NMR-Driven Identification of Cinnamon Bud and Bark Components With Anti-Aβ Activity (original) (raw)
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PLoS ONE, 2011
An increasing body of evidence indicates that accumulation of soluble oligomeric assemblies of b-amyloid polypeptide (Ab) 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 Ab plaque formation by compounds from natural sources. Yet, evidence for the ability of common edible elements to modulate Ab oligomerization remains an unmet challenge. Here we identify a natural substance, based on cinnamon extract (CEppt), which markedly inhibits the formation of toxic Ab oligomers and prevents the toxicity of Ab 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 Ab in their brain. Furthermore, oral administration of CEppt to an aggressive AD transgenic mice model led to marked decrease in 56 kDa Ab oligomers, reduction of plaques and improvement in cognitive behavior. Our results present a novel prophylactic approach for inhibition of toxic oligomeric Ab species formation in AD through the utilization of a compound that is currently in use in human diet.
Cinnamon extract inhibits tau aggregation associated with Alzheimer's disease in vitro
Journal of Alzheimer's disease : JAD, 2009
An aqueous extract of Ceylon cinnamon (C. zeylanicum) is found to inhibit tau aggregation and filament formation, hallmarks of Alzheimer's disease (AD). The extract can also promote complete disassembly of recombinant tau filaments and cause substantial alteration of the morphology of paired-helical filaments isolated from AD brain. Cinnamon extract (CE) was not deleterious to the normal cellular function of tau, namely the assembly of free tubulin into microtubules. An A-linked proanthocyanidin trimer molecule was purified from the extract and shown to contain a significant proportion of the inhibitory activity. Treatment with polyvinylpyrolidone effectively depleted all proanthocyanidins from the extract solution and removed the majority, but not all, of the inhibitory activity. The remainder inhibitory activity could be attributed to cinnamaldehyde. This work shows that compounds endogenous to cinnamon may be beneficial to AD themselves or may guide the discovery of other pot...
NMR-driven identification of anti-amyloidogenic compounds in green and roasted coffee extracts
Food chemistry, 2018
To identify food and beverages that provide the regular intake of natural compounds capable of interfering with toxic amyloidogenic aggregates, we developed an experimental protocol that combines NMR spectroscopy and atomic force microscopy, in vitro biochemical and cell assays to detect anti-Aβ molecules in natural edible matrices. We applied this approach to investigate the potential anti-amyloidogenic properties of coffee and its molecular constituents. Our data showed that green and roasted coffee extracts and their main components, 5-O-caffeoylquinic acid and melanoidins, can hinder Aβ on-pathway aggregation and toxicity in a human neuroblastoma SH-SY5Y cell line. Coffee extracts and melanoidins also counteract hydrogen peroxide- and rotenone-induced cytotoxicity and modulate some autophagic pathways in the same cell line.
Metabolites
Various species of cinnamon (Cinnamomum sp.) are consumed as traditional medicine and popular spice worldwide. The current research aimed to provide the first comparative metabolomics study in nine cinnamon drugs and their different commercial preparations based on three analytical platforms, i.e., solid-phase microextraction coupled to gas chromatography–mass spectrometry method (SPME/GC–MS), nuclear magnetic resonance (NMR), and ultraviolet-visible spectrophotometry (UV/Vis) targeting its metabolome. SPME/GC–MS of cinnamon aroma compounds showed a total of 126 peaks, where (E)-cinnamaldehyde was the major volatile detected at 4.2–60.9% and 6.3–64.5% in authenticated and commercial preparations, respectively. Asides, modeling of the GC/MS dataset could relate the commercial products CP-1 and CP-3 to C. cassia attributed to their higher coumarin and low (E)-cinnamaldehyde content. In contrast, NMR fingerprinting identified (E)-methoxy cinnamaldehyde and coumarin as alternative marke...
Prediction of Anti-Alzheimer's Activity of Flavonoids Targeting Acetylcholinesterase in silico
Phytochemical Analysis, 2017
Prediction of anti-Alzheimer's activity of flavonoids targeting acetylcholinesterase in silico http://researchonline.ljmu.ac.uk/id/eprint/5218/ Article LJMU has developed LJMU Research Online for users to access the research output of the University more effectively. and Talukdar, AD (2017) Prediction of anti-Alzheimer's activity of flavonoids targeting acetylcholinesterase in silico. Phytochemical Analysis, 28 (4). pp. 324-331.
bioNMR-based identification of natural anti-Aβ compounds in Peucedanum ostruthium
Bioorganic Chemistry, 2019
The growing interest in medicinal plants for the identification of new bioactive compounds and the formulation of new nutraceuticals and drugs prompted us to develop a powerful experimental approach allowing the detailed metabolic profiling of complex plant extracts, the identification of ligands of macromolecular targets of biomedical relevance and a preliminary characterization of their biological activity. To this end, we selected Peucedanum ostruthium, a plant traditionally employed in Austria and Italy for its several potential therapeutic applications, as case study. We combined the use of NMR and UPLC-HR-MS for the identification of the metabolites present in its leaves and rhizome extracts. Due to the significant content of polyphenols, particularly chlorogenic acids, recently identified as anti-amyloidogenic compounds, polyphenols-enriched fractions were prepared and tested for their ability to prevent Aβ1-42 peptide aggregation and neurotoxicity in a neuronal human cell line. STD-NMR experiments allowed the detailed identification of Aβ oligomers' ligands responsible for the anti-amyloidogenic activity. These data provide experimental protocols and structural information suitable for the development of innovative molecular tools for prevention, therapy and diagnosis of Alzheimer's disease.
Jurnal Kimia Sains dan Aplikasi
Alzheimer’s is a progressive and neurodegenerative disease that mainly affects people aged 65 years and older. The pathophysiology of Alzheimer’s is possibly related to the depletion of the neurotransmitter acetylcholine (ACh) due to beta-amyloid plaques and neurofibrillary tangles. Secondary metabolites found in cinnamon bark (Cinnamomum burmannii) have the potential as anticholinesterases to treat Alzheimer’s symptoms. This study aimed to identify the potency of bioactive compounds from cinnamon bark as AChE inhibitors in silico through analysis of binding energy, inhibition constants, and types of interactions. The research was conducted by screening virtually 60 test ligands using the PyRx program and molecular docking using the Autodock Tools program. The results of the ligand-receptor interaction analysis showed that 12 of the 15 tested ligands had potential as AChE inhibitors. Epicatechin and medioresinol are the ligands with the best potential for AChE inhibition with affini...
Cinnamon (Cinnamomum spp.) is a time-honored species that has been used as a medicine, spice, and flavoring agent for millennia. Some forms of cinnamon are useful in treating neurological disorders including Alzheimer's disease (AD). However, the mechanisms of action are unclear. To elucidate the potential therapeutic value of mechanism, cinnamon ingredients and targets were determined by searching diverse herb databases. AD targets were searched on GeneCards and filtered by reprocessing scRNA-Seq data, which were filtered by STRING to construct the Herb-Ingredient-Target-Disease network. The intersection with AD targets (3445) gave a cinnamon-AD common target set (321). Metascape analysis revealed an enriched pathway/GO process and 123 genes enriched in the Alzheimer's disease pathway were targeted for 78 cinnamon phytochemical components. Effective compounds including eugenol, cinnamaldehyde and coumarin, mainly function against hub targets, for which the binding was validated through molecular docking and dynamics simulation, e.g., cinnamaldehyde against ACHE, PTGS2. Data gathered here suggests that cinnamon may promote anti-Aß aggregation and clearance and modulate the calcium signaling pathway. It provides a therapeutic basis for (hybrid) drug development of cinnamon extracts. Ultimately this study contributes to understanding the mechanism of action of cinnamon constituent metabolites in the treatment of AD.
Evaluation of Plant Phenolic Metabolites as a Source of Alzheimer's Drug Leads
BioMed Research International, 2014
Epidemiological studies have proven an association between consumption of polyphenols and prevention of Alzheimer’s disease, the most common form of dementia characterized by extracellular deposition of amyloid beta plaques. The aim of this study is pharmacological screening of the aqueous alcohol extract ofMarkhamia platycalyxleaves,Schotia brachypetalaleaves and stalks, and piceatannol compared to aqueous alcohol extract ofCamellia sinensisleaves as potential Alzheimer’s disease drugs. LC-HRESI(-ve)-MSnwas performed to identify phenolics’ profile ofSchotia brachypetalastalks aqueous alcohol extract and revealed ten phenolic compounds as first report: daidzein, naringin, procyanidin isomers, procyanidin dimer gallate, quercetin 3-O-rhamnoside, quercetin 3-O-glucuronide, quercetin hexose gallic acid, quercetin hexose protocatechuic acid, and ellagic acid. Alzheimer’s disease was induced by a single intraperitoneal injection of LPS. Adult male Swiss albino mice were divided into grou...
Alzheimer's disease (AD) is the main cause of dementia in people over 65 years. One of the major culprits in AD is the self-aggregation of amyloid-β peptide (Aβ), which has stimulated the search for small molecules able to inhibit Aβ aggregation. In this context, we recently reported a simple, but effective in vitro cell-based assay to evaluate the potential antiaggregation activity of putative Aβ aggregation inhibitors. In this work this assay was used together with docking and molecular dynamics simulations to analyze the anti-Aβ aggregation activity of several naturally occurring flavonoids and phenolic compounds. The results showed that rosmarinic acid, melatonin, and o-vanillin displayed zero or low inhibitory capacity, curcumin was found to have an intermediate inhibitory potency, and apigenin and quercetin showed potent antiaggregation activity. Finally, the suitability of the combined in vitro cell-based/in silico approach to distinguish between active and inactive compounds was further assessed for an additional set of flavonols and dihydroflavonols. A lzheimer's disease (AD) is the leading cause of dementia in people over 65. In 2010 there were 36 million people affected worldwide, and the number is expected to triple in 2050. 1,2 AD is a chronic, progressive, and currently incurable illness characterized by the progressive loss of the capacity to create new memories as well as confusion, language difficulties, personality changes, and depression, among others. Two distinctive hallmarks characterize the brain physiopathology of AD patients: (1) the formation of extracellular amyloid plaques originating from the aggregation of amyloid-β peptide (Aβ) and (2) neurofibrillary tangles, which are primarily formed by hyperphosphorylated forms of neuronal tau protein associated in microtubules. 3,4 Extracellular amyloid plaques and neuro-fibrillary tangles lead to nerve cell death and tissue loss throughout the brain. In the brain the cortex shrivels up, initially damaging areas involved in cognition (primarily in the formation of new memories) and language, mainly affecting the Broca's and Wernicke's areas in the hippocampus. Even though the precise etiology of AD still remains to be completely understood, age is the major risk factor, often regulated by environmental factors and genetic mutations. 5