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BioMed Research International 2020Neurodegenerative diseases are devastating and incurable disorders characterized by neuronal dysfunction. The major focus of experimental and clinical studies are... (Review)
Review
Neurodegenerative diseases are devastating and incurable disorders characterized by neuronal dysfunction. The major focus of experimental and clinical studies are conducted on the effects of natural products and their active components on neurodegenerative diseases. This review will discuss an herbal constituent known as cinnamaldehyde (CA) with the neuroprotective potential to treat neurodegenerative disorders, such as Alzheimer's disease (AD) and Parkinson's disease (PD). Accumulating evidence supports the notion that CA displays neuroprotective effects in AD and PD animal models by modulating neuroinflammation, suppressing oxidative stress, and improving the synaptic connection. CA exerts these effects through its action on multiple signaling pathways, including TLR4/NF-B, NLRP3, ERK1/2-MEK, NO, and Nrf2 pathways. To summarize, CA and its derivatives have been shown to improve pathological changes in AD and PD animal models, which may provide a new therapeutic option for neurodegenerative interventions. To this end, further experimental and clinical studies are required to prove the neuroprotective effects of CA and its derivatives.
Topics: Acrolein; Animals; Disease Models, Animal; Disease Progression; Humans; Inflammation; Neurodegenerative Diseases; Neuroprotective Agents
PubMed: 33274192
DOI: 10.1155/2020/1034325 -
Environment International Sep 2022Acrolein is a significant high priority hazardous air pollutant with pulmonary toxicity and the leading cause of most noncancer adverse respiratory effects among air...
Cross-sectional and longitudinal associations of acrolein exposure with pulmonary function alteration: Assessing the potential roles of oxidative DNA damage, inflammation, and pulmonary epithelium injury in a general adult population.
BACKGROUND
Acrolein is a significant high priority hazardous air pollutant with pulmonary toxicity and the leading cause of most noncancer adverse respiratory effects among air toxics that draws great attention. Whether and how acrolein exposure impacts pulmonary function remain inconclusive.
OBJECTIVES
To assess the association of acrolein exposure with pulmonary function and the underlying roles of oxidative DNA damage, inflammation, and pulmonary epithelium integrity.
METHODS
Among 3,279 Chinese adults from the Wuhan-Zhuhai cohort, associations of urinary acrolein metabolites (N-Acetyl-S-(2-carboxyethyl)-L-cysteine, CEMA; N-Acetyl-S-(3-hydroxypropyl)-L-cysteine, 3HPMA) as credible biomarkers of acrolein exposure with pulmonary function were analyzed by linear mixed models. Joint effects of biomarkers of oxidative DNA damage (8-hydroxy-deoxyguanosine), inflammation (C-reactive protein, CRP), and pulmonary epithelium integrity (Club cell secretory protein, CC16) with acrolein metabolites on pulmonary function and the mediating roles of these biomarkers were assessed. Besides, a subgroup (N = 138) was randomly recruited from the cohort to assess the stabilities of acrolein metabolites and their longitudinal associations with pulmonary function change in three years.
RESULTS
Significant inverse dose-response relationships between acrolein metabolites and pulmonary function were found. Each 10-fold increment in CEMA, 3HPMA, or ΣUACLM (CEMA + 3HPMA) was cross-sectionally related to a 68.56-, 40.98-, or 46.02-ml reduction in FVC and a 61.54-, 43.10-, or 50.14-ml reduction in FEV, respectively (P < 0.05). Furthermore, acrolein metabolites with fair to excellent stabilities were found to be longitudinally associated with pulmonary function decline in three years. Joint effects of acrolein metabolites with 8-hydroxy-deoxyguanosine, CRP, and CC16 on pulmonary function were identified. CRP significantly mediated 5.97% and 5.51% of CEMA-associated FVC and FEV reductions, respectively. 8-hydroxy-deoxyguanosine significantly mediated 6.78%, 6.88%, and 7.61% of CEMA-, 3HPMA-, and ΣUACLM-associated FVC reductions, respectively.
CONCLUSIONS
Acrolein exposure of general adults was cross-sectionally and longitudinally related to pulmonary function decline, which was aggravated and/or partly mediated by oxidative DNA damage, inflammation, and pulmonary epithelium injury.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Acrolein; Adult; Biomarkers; C-Reactive Protein; Cross-Sectional Studies; Cysteine; Epithelium; Humans; Inflammation; Oxidative Stress
PubMed: 35850081
DOI: 10.1016/j.envint.2022.107401 -
Cytoskeleton (Hoboken, N.J.) Oct 2020We have found recently that dendritic spine extension is inhibited through acrolein conjugation with α- and β-tubulin proteins during brain infarction. In this current...
We have found recently that dendritic spine extension is inhibited through acrolein conjugation with α- and β-tubulin proteins during brain infarction. In this current study, we looked for other acrolein-conjugated proteins in the 100,000g precipitate fraction, to clarify how cytoskeleton structure is modified by acrolein. Acrolein-conjugated proteins were sought from acrolein-treated mouse FM3A and Neuro2a cells and from tissues isolated from mouse brain infarction. It was found that vimentin was conjugated with acrolein, and the conjugated amino acid residue was Cys328, which is the only Cys residue in vimentin. It was also found that Cys207, 257, 285, and Lys118 in actin, another cytoskeleton protein, were conjugated with acrolein. The structure and localization of vimentin and actin filaments were changed greatly in infarct brain in photochemically induced thrombosis model mice and in acrolein-treated Neuro2a cells. In addition, degradation of cytoskeleton proteins was accelerated in the order vimentin > tubulin > actin in mouse brain infarction. These findings indicate that a dysfunction of the cytoskeleton by acrolein is strongly involved in the tissue damage during brain infarction, together with the apoptosis caused by glyceraldehyde-3-phosphate dehydrogenase and protein degradation by matrix metalloproteinase-9.
Topics: Acrolein; Actins; Animals; Brain Infarction; Cytoskeleton; Humans; Male; Mice; Vimentin
PubMed: 33070462
DOI: 10.1002/cm.21638 -
Plant Physiology Feb 2024Lignin is an abundant polymer in plant secondary cell walls. Prototypical lignins derive from the polymerization of monolignols (hydroxycinnamyl alcohols), mainly...
Lignin is an abundant polymer in plant secondary cell walls. Prototypical lignins derive from the polymerization of monolignols (hydroxycinnamyl alcohols), mainly coniferyl and sinapyl alcohol, via combinatorial radical coupling reactions and primarily via the endwise coupling of a monomer with the phenolic end of the growing polymer. Hydroxycinnamaldehyde units have long been recognized as minor components of lignins. In plants deficient in cinnamyl alcohol dehydrogenase, the last enzyme in the monolignol biosynthesis pathway that reduces hydroxycinnamaldehydes to monolignols, chain-incorporated aldehyde unit levels are elevated. The nature and relative levels of aldehyde components in lignins can be determined from their distinct and dispersed correlations in 2D 1H-13C-correlated nuclear magnetic resonance (NMR) spectra. We recently became aware of aldehyde NMR peaks, well resolved from others, that had been overlooked. NMR of isolated low-molecular-weight oligomers from biomimetic radical coupling reactions involving coniferaldehyde revealed that the correlation peaks belonged to hydroxycinnamaldehyde-derived benzofuran moieties. Coniferaldehyde 8-5-coupling initially produces the expected phenylcoumaran structures, but the derived phenolic radicals undergo preferential disproportionation rather than radical coupling to extend the growing polymer. As a result, the hydroxycinnamaldehyde-derived phenylcoumaran units are difficult to detect in lignins, but the benzofurans are now readily observed by their distinct and dispersed correlations in the aldehyde region of NMR spectra from any lignin or monolignol dehydrogenation polymer. Hydroxycinnamaldehydes that are coupled to coniferaldehyde can be distinguished from those coupled with a generic guaiacyl end-unit. These benzofuran peaks may now be annotated and reported and their structural ramifications further studied.
Topics: Lignin; Benzofurans; Aldehydes; Polymers; Acrolein; Cinnamates
PubMed: 37773018
DOI: 10.1093/plphys/kiad514 -
Chemistry (Weinheim An Der Bergstrasse,... Feb 2020Mounting evidence supports the role of amyloidogenesis, oxidative stress, and metal dyshomeostasis in the development of neurodegenerative disorders. Parkinson's Disease...
Mounting evidence supports the role of amyloidogenesis, oxidative stress, and metal dyshomeostasis in the development of neurodegenerative disorders. Parkinson's Disease is characterized by α-synuclein (αSyn) accumulation and aggregation in brain regions, also promoted by Cu . αSyn is modified by reactive carbonyl species, including acrolein (ACR). Notwithstanding these findings, the interplay between ACR, copper, and αSyn has never been investigated. Therefore, we explored more thoroughly the effects of ACR on αSyn using an approach based on LC-MS/MS analysis. We also evaluated the influence of Cu on the protein carbonylation and how the ACR modification impacts the Cu binding and the production of Reactive Oxygen Species (ROS). Finally, we investigated the effects of ACR and Cu ions on the αSyn aggregation by dynamic light scattering and fluorescence assays. Cu regioselectively inhibits the modification of His50 by ACR, the carbonylation lowers the affinity of His50 for Cu and ACR inhibits αSyn aggregation both in the presence and in the absence of Cu .
Topics: Acrolein; Chromatography, High Pressure Liquid; Copper; Dynamic Light Scattering; Humans; Oxidative Stress; Protein Aggregates; Protein Carbonylation; Reactive Oxygen Species; Tandem Mass Spectrometry; alpha-Synuclein
PubMed: 31804737
DOI: 10.1002/chem.201904885 -
Journal of Alzheimer's Disease : JAD 2023Dementia, including Alzheimer's disease (AD), is one of the serious diseases at advanced age, and its early detection is important for maintaining quality of life (QOL).
BACKGROUND
Dementia, including Alzheimer's disease (AD), is one of the serious diseases at advanced age, and its early detection is important for maintaining quality of life (QOL).
OBJECTIVE
In this study, we sought novel biomarkers for dementia in urine.
METHODS
Samples of urine were collected from 57 control subjects without dementia, 62 mild cognitive impairment (MCI) patients, and 42 AD patients. Mini-Mental State Examination (MMSE) was evaluated when subjects were examined by medical doctors. Urinary amino acid (lysine)-conjugated acrolein (AC-Acro) was measured using N ɛ-(3-formyl-3, 4-dehydropiperidine) lysine (FDP-Lys) ELISA kit, and taurine content was measured using a taurine assay kit. Values were normalized by creatinine content which was measured with the colorimetric assay kit.
RESULTS
We found that urinary amino acid (lysine)-conjugated acrolein (AC-Acro) and taurine negatively correlated with MMSE score and are significantly lower in dementia patients compared to the normal subjects. When AC-Acro and taurine were evaluated together with age using an artificial neural network model, median relative risk values for subjects with AD, subjects with mild cognitive impairment, and control subjects were 0.96, 0.53, and 0.06, respectively.
CONCLUSION
Since urine is relatively easy to collect, our findings provide a novel biomarker for dementia without invasiveness.
Topics: Humans; Acrolein; Quality of Life; Lysine; Alzheimer Disease; Cognitive Dysfunction; Biomarkers
PubMed: 36744340
DOI: 10.3233/JAD-220912 -
Toxicology Jan 2022Acrolein is a hazardous air pollutant for humans and is responsible for many pulmonary diseases, but the underlying mechanisms have not been completely elucidated. This...
Acrolein is a hazardous air pollutant for humans and is responsible for many pulmonary diseases, but the underlying mechanisms have not been completely elucidated. This work is focused on the genotoxicity effects of human bronchial epithelial (BEAS-2B) cells induced by acrolein (20, 40, 80 μM). The molecular mechanism was investigated base on DNA damage and mitochondrial apoptosis pathways. The results showed that after exposure to acrolein, the cell viability, glutathione (GSH) of BEAS-2B cells were reduced. Reactive oxygen species (ROS) level significantly increased, accompanied by increased levels of DNA damage-related indicators 8-hydroxy-2 deoxyguanosine (8-OHdG), DNA content of comet tail (Tail DNA%), olive tail moment (OTM), and nucleus morphology. Cell arrested at the G2/M phase. Then, the DNA damage response (DDR) signaling pathway (Ataxia-telangiectasia-mutated (ATM) and Rad-3-related (ATR)/Chk1 and ATM/Chk2) and the consequent cell cycle checkpoints were activated. The expression of γ-H2AX was significantly increased, indicating that acrolein induced DNA double-strand breaks. Molecular docking assay showed that acrolein bound to DNA in a spontaneous process. Moreover, mitochondrial apoptosis pathway involved in apoptosis, mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP) content of BEAS-2B cells were significantly reduced, and the apoptosis rate was significantly increased. The protein expression of Bax/Bcl-2 and Cleaved Caspase-3 were increased, and JNK signaling pathway was activated. All the results indicated that acrolein induced DNA damage, activated DDR and mitochondrial apoptosis pathways, which might be the pivotal factors to mediate cytotoxicity in BEAS-2B cells.
Topics: Acrolein; Apoptosis; Caspase 3; Cell Cycle Checkpoints; Cell Line; Cell Survival; DNA Damage; Epithelial Cells; Glutathione; Histones; Humans; Membrane Potential, Mitochondrial; Mitochondria; Molecular Docking Simulation; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species; Signal Transduction
PubMed: 34958888
DOI: 10.1016/j.tox.2021.153083 -
Critical Reviews in Food Science and... 2023Cinnamaldehyde is an essential oil extracted from the leaves, bark, roots and flowers of cinnamon plants (genus ). Cinnamaldehyde has shown biological functions such as... (Review)
Review
Cinnamaldehyde is an essential oil extracted from the leaves, bark, roots and flowers of cinnamon plants (genus ). Cinnamaldehyde has shown biological functions such as antioxidants, antimicrobials, anti-diabetic, anti-obesity and anti-cancer. However, poor solubility in water as well as molecular sensitivity to oxygen, light, and high temperature limit the direct application of cinnamaldehyde. Researchers are using different encapsulation techniques to maximize the potential biological functions of cinnamaldehyde. Different delivery systems such as liposomes, emulsions, biopolymer nanoparticles, complex coacervation, molecular inclusion, and spray drying have been developed for this purpose. The particle size and morphology, composition and physicochemical properties influence the performance of each delivery system. Consequently, the individual delivery system has its advantages and limitations for specific applications. Given the essential role of cinnamaldehyde in functional food and food preservation, appropriate approaches should be applied in the encapsulation and application of encapsulated cinnamaldehyde. This review systematically analyzes available encapsulation techniques for cinnamaldehyde in terms of their design, properties, advantages and limitations, and food application status. The information provided in this manuscript will assist in the development and widespread use of cinnamaldehyde-loaded particles in the food and beverage industries.
Topics: Anti-Infective Agents; Oils, Volatile; Cinnamomum zeylanicum; Acrolein
PubMed: 34515594
DOI: 10.1080/10408398.2021.1977236 -
Nutrients Aug 2022In this study, the effects of cinnamaldehyde and curcumin on Akt2, a serine/threonine protein kinase central to the insulin signaling pathway, were examined in...
In this study, the effects of cinnamaldehyde and curcumin on Akt2, a serine/threonine protein kinase central to the insulin signaling pathway, were examined in preadipocytes. Cinnamaldehyde or curcumin treatment increased Akt2 phosphorylation at multiple sites including T450 and Y475, but had no effect on Akt2 phosphorylation at S474, which is critical for Akt2 activation. Surprisingly, insulin treatment with cinnamaldehyde or curcumin increased p-Akt2 (S474) by 3.5-fold versus insulin treatment alone. Furthermore, combined cinnamaldehyde, curcumin, and insulin treatment increased p-Akt2 (S474) by 7-fold versus insulin treatment alone. Interestingly, cinnamaldehyde and curcumin inhibited both serine/threonine phosphatase 2A (PP2A) and protein tyrosine phosphatase 1B (PTP1B). Akt2 activation is a multistep process that requires phosphorylation at T450 for proper folding and maturation, and phosphorylation of both Y475 and S474 for stabilization of the catalytic domain. It is plausible that by inhibiting PP2A and PTP1B, cinnamaldehyde and curcumin increase phosphorylation at T450 and Y475, and prime Akt2 for insulin-stimulated phosphorylation at S474. Notably, the combination of a PP2A inhibitor, okadaic acid, and a PTP1B inhibitor increased p-Akt2 (S474), even in the absence of insulin. Future combinations of PP2A and PTP1B inhibitors provide a rational platform to engineer new therapeutics for insulin resistance syndrome.
Topics: Acrolein; Curcumin; Enzyme Inhibitors; Insulin; Phosphorylation; Serine
PubMed: 36014807
DOI: 10.3390/nu14163301 -
Journal of Dermatological Science Dec 2019Ultraviolet (UV) irradiation disrupts skin through several deleterious actions, such as induction of reactive oxygen species (ROS), DNA damage, and collagen degradation....
BACKGROUND
Ultraviolet (UV) irradiation disrupts skin through several deleterious actions, such as induction of reactive oxygen species (ROS), DNA damage, and collagen degradation. Cinnamaldehyde (CIN) is a major constituent of the cinnamon and it possesses potent antioxidative activity; however, it is unclear whether CIN is capable of inhibiting the adverse effects of UVB.
OBJECTIVE
To investigate protective effects of CIN against UVB-induced photodamage.
METHODS
HaCaT keratinocytes were pretreated with CIN, irradiated with UVB, and assessed for the ROS production by flow cytometry and for the DNA damage by ELISA. As in vivo mouse model, Hos:HR-1 hairless mice were treated with ointments containing DMSO or CIN and irradiated multiple times with UVB. After 10 weeks of irradiation, wrinkle formation, epidermal thickness, infiltrating cell number, malondialdehyde amount, collagen amount, MAP kinase signaling, and related gene expressions (Hmox1, Col1a1, Mmp1a, and Mmp13) were analyzed.
RESULTS
CIN significantly reduced the ROS production and accelerated the repair of DNA damage pyrimidine(6-4)pyrimidone photoproducts in UVB-irradiated human keratinocytes in vitro. In the mouse model, topical application of CIN significantly inhibited wrinkle formation, epidermal hyperplasia, and dermal inflammatory cell infiltration. The antioxidative process was significantly promoted in the CIN-applied site, as evidenced by upregulation of the antioxidative enzyme Hmox1 as well as the reduced accumulation of malondialdehyde. In addition, topical application of CIN normalized the UVB-induced collagen/Col1a1 downregulation and the UVB-induced Mmp13 upregulation, implying the prevention of UVB-induced collagen degradation.
CONCLUSIONS
CIN and CIN-containing herbal agents may exert potent protective effects against UVB exposure on skin.
Topics: Acrolein; Animals; Antioxidants; Cell Line; Cinnamomum aromaticum; Collagen Type I; Collagen Type I, alpha 1 Chain; DNA Damage; Female; Heme Oxygenase-1; Humans; Keratinocytes; MAP Kinase Signaling System; Malondialdehyde; Matrix Metalloproteinase 13; Membrane Proteins; Mice; Phytotherapy; Plant Extracts; Reactive Oxygen Species; Skin Aging; Ultraviolet Rays
PubMed: 31735467
DOI: 10.1016/j.jdermsci.2019.11.001