alpha-asarone and Alzheimer-Disease

Alzheimer's disease (AD) is a slowly progressive neurodegenerative disease which cannot be cured at present. The aim of this study was to assess whether the combined application of β-asarone and tenuigenin could improve the efficacy of memantine in treating moderate-to-severe AD.. One hundred and fifty-two patients with moderate-to-severe AD were recruited and assigned to two groups. Patients in the experiment group received β-asarone 10 mg/d, tenuigenin 10 mg/d, and memantine 5-20 mg/d. Patients in the control group only received memantine 5-20 mg/d. The Mini Mental State Examination (MMSE), Clinical Dementia Rating Scale (CDR), and Activities of Daily Living (ADL) were used to assess the therapeutic effects. The drug-related adverse events were used to assess the safety and acceptability. Treatment was continued for 12 weeks.. After 12 weeks of treatment, the average MMSE scores, ADL scores, and CDR scores in the two groups were significantly improved. But, compared to the control group, the experimental group had a significantly higher average MMSE score (. These results demonstrated that the combined application of β-asarone and tenuigenin could improve the efficacy of memantine in treating moderate-to-severe AD. The clinical applicability of this novel method showed greater promise and should be further explored.

Topics: Activities of Daily Living; Aged; Allylbenzene Derivatives; Alzheimer Disease; Anisoles; Drug Therapy, Combination; Drugs, Chinese Herbal; Humans; Male; Memantine; Middle Aged; Psychiatric Status Rating Scales; Severity of Illness Index; Treatment Outcome

Alzheimer's disease (AD) is a neurological ailment that causes memory loss and impairments and is linked to a drop-in acetylcholine level. Acetylcholinesterase (AChE) inhibitors are used for the management of AD. In our ongoing research to search for natural AChE inhibitors from medicinal plants, we found that the Acorus calamus possesses memory-enhancing properties. α-Asarone is the major compound isolated from the Acorus calamus and it has neuroprotective action in animal models, nonetheless, its anticholinesterase activity in different brain regions was not fully understood. The purpose of this research was to determine the anti-amnesic and anti-cholinesterase activities of α-asarone against scopolamine-induced memory impairments in rats.. The anti-cholinesterase activity of α-asarone was determined using Ellman's method in different brain areas, such as the cortex, hippocampus, and striatum. In addition, the anti-amnesic effect of α-asarone was also investigated using elevated plus-maze, passive avoidance, and active avoidance tests.. The effect of α-asarone on memory impairment against scopolamine-induced (1 mg/kg body weight) amnesia was evaluated. Administration of α-asarone (15 and 30 mg/kg body weight) for 14 days to rats significantly ameliorated the scopolamine-induced memory impairment as measured in the elevated plus-maze, passive avoidance, and avoidance active tests compared to the scopolamine-treated group. In this study, we also show that α-asarone treatment significantly (p<0.05) reduced brain acetylcholinesterase activity in the cortex, hippocampus, and striatum brain regions of amnesic rats.. These results confirmed that α-asarone has anti-amnesic and anti-cholinesterase potential which may be useful for the management of AD.

Topics: Acetylcholine; Acetylcholinesterase; Allylbenzene Derivatives; Alzheimer Disease; Amnesia; Animals; Anisoles; Avoidance Learning; Body Weight; Cholinesterase Inhibitors; Maze Learning; Memory Disorders; Rats; Scopolamine

Topics: Allylbenzene Derivatives; Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Anisoles; Cognition; Disease Models, Animal; Hippocampus; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neurodegenerative Diseases; Neurons; Presenilin-1; Rats

Alzheimer's disease (AD) is a common neurodegenerative disease in the elderly population. Autophagy is a well‑known regulator of neurodegenerative diseases and β‑asarone has been discovered to have certain neuropharmacological effects. Thus, the present study aimed to analyze the potential effects of β‑asarone in AD and its possible mechanism of action in relation to autophagy. The present study investigated the effects of β‑asarone on the number of senile plaques and amyloid β(Aβ)40, Aβ42, amyloid precursor protein (APP) and Beclin‑1 mRNA levels in the hippocampus of APP/presenilin‑1 (PS1) transgenic mice. The possible mechanism of β‑asarone on autophagy‑related proteins, including Beclin‑1, light chain (LC)3A, LC3B and p62 levels, and the number of autophagosomes was also investigated. Mice were divided into a normal control group, a model group, a β‑asarone‑treated group, a 3‑MA‑treated group and a rapamycin‑treated group. Treatments were continuously administered to all mice for 30 days by intragastric administration. The mice, including those in the normal and model control groups, were given equal volumes of saline. It was demonstrated that β‑asarone treatment reduced the number of senile plaques and autophagosomes, and decreased Aβ40, Aβ42, APP and Beclin‑1 expression in the hippocampus of model mice compared with untreated model mice. β‑asarone also inhibited LC3A/B expression levels, but increased p62 expression. It was deduced that the neuroprotective effects of β‑asarone in APP/PS1 transgenic mice resulted from its inhibition of autophagy. In conclusion, the data suggested that β‑asarone should be explored further as a potential therapeutic agent in AD.

Topics: Allylbenzene Derivatives; Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Anisoles; Autophagy; Autophagy-Related Proteins; Beclin-1; Brain; Disease Models, Animal; Female; Hippocampus; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microtubule-Associated Proteins; Neurodegenerative Diseases; Peptide Fragments; Plaque, Amyloid; Presenilin-1

Alzheimer's disease (AD) is a chronic neurodegenerative disease that is characterized by the extracellular accumulation of β-amyloid (Aβ). Many studies have shown a close relationship between autophagy and the formation of Aβ. As AD develops and progresses, mitophagy diminishes insoluble Aβ, and mitochondrial dysfunction seems to be a determining factor in the pathogenesis of AD. In our previous study, we showed that β-asarone pharmacological effects in APP/PS1 transgenic mice, reducing Aβ expression. However, the specific mechanism of this effect remains unclear. In this study, AD model rats induced by intracerebroventricular injection of Aβ

Topics: Allylbenzene Derivatives; Alzheimer Disease; Amyloid beta-Peptides; Animals; Anisoles; Disease Models, Animal; Female; Hippocampus; Learning; Male; Maze Learning; Memory; Mitophagy; Neurons; Peptide Fragments; Protein Kinases; Rats; Rats, Wistar; Ubiquitin-Protein Ligases

Alzheimer's disease (AD) is a progressive, neurodegenerative brain disorder associated with loss of memory and cognitive function. Beta-amyloid (Aβ) aggregates, in particular, are known to be highly neurotoxic and lead to neurodegeneration. Therefore, blockade or reduction of Aβ aggregation is a promising therapeutic approach in AD. We have previously reported an inhibitory effect of the methanol extract of

Topics: Allylbenzene Derivatives; Alzheimer Disease; Amyloid beta-Peptides; Animals; Anisoles; Humans; Nitric Oxide; PC12 Cells; Perilla frutescens; Plant Leaves; Protein Aggregation, Pathological; Rats

Alzheimer's disease (AD) is a progressive neurodegenerative disease that has no cure at present. This study was carried out to evaluate whether the combination of β-asarone and tenuigenin could improve the efficacy of memantine as a monotherapy in the treatment of AD. Patients with AD were recruited and assigned to two groups. Patients in the control group received memantine (5-20 mg/day) and those in the experimental group received memantine (5-20 mg/day), β-asarone (20 mg/day), and tenuigenin (20 mg/day). The Mini-Mental State Examination (MMSE), Activities of Daily Living (ADL), Clinical Dementia Rating Scale (CDR) scores and drug-related side-effects were assessed. Treatment was continued for 12 weeks. In total, 93 AD patients (45 in the control group and 48 in the experimental group) were recruited. Before treatment, both the groups had similar average MMSE scores, ADL scores, and CDR scores, whereas all the average scores improved significantly after treatment. However, compared with the control group, the experimental group had a significantly higher average MMSE score (P=0.00001) and lower average ADL (P=0.00604) and CDR (P=0.00776) scores after treatment. Moreover, the two groups had similar rates of drug-related side-effects. These results indicated that the combination of β-asarone and tenuigenin was an effective augmentation for memantine in the treatment of AD and did not cause more drug-related side-effects. This novel method is worthy of further investigation.

Topics: Activities of Daily Living; Aged; Allylbenzene Derivatives; Alzheimer Disease; Anisoles; Cognition; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Humans; Male; Memantine; Nootropic Agents; Treatment Outcome

This study was aimed to investigate the protective effect and mechanism of β-asarone on the animal model of Alzheimer's disease(AD) which was induced by intracerebroventricular injection of Aβ₁₋₄₂ combined cerebral ischemia. One hundred and five rats were randomly divided into seven groups including sham-operated group, AD model group, β-asarone 10 mg•kg⁻¹ group, β-asarone 20 mg•kg⁻¹ group, β-asarone 30 mg•kg⁻¹ group, donepezil group(0.75 mg•kg⁻¹) and Ginkgo biloba extract group(24 mg•kg⁻¹). Rats' learning and memory abilities, cerebric regional blood flow, pathological changes in hippocampal CA1 region, the expression level of HIF-1α and serum CAT, SOD and MDA level were detected 4 weeks later. The results showed that the application of intracerebroventricular injection of Aβ₁₋₄₂ joint 2-VO could lead to rats' dysfunction of learning and memory, decrease in regional cerebral blood flow. Neurons in CA1 region were arranged in disorder, and amyloid deposition was increased. The number of cerebral cortical cells expressing HIF-1α was increased as well. The level of serum CAT and SOD decreased, while level of serum MDA increased. However these symptoms were improved by 20 mg•kg⁻¹ and 30 mg•kg⁻¹ β-asarone. The results indicated that β-asarone could effectively relieve the symptoms of the AD model induced by intracerebroventricular injection of Aβ₁₋₄₂ combined cerebral ischemia, and the potential mechanism might be that it could attenuate damage of MDA to the body by improving the level of CAT and SOD, meanwhile the level of HIF-1α decreased as the decline of hyperoxide which might attenuate its damage to neuron, so it finally achieved alleviating Alzheimer's disease.

Topics: Allylbenzene Derivatives; Alzheimer Disease; Amyloid beta-Peptides; Animals; Anisoles; Catalase; Disease Models, Animal; Malondialdehyde; Oxidative Stress; Peptide Fragments; Rats; Superoxide Dismutase

Elevated β-amyloid (Aβ) is a hallmark of Alzheimer's disease (AD). Recent evidence has suggested that the receptor of advanced glycation end products (RAGE) is a key target for Aβ-induced perturbation in AD, and blockade of RAGE significantly alleviates synaptic injury. Our previous study has suggested that β-asarone could reduce neuronal apoptosis and improve memory deficits in β-amyloid precursor protein and presenilin-1 (APP/PS1) double transgenic AD-model mice. In the present study, we evaluated the effects of β-asarone on amyloidosis in APP/PS1 mice. We found that the survival of neurons of APP/PS1 mice was improved by β-asarone, meanwhile, β-asarone decreased Aβ deposition and down-regulated Aβ1-42 levels in cortex and hippocampus of APP/PS1 mice brain. Interestingly, the level of RAGE was also significantly down-regulated by β-asarone. Our findings suggest that β-asarone might be effective for the treatment of AD, and the decreasing effects of β-asarone on Aβ might associate with its down-regulation of RAGE.

Topics: Allylbenzene Derivatives; Alzheimer Disease; Amyloid beta-Peptides; Amyloidosis; Animals; Anisoles; Cell Survival; Cerebral Cortex; Disease Models, Animal; Down-Regulation; Hippocampus; Mice, Transgenic; Neurons; Plaque, Amyloid; Presenilin-1; Receptor for Advanced Glycation End Products

β-asarone, an active component of Acori graminei rhizome, has been reported to have neuroprotective effects in Alzheimer's disease. As the underlying mechanism is not known, we investigated the neuroprotective effects of β-asarone in an APP/PS1 double transgenic mouse model and in NG108 cells.. APPswe/PS1dE9 double transgenic male mice were randomly assigned to a model group, β-asarone treatment groups (21.2, 42.4, or 84.8 mg/kg/d), or donepezil treatment group (2 mg/kg/d). Donepezil treatment was a positive control, and background- and age-matched wild-type B6 mice were an external control group. β-asarone (95.6% purity) was dissolved in 0.8% Tween 80 and administered by gavage once daily for 2.5 months. Control and model animals received an equal volume of vehicle. After 2.5 months of treatment, behavior of all animals was evaluated in a Morris water maze. Expression of synaptophysin (SYP) and glutamatergic receptor 1 (G1uR1) in the hippocampus and cortex of the double transgenic mice was assayed by Western blotting. The antagonistic effects of β-asarone against amyloid-β peptide (Aβ) were investigated in vitro in the NG108-15 cell line. After 24 hours of incubation, cells were treated with 10 μm Aβ with or without β-asarone at different concentrations (6.25, 12.5, or 25 μM) for an additional 36 hours. The cytotoxicity of β-asarone was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay of cell viability, and cell morphology was evaluated by bright-field microscopy after 24 hours of treatment. The expression of SYP and GluR1 in cells was detected by Western blot assay in the hippocampus and brain cortex tissues of mice.. β-asarone at a high dose reduced escape latency and upregulated SYP and GluR1 expression at both medium and high doses. Cell morphology evaluation showed that β-asarone treatment did not result in obvious cell surface spots and cytoplasmic granularity. β-asarone had a dose-dependent effect on cell proliferation.. β-asarone antagonized the Aβ neurotoxicity in vivo, improved the learning and memory ability of APP/PS1 mice, and increased the expression of SYP and GluR1 both in vivo and in vitro. Thus, β-asarone may be a potential drug for the treatment of Alzheimer's disease.

Topics: Allylbenzene Derivatives; Alzheimer Disease; Animals; Anisoles; Cells, Cultured; Dose-Response Relationship, Drug; Male; Maze Learning; Mice; Mice, Transgenic; Molecular Structure; Neuronal Plasticity; Neuroprotective Agents; Receptors, AMPA; Structure-Activity Relationship; Synaptophysin

Aberrant neural progenitor cell (NPC) proliferation and self-renewal have been linked to age-related neurodegeneration and neurodegenerative disorders including Alzheimer's disease (AD). Rhizoma Acori tatarinowii is a traditional Chinese herbal medicine against cognitive decline. In this study, we found that the extract of Rhizoma Acori tatarinowii (AT) and its active constituents, asarones, promote NPC proliferation. Oral administration of AT enhanced NPC proliferation and neurogenesis in the hippocampi of adult and aged mice as well as that of transgenic AD model mice. AT and its fractions also enhanced the proliferation of NPCs cultured in vitro. Further analysis identified α-asarone and β-asarone as the two active constituents of AT in promoting neurogenesis. Our mechanistic study revealed that AT and asarones activated extracellular signal-regulated kinase (ERK) but not Akt, two critical kinase cascades for neurogenesis. Consistently, the inhibition of ERK activities effectively blocked the enhancement of NPC proliferation by AT or asarones. Our findings suggest that AT and asarones, which can be orally administrated, could serve as preventive and regenerative therapeutic agents to promote neurogenesis against age-related neurodegeneration and neurodegenerative disorders.

Topics: Acorus; Age Factors; Allylbenzene Derivatives; Alzheimer Disease; Animals; Anisoles; Cell Proliferation; Cells, Cultured; Disease Models, Animal; Drugs, Chinese Herbal; Extracellular Signal-Regulated MAP Kinases; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neural Stem Cells; Neurogenesis

Recent studies have suggested that β-asarone have neuroprotective and cardiovascular protective effects in animal model. However, the influence of β-asarone on cerebrovascular system has not been explored so far. Therefore, present study was designed to determine whether repeated exposures to β-asarone resulted in positive effects on cerebrovascular function in AD rats.. Alzheimer's disease induced rats was established by injecting both D-galactose (D-gal) and aluminum chloride (AlCl(3)) into abdominal cavity for 42 days. After injection of AlCl(3) and D-gal or saline for 28 days, the rats were treated with volume-matched vehicle or β-asarone (25mg/kg, 50mg/kg or 100mg/kg, i.h.) or Nimodipine (40mg/kg, i.g) once daily for consecutive 14 days, respectively. Behavioral responses of animals were assessed in a Morris water maze. CBF was measured by laser Doppler flowmetry. At the end of this period all rats were sacrificed, lactic acid, pyruvic acid content, Na+K+ATPase activity were determined in brain tissue homogenate to estimate the brain biochemical changes and mRNA expression of ET-1, eNOS and APP was measured with real-time RT-PCR method.. The spatial navigation task latencies, the times through platform zone and the time for the first through platform zone in the target quadrant in probe task, rCBF of right parietal lobe, the contents of lactic acid, pyruvic acid, and the activity of Na-K-ATP of cortex, and ET-1 and eNOS mRNA expression in hippocampus of AG rats were different from those of BG, P<0.05; The level of APP mRNA expression in model control group rats was higher than that in BG, though there was not a statistically significant difference, P>0.05; Compared with AG, HG rats spatial navigation task latencies were shorter, in probe task the times through platform zone in the target quadrant were bigger, rCBF and blood cell concentration of right parietal lobe were higher, the contents of pyruvic acid was lower, the activity of Na-K-ATP was higher, and ET-1 mRNA expression in hippocampus was lower, P<0.05; The level of eNOS and APP mRNA expression in HG rats was lower than that in AG, though there was not a statistically significant difference, P>0.05;. The present results suggested that β-asarone may be useful in memory impairment due to its cerebrovascular protection in AD rats and may develop as a therapeutic drug for treatment of AD patients.

Topics: Allylbenzene Derivatives; Aluminum Chloride; Aluminum Compounds; Alzheimer Disease; Amyloid beta-Protein Precursor; Animals; Anisoles; Behavior, Animal; Cerebrovascular Circulation; Chlorides; Endothelin-1; Female; Galactose; Maze Learning; Memory; Nitric Oxide Synthase Type III; Phytotherapy; Protective Agents; Rats; Rats, Wistar; RNA, Messenger

Neurodegenerative disorders, such as Alzheimer's disease (AD), is associated with the loss of neuronal cells, and it has been suggested that apoptosis is a crucial pathway in neuronal loss in AD patients. Recent evidence suggests that amyloid beta peptide (Abeta) induces neuronal apoptosis in the brain and in primary neuronal cultures. In this study, we investigated the impact of beta-asarone against the apoptosis induced by Abeta in rat hippocampus. The results showed that intrahippocampal injections of Abeta (1-42) caused apoptosis in rat hippocampus. Oral administration of beta-asarone (12.5, 25, or 50 mg/kg) for 28 d reverse the increase in the number of terminal deoxynucleotidyl transferase dUTP nick-end labeling positive cells in the hippocampus tissue. Mitochondrial dysfunction is a hallmark of beta-amyloid (Abeta)-induced neuronal toxicity in AD. Therefore, we investigated nuclear translocation of apoptosis induction factors. Our results showed that beta-asarone afforded a beneficial inhibition on both mRNA and protein expression of Bad, Bax, and cleavage of caspases 9 in rat hippocampus following intrahippocampal injections of Abeta (1-42). Our further investigation revealed that ASK1, p-MKK7, and p-c-Jun were significantly decreased after beta-asarone treatment, implicating that the modulation of ASK1/c-JNK-mediated intracellular signaling cascades might be involved in therapeutic effect of beta-asarone against Abeta toxicity. Taken together, these results suggest that beta-asarone may be a potential candidate for development as a therapeutic agent for AD.

Topics: Administration, Oral; Allylbenzene Derivatives; Alzheimer Disease; Amyloid beta-Peptides; Animals; Anisoles; Apoptosis; bcl-2-Associated X Protein; bcl-Associated Death Protein; Caspase 9; DNA Nucleotidylexotransferase; Drug Design; Hippocampus; JNK Mitogen-Activated Protein Kinases; Male; MAP Kinase Kinase Kinase 5; Neurons; Peptide Fragments; Rats; Rats, Sprague-Dawley; Signal Transduction