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Keywords = 2-phenethylamine (PEA)

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18 pages, 3341 KiB  
Article
In Vitro Activation of Human Adrenergic Receptors and Trace Amine-Associated Receptor 1 by Phenethylamine Analogues Present in Food Supplements
by Nicole E. T. Pinckaers, W. Matthijs Blankesteijn, Anastasiya Mircheva, Xiao Shi, Antoon Opperhuizen, Frederik-Jan van Schooten and Misha F. Vrolijk
Nutrients 2024, 16(11), 1567; https://doi.org/10.3390/nu16111567 - 22 May 2024
Cited by 5 | Viewed by 2752
Abstract
Pre-workout supplements are popular among sport athletes and overweight individuals. Phenethylamines (PEAs) and alkylamines (AA) are widely present in these supplements. Although the health effects of these analogues are not well understood yet, they are hypothesised to be agonists of adrenergic (ADR) and [...] Read more.
Pre-workout supplements are popular among sport athletes and overweight individuals. Phenethylamines (PEAs) and alkylamines (AA) are widely present in these supplements. Although the health effects of these analogues are not well understood yet, they are hypothesised to be agonists of adrenergic (ADR) and trace amine-associated receptors (TAARs). Therefore, we aimed to pharmacologically characterise these compounds by investigating their activating properties of ADRs and TAAR1 in vitro. The potency and efficacy of the selected PEAs and AAs was studied by using cell lines overexpressing human ADRα1A1B1D2a2B12 or TAAR1. Concentration–response relationships are expressed as percentages of the maximal signal obtained by the full ADR agonist adrenaline or the full TAAR1 agonist phenethylamine. Multiple PEAs activated ADRs (EC50 = 34 nM–690 µM; Emax = 8–105%). Almost all PEAs activated TAAR1 (EC50 = 1.8–92 µM; Emax = 40–104%). Our results reveal the pharmacological profile of PEAs and AAs that are often used in food supplements. Several PEAs have strong agonistic properties on multiple receptors and resemble potencies of the endogenous ligands, indicating that they might further stimulate the already activated sympathetic nervous system in exercising athletes via multiple mechanisms. The use of supplements containing one, or a combination of, PEA(s) may pose a health risk for their consumers. Full article
(This article belongs to the Special Issue Sport Supplementation for Performance and Health (Volume II))
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21 pages, 8424 KiB  
Article
Assessment of New Strategies to Improve the Performance of Antimicrobial Peptides
by Lin Wang, Hang Liu, Xinsong Li and Chen Yao
Nanomaterials 2022, 12(20), 3691; https://doi.org/10.3390/nano12203691 - 20 Oct 2022
Cited by 2 | Viewed by 1999
Abstract
In this research, we constructed a novel engineered tripeptide modified with lipoic acid (LA-RWR), followed by crosslinking of lipoic acid to form nanoparticles (c-LA-RWR). LA-RWR was also modified with phenethylamine (PEA) on the C-terminus to achieve better antibacterial activities. The as-prepared c-LA-RWR and [...] Read more.
In this research, we constructed a novel engineered tripeptide modified with lipoic acid (LA-RWR), followed by crosslinking of lipoic acid to form nanoparticles (c-LA-RWR). LA-RWR was also modified with phenethylamine (PEA) on the C-terminus to achieve better antibacterial activities. The as-prepared c-LA-RWR and LA-RWR-PEA were effective against E.coli, S.aureus, C.albicans, and methicillin-resistant Staphylococcus aureus, with minimum inhibitory concentration values ranging from 2 to 16 µg/mL, which greatly improved the performance of LA-RWR. Similar antibacterial activities were demonstrated in anti-biofilm activity; there was no matter on the biofilm that was already established or forming. Moreover, c-LA-RWR/LA-RWR-PEA remarkably induced cytoplasmic membrane depolarization and outer membrane permeabilization, resulting in varying degrees of damage to the bacterial morphology, which were consistent with the results obtained via electron microscopy. Thus, our results show that c-LA-RWR/LA-RWR-PEA exhibited excellent efficacy against a variety of microorganisms with good biosafety, providing new strategies by which to improve the performance of antimicrobial peptides. Full article
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17 pages, 1774 KiB  
Article
Aspalathus linearis (Rooibos) and Agmatine May Act Synergistically to Beneficially Modulate Intestinal Tight Junction Integrity and Inflammatory Profile
by L. Pretorius and C. Smith
Pharmaceuticals 2022, 15(9), 1097; https://doi.org/10.3390/ph15091097 - 1 Sep 2022
Cited by 12 | Viewed by 2630
Abstract
In order to promote gastrointestinal health, significant increases in the prevalence of gastrointestinal disorders should be paralleled by similar surges in therapeutics research. Nutraceutical interventions may play a significant role in patient management. The current study aimed to determine the potential of Aspalathus [...] Read more.
In order to promote gastrointestinal health, significant increases in the prevalence of gastrointestinal disorders should be paralleled by similar surges in therapeutics research. Nutraceutical interventions may play a significant role in patient management. The current study aimed to determine the potential of Aspalathus linearis (rooibos) to prevent gastrointestinal dysregulation resulting from high-dose trace-amine (TA) exposure. Considering the substantial female bias in functional gastrointestinal disorders, and the suggested phytoestrogenicity of rooibos, the study design allowed for a comparison between the effects of an ethanol extract of green rooibos and 17β-estradiol (E2). High levels of ρ-tyramine (TYR) and agmatine (AGM), but not β-phenethylamine (PEA) or tryptamine (TRP), resulted in prostaglandin E2 (PGE2) hypersecretion, increased tight-junction protein (TJP; occludin and ZO-1) secretion and (dissimilarly) disrupted the TJP cellular distribution profile. Modulating benefits of rooibos and E2 were TA-specific. Rooibos pre-treatment generally reduced IL-8 secretion across all TA conditions and prevented PGE2 hypersecretion after exposure to both TYR and AGM, but was only able to normalise TJP levels and the distribution profile in AGM-exposed cells. In contrast, E2 pre-treatment prevented only TYR-associated PGE2 hypersecretion and TJP dysregulation. Together, the data suggest that the antioxidant and anti-inflammatory effects of rooibos, rather than phytoestrogenicity, affect benefits illustrated for rooibos. Full article
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13 pages, 3769 KiB  
Article
Histamine Causes Pyroptosis of Liver by Regulating Gut-Liver Axis in Mice
by Qiaoqiao Luo, Ruoyu Shi, Yutong Liu, Libo Huang, Wei Chen and Chengtao Wang
Int. J. Mol. Sci. 2022, 23(7), 3710; https://doi.org/10.3390/ijms23073710 - 28 Mar 2022
Cited by 14 | Viewed by 2989
Abstract
Huangjiu usually caused rapid-drunkenness and components such as β-benzyl ethanol (β-be), isopentanol (Iso), histamine (His), and phenethylamine (PEA) have been reported linked with intoxication. However, the destructive effect of these components on gut microbiota and liver is unclear. In this study, we found [...] Read more.
Huangjiu usually caused rapid-drunkenness and components such as β-benzyl ethanol (β-be), isopentanol (Iso), histamine (His), and phenethylamine (PEA) have been reported linked with intoxication. However, the destructive effect of these components on gut microbiota and liver is unclear. In this study, we found oral treatment of these components, especially His, stimulated the level of oxidative stress and inflammatory cytokines in liver and serum of mice. The gut microbiota community was changed and the level of lipopolysaccharide (LPS) increased significantly. Additionally, cellular pyroptosis pathway has been assessed and correlation analysis revealed a possible relationship between gut microbiota and liver pyroptosis. We speculated oral His treatment caused the reprogramming of gut microbiota metabolism, and increased LPS modulated the gut-liver interaction, resulting in liver pyroptosis, which might cause health risks. This study provided a theoretical basis for the effect of Huangjiu, facilitating the development of therapeutic and preventive strategies for related inflammatory disorders. Full article
(This article belongs to the Special Issue Gut Microbiota and Food Ingredients)
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17 pages, 2038 KiB  
Article
2-Phenylethylamine (PEA) Ameliorates Corticosterone-Induced Depression-Like Phenotype via the BDNF/TrkB/CREB Signaling Pathway
by Young-Ju Lee, Hye Ryeong Kim, Chang Youn Lee, Sung-Ae Hyun, Moon Yi Ko, Byoung-Seok Lee, Dae Youn Hwang and Minhan Ka
Int. J. Mol. Sci. 2020, 21(23), 9103; https://doi.org/10.3390/ijms21239103 - 30 Nov 2020
Cited by 58 | Viewed by 6749
Abstract
Depression is a serious medical illness that is one of the most prevalent psychiatric disorders. Corticosterone (CORT) increases depression-like behavior, with some effects on anxiety-like behavior. 2-Phenethylamine (PEA) is a monoamine alkaloid that acts as a central nervous system stimulant in humans. Here, [...] Read more.
Depression is a serious medical illness that is one of the most prevalent psychiatric disorders. Corticosterone (CORT) increases depression-like behavior, with some effects on anxiety-like behavior. 2-Phenethylamine (PEA) is a monoamine alkaloid that acts as a central nervous system stimulant in humans. Here, we show that PEA exerts antidepressant effects by modulating the Brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB)/cAMP response element binding protein (CREB) signaling pathway in CORT-induced depression. To investigate the potential effects of PEA on CORT-induced depression, we first treated CORT (50 μM)-induced hippocampal neurons with 100 μM PEA for 24 h. We found that treatment with CORT altered dendritic spine architecture; however, treatment with PEA rescued dendritic spine formation via regulation of BDNF/TrkB/CREB signaling. Next, we used a mouse model of CORT-induced depression. Mice were treated with CORT (20 mg/kg) for 21 days, followed by assessments of a battery of depression-like behaviors. During the final four days of CORT exposure, the mice were treated with PEA (50 mg/kg). We found that CORT injection promoted depression-like behavior and significantly decreased BDNF and TrkB expression in the hippocampus. However, treatment with PEA significantly ameliorated the behavioral and biochemical changes induced by CORT. Our findings reveal that PEA exerts antidepressant effects by modulating the BDNF/TrkB/CREB signaling pathway in a mouse model of CORT-induced depression. Full article
(This article belongs to the Special Issue Molecular and Cellular Signaling on Antidepressant Mechanisms)
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20 pages, 4208 KiB  
Article
Molecular Mechanisms Underpinning Aggregation in Acidiphilium sp. C61 Isolated from Iron-Rich Pelagic Aggregates
by Qianqian Li, Rebecca E. Cooper, Carl-Eric Wegner and Kirsten Küsel
Microorganisms 2020, 8(3), 314; https://doi.org/10.3390/microorganisms8030314 - 25 Feb 2020
Cited by 6 | Viewed by 3584
Abstract
Iron-rich pelagic aggregates (iron snow) are hot spots for microbial interactions. Using iron snow isolates, we previously demonstrated that the iron-oxidizer Acidithrix sp. C25 triggers Acidiphilium sp. C61 aggregation by producing the infochemical 2-phenethylamine (PEA). Here, we showed slightly enhanced aggregate formation in [...] Read more.
Iron-rich pelagic aggregates (iron snow) are hot spots for microbial interactions. Using iron snow isolates, we previously demonstrated that the iron-oxidizer Acidithrix sp. C25 triggers Acidiphilium sp. C61 aggregation by producing the infochemical 2-phenethylamine (PEA). Here, we showed slightly enhanced aggregate formation in the presence of PEA on different Acidiphilium spp. but not other iron-snow microorganisms, including Acidocella sp. C78 and Ferrovum sp. PN-J47. Next, we sequenced the Acidiphilium sp. C61 genome to reconstruct its metabolic potential. Pangenome analyses of Acidiphilium spp. genomes revealed the core genome contained 65 gene clusters associated with aggregation, including autoaggregation, motility, and biofilm formation. Screening the Acidiphilium sp. C61 genome revealed the presence of autotransporter, flagellar, and extracellular polymeric substances (EPS) production genes. RNA-seq analyses of Acidiphilium sp. C61 incubations (+/− 10 µM PEA) indicated genes involved in energy production, respiration, and genetic processing were the most upregulated differentially expressed genes in the presence of PEA. Additionally, genes involved in flagellar basal body synthesis were highly upregulated, whereas the expression pattern of biofilm formation-related genes was inconclusive. Our data shows aggregation is a common trait among Acidiphilium spp. and PEA stimulates the central cellular metabolism, potentially advantageous in aggregates rapidly falling through the water column. Full article
(This article belongs to the Section Environmental Microbiology)
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