) is due to its scavenging of ONOO(-), and that daily consumption of RA may protect against memory impairments observed in AD.

Topics: Amyloid beta-Peptides; Analysis of Variance; Animals; Behavior, Animal; Blotting, Western; Cinnamates; Depsides; Dose-Response Relationship, Drug; Drug Interactions; Male; Maze Learning; Memory Disorders; Mice; Mice, Inbred ICR; Neuroprotective Agents; Neuropsychological Tests; Peroxynitrous Acid; Rosmarinic Acid