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International Journal of Pharmaceutics Jan 2022Drug-resistant gram-negative bacteria have emerged as a global crisis. Therefore, novel antibiotics and novel anti-infection strategies are urgently needed. Current...
PURPOSE
Drug-resistant gram-negative bacteria have emerged as a global crisis. Therefore, novel antibiotics and novel anti-infection strategies are urgently needed. Current antibiotics remain unsatisfactory due to poor targeting efficiency and poor drug penetration through the bacterial cell wall. Thus, targeted delivery of antibiotics into gram-negative bacteria should be a promising approach. Moreover, gram-negative bacteria can release lipopolysaccharide (LPS) to induce inflammatory response and septic shock, further increasing the disease burden. Hence, it is also promising to neutralize LPS while delivering antibiotics. This study aims to develop a multifunctional bacteria-targeting liposome that could enhance the delivery of antibiotics and adsorb LPS.
METHODS
A polymyxin B (PMB)-modified liposomal system (P-Lipo) was developed as novel carrier of cinnamaldehyde (CA) by using a thin-film evaporation method. Liposome morphology, size, zeta potential, stability, entrapment efficiency, and in vitro release were systematically evaluated. The bacteria-targeting effect and LPS-neutralizing capacity of P-Lipo were evaluated both in vitro and in vivo. The antibacterial effect of CA-loaded P-Lipo was assessed in Escherichia coli (E. coli) O157:H7 and Pseudomonas aeruginosa (P. aeruginosa). Ultimately, the therapeutic effect of P-CA-Lipo was investigated in E. coli O157:H7-infected mice.
RESULTS
P-Lipo was successfully synthesized and encapsulated with CA, which was well characterized. Both in vivo and in vitro experiments demonstrated that P-Lipo could efficiently target the E. coli after modification with PMB. Compared with free CA, CA-Lipo, and P-Lipo, P-CA-Lipo exhibited a significantly enhanced inhibitory effect on E. coli and P. aeruginosa. Further analysis demonstrated that P-CA-Lipo improved the bacterial uptake of CA and enhanced its antibacterial effect. It was also confirmed that P-Lipo could neutralize the LPS to avoid the inflammatory responses and inhibit the release of proinflammatory cytokines in both macrophages and mice. Finally, P-CA-Lipo inhibited E. coli-induced skin damage and death in mice and showed good biocompatibility.
CONCLUSION
The P-Lipo could target E. coli by binding with LPS and enhancing the delivery and internalization of CA. In addition, P-Lipo could adsorb free LPS synergistically, thus promoting the infection management. We believe that this strategy can provide innovative insights into antibacterial agent delivery for the treatment of persistent and severe bacterial infections.
Topics: Acrolein; Animals; Bacteria; Escherichia coli; Liposomes; Mice
PubMed: 34919996
DOI: 10.1016/j.ijpharm.2021.121356 -
International Journal of Molecular... Jul 2023Transient receptor potential ankyrin 1 (TRPA1) is a nonselective ion channel implicated in thermosensation and inflammatory pain. It has been reported that expression of...
Transient receptor potential ankyrin 1 (TRPA1) is a nonselective ion channel implicated in thermosensation and inflammatory pain. It has been reported that expression of the TRPA1 channel is induced by cigarette smoke extract. Acrolein found in cigarette smoke is highly toxic and known as an agonist of the TRPA1 channel. However, the role of TRPA1 in the cytotoxicity of acrolein remains unclear. Here, we investigated whether the TRPA1 channel is involved in the cytotoxicity of acrolein in human lung cancer A549 cells. The IC of acrolein in A549 cells was 25 μM, and acrolein toxicity increased in a concentration- and time-dependent manner. When the effect of acrolein on TRPA1 expression was examined, the expression of TRPA1 in A549 cells was increased by treatment with 50 μM acrolein for 24 h or 500 μM acrolein for 30 min. AP-1, a transcription factor, was activated in the cells treated with 50 μM acrolein for 24 h, while induction of NF-κB and HIF-1α was observed in the cells treated with 500 μM acrolein for 30 min. These results suggest that acrolein induces TRPA1 expression by activating these transcription factors. Overexpression of TRPA1 in A549 cells increased acrolein sensitivity and the level of protein-conjugated acrolein (PC-Acro), while knockdown of TRPA1 in A549 cells or treatment with a TRPA1 antagonist caused tolerance to acrolein. These findings suggest that acrolein induces the TRPA1 channel and that an increase in TRPA1 expression promotes the cytotoxicity of acrolein.
Topics: Humans; Transient Receptor Potential Channels; Acrolein; TRPA1 Cation Channel; Ankyrins; Lung Neoplasms; Cytoskeletal Proteins
PubMed: 37511605
DOI: 10.3390/ijms241411847 -
European Heart Journal Apr 2020
Topics: Acrolein; Brain; E-Cigarette Vapor; Electronic Nicotine Delivery Systems; Humans; NADPH Oxidases; Oxidative Stress
PubMed: 32211887
DOI: 10.1093/eurheartj/ehaa002 -
Experimental Neurology Jan 2020Ischemic stroke is the most common type of cerebrovascular event and is responsible for approximately 85% of all strokes in Taiwan. Neurons contain high concentrations...
BACKGROUND AND PURPOSE
Ischemic stroke is the most common type of cerebrovascular event and is responsible for approximately 85% of all strokes in Taiwan. Neurons contain high concentrations of polyamines, which are prone to various pathological states in the brain and are perturbed after cerebral ischemia. Acrolein, an α,β-unsaturated aldehyde, has been suggested as the primary culprit of neuronal damage in stroke patients. However, the mechanism by which acrolein induces neuronal damage during ischemic stroke is not clear.
METHODS
Urinary 3-hydroxypropyl mercapturic acid (3-HPMA), an acrolein-glutathione (GSH) metabolite, plasma acrolein-protein conjugates (Acr-PC) and plasma GSH levels were analyzed to correlate disease severity and prognosis of stroke patients compared with control subjects. In vivo middle cerebral artery occlusion (MCAO) animal models and an in vitro oxygen glucose deprivation (OGD) stroke model were used to investigate the mechanisms of acrolein-induced neuronal damage.
RESULTS
A deregulated acrolein metabolism, including significantly increased plasma Acr-PC levels, decreased urinary 3-HPMA levels and decreased plasma GSH levels, was found in stroke patients compared to control subjects. We further observed that acrolein was produced during ischemia resulting in brain damage in in vivo MCAO animal model. The induction of acrolein in neuronal cells during OGD occurred due to the increased expression of spermidine/spermine N1-acetyltransferase (SSAT) by NF-kB pathway activation. In addition, acrolein elicited a vicious cycling of oxidative stress resulting in neurotoxicity. Finally, N-acetylcysteine effectively prevented OGD-induced neurotoxicity by scavenging acrolein.
CONCLUSION
Overall, our current results demonstrate that acrolein is a culprit of neuronal damage through GSH depletion in stroke patients. The mechanism underlying the role of acrolein in stroke-related neuronal damage occurs through SSAT-induced polyamine oxidation by NF-kB pathway activation. These results provide a novel mechanism of neurotoxicity in stroke patients, aid in the development of neutralizing or preventive measures, and further our understanding of neural protection.
Topics: Acetyltransferases; Acrolein; Aged; Animals; Brain; Enzyme Activation; Female; Glutathione; Humans; Male; Middle Aged; Rats; Signal Transduction; Spermidine; Stroke
PubMed: 31629858
DOI: 10.1016/j.expneurol.2019.113066 -
Molecules (Basel, Switzerland) Apr 2021A wide range of analytical techniques are reported for the determination of cinnamaldehyde (CCHO) and eugenol (EOH) in plant extracts and herbal formulations either...
Simultaneous Estimation of Cinnamaldehyde and Eugenol in Essential Oils and Traditional and Ultrasound-Assisted Extracts of Different Species of Cinnamon Using a Sustainable/Green HPTLC Technique.
A wide range of analytical techniques are reported for the determination of cinnamaldehyde (CCHO) and eugenol (EOH) in plant extracts and herbal formulations either alone or in combination. Nevertheless, sustainable/green analytical techniques for the estimation of CCHO and EOH either alone or in combination are scarce in the literature. Accordingly, the present research was carried out to establish a rapid, highly sensitive, and sustainable high-performance thin-layer chromatography (HPTLC) technique for the simultaneous estimation of CCHO and EOH in the traditional and ultrasound-assisted methanolic extracts of , and and their essential oils. The simultaneous estimation of CCHO and EOH was performed through NP-18 silica gel 60 F254S HPTLC plates. The cyclohexane/ethyl acetate (90:10, ) solvent system was optimized as the mobile phase for the simultaneous estimation of CCHO and EOH. The greenness score of the HPTLC technique was predicted using AGREE software. The entire analysis was carried out at a detection wavelength of 296 nm for CCHO and EOH. The sustainable HPTLC technique was observed as linear in the range 10-2000 ng band for CCHO and EOH. The proposed technique was found to be highly sensitive, rapid, accurate, precise, and robust for the simultaneous estimation of CCHO and EOH. The content of CCHO in traditional methanolic extracts of , and was found to be 96.36, 118.49, and 114.18 mg g, respectively. However, the content of CCHO in ultrasound-assisted methanolic extracts of , and was found to be 111.57, 134.39, and 129.07 mg g, respectively. The content of CCHO in essential oils of , and was found to be 191.20, 214.24, and 202.09 mg g, respectively. The content of EOH in traditional methanolic extracts of , and was found to be 73.38, 165.41, and 109.10 mg g, respectively. However, the content of EOH in ultrasound-assisted methanolic extracts of , and was found to be 87.20, 218.09, and 121.85 mg g, respectively. The content of EOH in essential oils of , and was found to be 61.26, 79.21, and 69.02 mg g, respectively. The amounts of CCHO and EOH were found to be significantly higher in ultrasound-assisted extracts of all species compared to its traditional extraction and hence ultrasound extraction has been proposed as a superior technique for the extraction of CCHO and EOH. The AGREE analytical score of the present analytical technique was predicted as 0.75, suggesting excellent greenness profile of the proposed analytical technique. Based on all these observations and results, the proposed sustainable HPTLC technique can be successfully used for the simultaneous estimation of CCHO and EOH in different plant extracts and herbal products.
Topics: Acrolein; Chromatography, Thin Layer; Cinnamomum zeylanicum; Eugenol; Green Chemistry Technology; Least-Squares Analysis; Oils, Volatile; Plant Extracts; Reference Standards; Regression Analysis; Reproducibility of Results; Spectrophotometry, Ultraviolet; Ultrasonics
PubMed: 33916710
DOI: 10.3390/molecules26072054 -
Food & Function Jul 2022Acrolein (ACR) is frequently produced by the thermal degradation of carbohydrates and amino acids and lipid peroxidation in the thermal processing of food. Long-term...
Acrolein (ACR) is frequently produced by the thermal degradation of carbohydrates and amino acids and lipid peroxidation in the thermal processing of food. Long-term exposure to ACR can cause various chronic diseases. Here, we screened two high-temperature-resistant ACR inhibitors, cardamonin (CAR) and alpinetin (ALP), which can interconvert without any loss at 100 °C, and were obtained from Hayata (AKH). They demonstrated the best activity among the six spices investigated and could scavenge ACR generated in roasted pork by forming adducts. After three ACR adducts were prepared, namely CAR-ACR-1, CAR-ACR-2 and ALP-ACR, quantitative analysis showed that the amount of CAR-ACR-1 generated in lean roasted pork with 2% AKH addition reached the minimal inhibitory concentration against and , which was 20 times lower than that of CAR, and the higher the generation of ACR, the stronger its antibacterial activity. These results provided well-defined evidence to promote the application of AKH to ACR inhibitors in food processing.
Topics: Acrolein; Alpinia; Chalcones; Flavanones; Meat; Spices
PubMed: 35697027
DOI: 10.1039/d2fo00100d -
International Journal of Molecular... Mar 2023Acrolein, a highly reactive α,β-unsaturated aldehyde, is a compound involved in the pathogenesis of many diseases, including neurodegenerative diseases, cardiovascular... (Review)
Review
Acrolein, a highly reactive α,β-unsaturated aldehyde, is a compound involved in the pathogenesis of many diseases, including neurodegenerative diseases, cardiovascular and respiratory diseases, diabetes mellitus, and the development of cancers of various origins. In addition to environmental pollution (e.g., from car exhaust fumes) and tobacco smoke, a serious source of acrolein is our daily diet and improper thermal processing of animal and vegetable fats, carbohydrates, and amino acids. Dietary intake is one of the main routes of human exposure to acrolein, which is a major public health concern. This review focuses on the molecular mechanisms of acrolein activity in the context of its involvement in the pathogenesis of diseases related to the digestive system, including diabetes, alcoholic liver disease, and intestinal cancer.
Topics: Animals; Humans; Aldehydes; Acrolein; Digestive System Diseases; Diet; Diabetes Mellitus
PubMed: 37047550
DOI: 10.3390/ijms24076579 -
European Journal of Medicinal Chemistry Sep 2019Cancer is known as a leading cause of death worldwide. In the last two decades, the incidence of cancer has been dramatically increased mostly due to lifestyle changes.... (Review)
Review
Cancer is known as a leading cause of death worldwide. In the last two decades, the incidence of cancer has been dramatically increased mostly due to lifestyle changes. The importance of this issue has attracted further attention to discover novel therapies to prevent and treat cancers. According to previous studies, drugs used to treat cancer have shown significant limitations. Therefore, the role of herbal medicines alone or in combination with chemotherapy drugs has been extensively studied in cancer treatment. Cinnamon is a natural component showing a wide range of pharmacological functions including anti-oxidant, anti-microbial and anti-cancer activities. Impaired apoptosis plays critical roles in the initiation and progression of cancer. Increasing evidence indicates that cinnamon, as a therapeutic agent, has anti-cancer effects via affecting numerous apoptosis-related pathways in cancer cells. Here, we highlighted anticancer properties of cinnamon, particularly through targeting apoptosis-related mechanisms.
Topics: Acrolein; Animals; Antineoplastic Agents; Apoptosis; Benzoates; Cell Line, Tumor; Cinnamomum zeylanicum; Eugenol; Humans; Plant Extracts
PubMed: 31195168
DOI: 10.1016/j.ejmech.2019.05.067 -
Food Additives & Contaminants. Part A,... Jan 2020Carbonyl compounds and furan derivatives may form adducts with DNA and cause oxidative stress to human cells, which establishes the carcinogenic potential of these...
Carbonyl compounds and furan derivatives may form adducts with DNA and cause oxidative stress to human cells, which establishes the carcinogenic potential of these compounds. The occurrence of these compounds may vary according to the processing characteristics of the beer. The objective of this study was, for the first time, to investigate the free forms of target carbonyl compounds [acetaldehyde, acrolein, ethyl carbamate (EC) and formaldehyde] and furan derivatives [furfural and furfuryl alcohol (FA)] during the brewing stages of ale and lager craft beers. Samples were evaluated using headspace-solid phase microextraction and gas chromatography with mass spectrometric detection in selected ion monitoring mode (HS-SPME-GC/MS-SIM). Acetaldehyde, acrolein, formaldehyde and furfuryl alcohol were found in all brewing stages of both beer types, while EC and furfural concentrations were below the LOD and LOQ of the method (0.1 and 0.01 µg L, respectively). Boiling and fermentation of ale brewing seem to be important steps for the formation of acrolein and acetaldehyde, respectively, while boiling resulted in an increase of FA in both types of beer. Conversely, pasteurisation and maturation reduced the levels of these compounds in both types of beer. An increase in concentration of acrolein has not been verified in lager brew probably due to the difference in boiling time between these two types of beer (60 and 90 min for ale and lager, respectively).
Topics: Acetaldehyde; Acrolein; Beer; Fermentation; Food Analysis; Food Contamination; Formaldehyde; Furans; Humans; Urethane
PubMed: 31622171
DOI: 10.1080/19440049.2019.1675911 -
Food & Function Sep 2020Acrolein is a notorious aldehyde with hazardous impacts on humans. γ-Aminobutyric acid (GABA) is a functional amino acid present widely in foods. This study aimed at...
Acrolein is a notorious aldehyde with hazardous impacts on humans. γ-Aminobutyric acid (GABA) is a functional amino acid present widely in foods. This study aimed at investigating the protective mechanism of GABA against acrolein. In simulated physiological and thermal processing models, GABA effectively scavenged acrolein by adduct formation. The cytotoxicity of the formed adduct was evaluated in human bronchial epithelial cell line HBE and normal colonic epithelial cell line NCM460. It tremendously decreased acrolein toxicity and exerted protective effects by ROS reduction. Apoptotic staining and signaling analysis showed that it also interfered with apoptosis via extrinsic and intrinsic pathways. Our findings provide the basic knowledge that GABA is an effective acrolein scavenger and it has potential detoxifying capacity for both exogenous and endogenous acrolein sourced cellular damage.
Topics: Acrolein; Apoptosis; Cell Line; Cell Survival; Free Radical Scavengers; Humans; Oxidative Stress; Reactive Oxygen Species; gamma-Aminobutyric Acid
PubMed: 32793937
DOI: 10.1039/c9fo02518a