Orally Administrated Cinnamon Extract Reduces β-Amyloid Oligomerization and Corrects Cognitive Impairment in Alzheimer's Disease Animal Models
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{"title"=>"Orally administrated cinnamon extract reduces β-amyloid oligomerization and corrects cognitive impairment in Alzheimer's disease animal models", "type"=>"journal", "authors"=>[{"first_name"=>"Anat", "last_name"=>"Frydman-Marom", "scopus_author_id"=>"13003555100"}, {"first_name"=>"Aviad", "last_name"=>"Levin", "scopus_author_id"=>"57197036911"}, {"first_name"=>"Dorit", "last_name"=>"Farfara", "scopus_author_id"=>"24328648400"}, {"first_name"=>"Tali", "last_name"=>"Benromano", "scopus_author_id"=>"36917893300"}, {"first_name"=>"Roni", "last_name"=>"Scherzer-Attali", "scopus_author_id"=>"36237671300"}, {"first_name"=>"Sivan", "last_name"=>"Peled", "scopus_author_id"=>"23103843200"}, {"first_name"=>"Robert", "last_name"=>"Vassar", "scopus_author_id"=>"35570436300"}, {"first_name"=>"Daniel", "last_name"=>"Segal", "scopus_author_id"=>"7202933261"}, {"first_name"=>"Ehud", "last_name"=>"Gazit", "scopus_author_id"=>"7101668029"}, {"first_name"=>"Dan", "last_name"=>"Frenkel", "scopus_author_id"=>"7005702282"}, {"first_name"=>"Michael", "last_name"=>"Ovadia", "scopus_author_id"=>"7004749535"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-79551537131", "sgr"=>"79551537131", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0016564", "pmid"=>"21305046", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pui"=>"361204431"}, "id"=>"b29ffffb-6856-3b25-b286-23f359e9b467", "abstract"=>"An increasing body of evidence indicates that accumulation of soluble oligomeric assemblies of β-amyloid polypeptide {(Aβ)} play a key role in Alzheimer's disease {(AD)} pathology. Specifically, 56 {kDa} oligomeric species were shown to be correlated with impaired cognitive function in {AD} model mice. Several reports have documented the inhibition of Aβ plaque formation by compounds from natural sources. Yet, evidence for the ability of common edible elements to modulate Aβ oligomerization remains an unmet challenge. Here we identify a natural substance, based on cinnamon extract {(CEppt),} which markedly inhibits the formation of toxic Aβ oligomers and prevents the toxicity of Aβ on neuronal {PC12} cells. When administered to an {AD} fly model, {CEppt} rectified their reduced longevity, fully recovered their locomotion defects and totally abolished tetrameric species of Aβ in their brain. Furthermore, oral administration of {CEppt} to an aggressive {AD} transgenic mice model led to marked decrease in 56 {kDa} Aβ oligomers, reduction of plaques and improvement in cognitive behavior. Our results present a novel prophylactic approach for inhibition of toxic oligomeric Aβ species formation in {AD} through the utilization of a compound that is currently in use in human diet.", "link"=>"http://www.mendeley.com/research/orally-administrated-cinnamon-extract-reduces-%CE%B2amyloid-oligomerization-corrects-cognitive-impairment", "reader_count"=>100, "reader_count_by_academic_status"=>{"Unspecified"=>4, "Professor > Associate Professor"=>3, "Librarian"=>1, "Researcher"=>17, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>31, "Student > Postgraduate"=>4, "Other"=>6, "Student > Master"=>17, "Student > Bachelor"=>10, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>4, "Professor > Associate Professor"=>3, "Librarian"=>1, "Researcher"=>17, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>31, "Student > Postgraduate"=>4, "Other"=>6, "Student > Master"=>17, "Student > Bachelor"=>10, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>7, "Agricultural and Biological Sciences"=>45, "Arts and Humanities"=>1, "Business, Management and Accounting"=>1, "Chemistry"=>9, "Earth and Planetary Sciences"=>1, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>2, "Medicine and Dentistry"=>19, "Neuroscience"=>5, "Physics and Astronomy"=>3, "Psychology"=>3, "Social Sciences"=>2, "Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>19}, "Social Sciences"=>{"Social Sciences"=>2}, "Physics and Astronomy"=>{"Physics and Astronomy"=>3}, "Psychology"=>{"Psychology"=>3}, "Unspecified"=>{"Unspecified"=>7}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "Arts and Humanities"=>{"Arts and Humanities"=>1}, "Engineering"=>{"Engineering"=>1}, "Chemistry"=>{"Chemistry"=>9}, "Neuroscience"=>{"Neuroscience"=>5}, "Earth and Planetary Sciences"=>{"Earth and Planetary Sciences"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>45}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}}, "reader_count_by_country"=>{"Austria"=>1, "South Korea"=>1, "Belgium"=>1, "United States"=>2, "United Kingdom"=>1, "France"=>2, "Germany"=>1}, "group_count"=>2}

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  • {"files"=>["https://ndownloader.figshare.com/files/803388"], "description"=>"<p>(A) Samples of Aβ<sub>42</sub> (20 µg/ml) with or without various concentrations of CEppt were incubated for 24 hours with PC12 cells culture. To exclude any toxic effect of CEppt, CEppt alone (9 µg/ml) was pre-incubated for 24 hours with PC12 cells (ref CEppt). Cells viability was determined using MTT viability assay. ** Pv<0.005. (B) The effect of CEppt on longevity of Aβ<sub>42</sub>-expressing flies. The life span of four classes of flies was evaluated. AD flies grown on regular medium (black line), AD flies grown on medium containing CEppt (black dashed line), Control Flies (carrying the Aβ<sub>42</sub> transgene but not expressing it) grown on regular medium (grey line), Control Flies (carrying the Aβ<sub>42</sub> transgene but not expressing it) grown on medium containing CEppt (grey dashed line). (C) The effect of CEppt on the climbing behavior of Aβ<sub>42</sub>-expressing flies. Four classes, each containing six-nine vials with 10 flies in each: AD flies grown on regular medium (black),AD flies grown on medium containing CEppt (grey), Control flies (carrying the Aβ<sub>42</sub> transgene but not expressing it) grown on either regular medium (striped) or on medium containing CEppt (white), were analyzed using the climbing assay. Results show the percent of flies climbing to the top of the vial after 18 seconds, during the course of 10 days. Pv<0.0001. (D) Head extract from 4 days old flies. OR-control flies (left), AβArc<sub>42</sub>-expressing flies unfed (middle) fed with 0.75 mg/mL CEppt (right) (n = 40 in each group). Accumulation of Aβ tetramers is evident only in AβArc<sub>42</sub> flies which were not fed with CEppt.</p>", "links"=>[], "tags"=>["alleviates"], "article_id"=>473745, "categories"=>["Biochemistry", "Neuroscience", "Biophysics"], "users"=>["Anat Frydman-Marom", "Aviad Levin", "Dorit Farfara", "Tali Benromano", "Roni Scherzer-Attali", "Sivan Peled", "Robert Vassar", "Daniel Segal", "Ehud Gazit", "Dan Frenkel", "Michael Ovadia"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0016564.g002", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CEppt_alleviates_toxic_effects_of_A_946_8211_cell_and_fly_assays_/473745", "title"=>"CEppt alleviates toxic effects of Aβ – cell and fly assays.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-01-28 01:02:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/803255"], "description"=>"<p>(A) Determination of a dose-dependent effect of CEppt on soluble off-pathway oligomer formation. Soluble oligomers were prepared <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0016564#pone.0016564-Barghorn1\" target=\"_blank\">[10]</a> with and without increasing concentration of CEppt. Concentration ratios (w/w) of CEppt: Aβ<sub>42</sub> are indicated. The control is Aβ<sub>42</sub> (0.6 mg/ml) alone. (B) The kinetics of Aβ<sub>40</sub> (20 µg/ml) fibril formation with and without the inhibitor as assessed by the Thioflavin-T biding assay over the course of 264 hours. Concentrations are expressed as CEppt: Aβ<sub>40</sub> concentration ratio (w/w). Control - Aβ<sub>40</sub> only (▪); 5∶1 (*); 1∶2 (o); 1∶20 (▾); 1∶200 (•); 1∶2000 (▸). (C) Endpoint of ThT analysis measurement T = 264 hours. Concentrations are expressed as CEppt: Aβ<sub>40</sub> concentration ratio (w/w), control is Aβ<sub>40</sub> (20 µg/ml). (D–G) Transmission electron microscope images taken from ThT analysis after 264 hours. (D)Aβ<sub>40</sub> alone, (E) CEppt:Aβ<sub>40</sub> (1∶20), (F) CEppt:Aβ<sub>40</sub> (1∶2), (G) CEppt:Aβ<sub>40</sub> (5∶1), (H) Samples of Aβ<sub>40</sub> (20 µg/ml) was incubated alone (▪) or with the addition of CEppt (100 µg/ml) at various time points of Aβ aggregation,Aβ aggregation was monitored by ThT assay. CEppt was added at 0 hour (◂); 24 hours (•) and 72 hours (▾). (I–L) Transmission electron microscope of samples taken from the disaggregation assay after 200 hr. (I) Aβ<sub>40</sub> alone, (J) T = 0 hour, (K) T = 24 hours, (L) T = 72 hours.</p>", "links"=>[], "tags"=>["disaggregation", "assemblies"], "article_id"=>473610, "categories"=>["Biochemistry", "Neuroscience", "Biophysics"], "users"=>["Anat Frydman-Marom", "Aviad Levin", "Dorit Farfara", "Tali Benromano", "Roni Scherzer-Attali", "Sivan Peled", "Robert Vassar", "Daniel Segal", "Ehud Gazit", "Dan Frenkel", "Michael Ovadia"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0016564.g001", "stats"=>{"downloads"=>2, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Inhibition_and_disaggregation_of_A_assemblies_in_vitro_/473610", "title"=>"Inhibition and disaggregation of Aβ assemblies <i>in vitro.</i>", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-01-28 01:00:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/803683"], "description"=>"<p>(A) Histological images of frontal cortex sections stained with Aβ antibody 6E10 from vehicle-treated 5XFAD mice, and (B) CEppt-treated 5XFAD mice. (C) Histological images of frontal cortex sections stained with Congo red from vehicle-treated 5XFAD mice, and (D) CEppt-treated 5XFAD mice. Scale bar = 100 µm. (E) Quantification of the % plaque load area of hippocampal sections from 5XFAD mice with or without CEppt treatment determined by 6E10 staining. (F) Quantification of the % plaque load area of hippocampal sections from 5XFAD mice with or without CEppt treatment determined by Congo red staining.</p>", "links"=>[], "tags"=>["ceppt", "plaques", "5xfad"], "article_id"=>474041, "categories"=>["Biochemistry", "Neuroscience", "Biophysics"], "users"=>["Anat Frydman-Marom", "Aviad Levin", "Dorit Farfara", "Tali Benromano", "Roni Scherzer-Attali", "Sivan Peled", "Robert Vassar", "Daniel Segal", "Ehud Gazit", "Dan Frenkel", "Michael Ovadia"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0016564.g004", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_effect_of_CEppt_on_A_946_plaques_formation_in_5XFAD_Alzheimer_s_disease_model_mice_/474041", "title"=>"The effect of CEppt on Aβ plaques formation in 5XFAD Alzheimer's disease model mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-01-28 01:07:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/803513"], "description"=>"<p>(A) Object recognition test of transgenic AD model mice (5XFAD), non-transgenic littermate (W.T.), and 5XFAD treated mice. Placebo 5XFAD mice were given drinking water (n = 8); W.T mice were given drinking water (n = 8); treated 5XFAD mice were given water with CEppt (100 µg/ml) (n = 7). One-way ANOVA tests show Pv = 0.0413. (B) Soluble fraction of mouse brain homogenates were analyzed by western blot probed with Aβ antibody 6E10. (C) Western blot band signals for 56 kDa in (B) were quantified using densitometry and displayed as Percent of 56 kDa toxic oligomer band intensity. (D) Insoluble fraction of mouse brain homogenates were analyzed by western blot probed with Aβ antibody 6E10, quantified using densitometry, and displayed as relative intensities of total Aβ signals.</p>", "links"=>[], "tags"=>["ceppt", "performances", "oligomer", "5xfad"], "article_id"=>473866, "categories"=>["Biochemistry", "Neuroscience", "Biophysics"], "users"=>["Anat Frydman-Marom", "Aviad Levin", "Dorit Farfara", "Tali Benromano", "Roni Scherzer-Attali", "Sivan Peled", "Robert Vassar", "Daniel Segal", "Ehud Gazit", "Dan Frenkel", "Michael Ovadia"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0016564.g003", "stats"=>{"downloads"=>3, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_effect_of_CEppt_on_cognitive_performances_and_A_946_oligomer_formation_in_5XFAD_Alzheimer_s_disease_model_mice_/473866", "title"=>"The effect of CEppt on cognitive performances and Aβ oligomer formation in 5XFAD Alzheimer's disease model mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-01-28 01:04:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/400875", "https://ndownloader.figshare.com/files/400926", "https://ndownloader.figshare.com/files/400962", "https://ndownloader.figshare.com/files/400992"], "description"=>"<div><p>An increasing body of evidence indicates that accumulation of soluble oligomeric assemblies of β-amyloid polypeptide (Aβ) play a key role in Alzheimer's disease (AD) pathology. Specifically, 56 kDa oligomeric species were shown to be correlated with impaired cognitive function in AD model mice. Several reports have documented the inhibition of Aβ plaque formation by compounds from natural sources. Yet, evidence for the ability of common edible elements to modulate Aβ oligomerization remains an unmet challenge. Here we identify a natural substance, based on cinnamon extract (CEppt), which markedly inhibits the formation of toxic Aβ oligomers and prevents the toxicity of Aβ on neuronal PC12 cells. When administered to an AD fly model, CEppt rectified their reduced longevity, fully recovered their locomotion defects and totally abolished tetrameric species of Aβ in their brain. Furthermore, oral administration of CEppt to an aggressive AD transgenic mice model led to marked decrease in 56 kDa Aβ oligomers, reduction of plaques and improvement in cognitive behavior. Our results present a novel prophylactic approach for inhibition of toxic oligomeric Aβ species formation in AD through the utilization of a compound that is currently in use in human diet.</p> </div>", "links"=>[], "tags"=>["orally", "administrated", "cinnamon", "extract", "reduces", "oligomerization", "corrects", "impairment", "models"], "article_id"=>139201, "categories"=>["Biochemistry", "Neuroscience", "Biophysics"], "users"=>["Anat Frydman-Marom", "Aviad Levin", "Dorit Farfara", "Tali Benromano", "Roni Scherzer-Attali", "Sivan Peled", "Robert Vassar", "Daniel Segal", "Ehud Gazit", "Dan Frenkel", "Michael Ovadia"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0016564.s001", "https://dx.doi.org/10.1371/journal.pone.0016564.s002", "https://dx.doi.org/10.1371/journal.pone.0016564.s003", "https://dx.doi.org/10.1371/journal.pone.0016564.s004"], "stats"=>{"downloads"=>22, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Orally_Administrated_Cinnamon_Extract_Reduces_Amyloid_Oligomerization_and_Corrects_Cognitive_Impairment_in_Alzheimer_s_Disease_Animal_Models/139201", "title"=>"Orally Administrated Cinnamon Extract Reduces β-Amyloid Oligomerization and Corrects Cognitive Impairment in Alzheimer's Disease Animal Models", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2011-01-28 02:33:21"}

PMC Usage Stats | Further Information

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