Search Results (13)

Parkinson’s disease (PD) affects movement; however, most patients with PD also develop nonmotor symptoms, such as hyposmia, sleep disorder, and depression. Dopamine levels in the brain have a critical influence on movement control, but other neurotransmitters are also involved in the progression of PD. This study analyzed the fluctuation of neurotransmitters in PC12 cells during neurogenesis and neurodegeneration by performing mass spectrometry. We found that the dopaminergic metabolism pathway of PC12 cells developed vigorously during the neuron differentiation process and that the neurotransmitters were metabolized into 3-methoxytyramine, which was released from the cells. The regulation of the intracellular and extracellular concentrations of adenosine indicated that adenine nucleotides were actively utilized in neural differentiation. Moreover, we exposed the differentiated PC12 cells to rotenone, which is a suitable material for modeling PD. The cells exposed to rotenone in the early stage of differentiation exhibited stimulated serotoninergic metabolism, and the contents of the serotoninergic neurotransmitters returned to their normal levels in the late stage of differentiation. Interestingly, the nondifferentiated cells can resist the toxicant rotenone and produce normal dopaminergic metabolites. However, when differentiated neuron cells were exposed to rotenone, they were seriously damaged, leading to a failure to produce dopaminergic neurotransmitters. In the low-dosage damage process, the amino acids that functioned as dopaminergic pathway precursors could not be absorbed by the cells, and dopamine and L-dopa were secreted and unable to be reuptaken to trigger the cell damage. Full article

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease which seriously affects public health. Gut microbiota remains a dynamic balance state in healthy individuals, and its disorder may affect health status and even results in metabolic diseases. Quercetin, a natural flavonoid, has been shown to have biological activities that can be used in the prevention and treatment of metabolic diseases. This study aimed to explore the mechanism of quercetin in alleviating T2DM based on gut microbiota. db/db mice were adopted as the model for T2DM in this study. After 10 weeks of administration, quercetin could significantly decrease the levels of body weight, fasting blood glucose (FBG), serum insulin (INS), the homeostasis model assessment of insulin resistance (HOMA-IR), monocyte chemoattractant protein-1 (MCP-1), D-lactic acid (D-LA), and lipopolysaccharide (LPS) in db/db mice. 16S rRNA gene sequencing and untargeted metabolomics analysis were performed to compare the differences of gut microbiota and metabolites among the groups. The results demonstrated that quercetin decreased the abundance of Proteobacteria, Bacteroides, Escherichia-Shigella and Escherichia_coli. Moreover, metabolomics analysis showed that the levels of L-Dopa and S-Adenosyl-L-methionine (SAM) were significantly increased, but 3-Methoxytyramine (3-MET), L-Aspartic acid, L-Glutamic acid, and Androstenedione were significantly decreased under quercetin intervention. Taken together, quercetin could exert its hypoglycemic effect, alleviate insulin resistance, repair the intestinal barrier, remodel the intestinal microbiota, and alter the metabolites of db/db mice. Full article

The use of secondary metabolites of rice to control pests has become a research hotspot, but little is known about the mechanism of rice self-resistance. In this study, metabolomics analysis was performed on two groups of rice (T1, with insect pests; T2, without pests), indicating that fatty acids, alkaloids, and phenolic acids were significantly up-regulated in T1. The up-regulated metabolites (p-value < 0.1) were enriched in linoleic acid metabolism, terpene, piperidine, and pyridine alkaloid biosynthesis, α-linolenic acid metabolism, and tryptophan metabolism. Six significantly up-regulated differential metabolites in T1 were screened out: N-trans-feruloyl-3-methoxytyramine (1), N-trans-feruloyltyramine (2), N-trans-p-coumaroyltyramine (3), N-cis-feruloyltyramine (4), N-phenylacetyl-L-glutamine (5), and benzamide (6). The insect growth inhibitory activities of these six different metabolites were determined, and the results show that compound 1 had the highest activity, which significantly inhibited the growth of Chilo suppressalis by 59.63%. Compounds 2–4 also showed a good inhibitory effect on the growth of Chilo suppressalis, while the other compounds had no significant effect. RNA-seq analyses showed that larval exposure to compound 1 up-regulated the genes that were significantly enriched in ribosome biogenesis in eukaryotes, the cell cycle, ribosomes, and other pathways. The down-regulated genes were significantly enriched in metabolic pathways, oxidative phosphorylation, the citrate cycle (TCA cycle), and other pathways. Eighteen up-regulated genes and fifteen down-regulated genes from the above significantly enriched pathways were screened out and verified by real-time quantitative PCR. The activities of detoxification enzymes (glutathione S-transferase (GST); UDP-glucuronosyltransferase (UGT); and carboxylesterase (CarE)) under larval exposure to compound 1 were measured, which indicated that the activity of GST was significantly inhibited by compound 1, while the activities of the UGT and CarE enzymes did not significantly change. As determined by UPLC-MS, the contents of compound 1 in the T1 and T2 groups were 8.55 ng/g and 0.53 ng/g, respectively, which indicated that pest insects significantly induced the synthesis of compound 1. Compound 1 may enhance rice insect resistance by inhibiting the detoxification enzyme activity and metabolism of Chilo suppressalis, as well as promoting cell proliferation to affect its normal growth and development process. The chemical–ecological mechanism of the insect resistance of rice is preliminarily clarified in this paper. Full article

Achyranthes bidentata is always salt-processed before being prescribed for treating osteoarthritis. Yet the salt-processing parameters have not been optimized, and the specific bioactive constituents responsible for the osteoarthritis effect of salt-processed A. bidentata have not been fully elucidated. In this study, a Box–Behnken experimental design was chosen for the optimization of the salt-processing parameters of A. bidentata, including stir-frying time, concentration of brine, and soak time. Meanwhile, HPLC–Q-TOF-MS was utilized to analyze the chemical profiles of various batches of raw and salt-processed A. bidentata. The anti-inflammatory potential of nine batches of both raw and salt-processed A. bidentata was assessed via a cyclooxygenase-2 (COX-2) inhibitory assay. A gray correlation analysis was conducted to correlate the peak areas of the compounds in raw and salt-processed A. bidentata with their COX-2 inhibitory effects. Finally, the optimal salt-processing conditions are as follows: soak time: 29 min; concentration of brine: 1.8%; stir-frying time: 4.4 min. Twenty-nine compounds were identified. Eight compounds were found to have a strong positive correlation with anti-inflammatory activity, as confirmed by the COX-2 inhibitory assay. Notably, this is the first report of the COX-2 inhibitory effects of sanleng acid, stachysterone D, dihydroactinidiolide, N-cis-feruloyl-3-methoxytyramine, 9,12,13-trihydroxy-10-octadecenoic acid, azelaic acid, and dehydroecdysone. Full article

This study examined whether biological sex moderates the relationship between experiences of workplace culture and urinary levels of catecholamines and their metabolites. We conducted a series of regression analyses (predictors: 3-methoxytyramine (3MT), 5-hydroxyindolacetic (5HIAA), and dopamine (DA); outcomes: employee engagement and workplace culture) in a sample of 218 participants. Compared to men, women rated workplace culture less positively (r = −0.210; p < 0.01) and had stronger positive associations with 3MT (r = 0.328; p < 0.001), DA (r = 0.376; p < 0.001), and 5HIAA (r = 0.168; p < 0.01). There was a significant moderation effect between 3MT and sex on employee engagement (b = −1.76 (SE = 0.84); p < 0.01), and 3MT had a positive significant association for men with engagement (p < 0.05); however, there was no significant association for women. Findings suggest that for women, less positive experiences with workplace culture could elevate 3MT, stimulating sympathetic nervous tone and potentially amplifying risks for negative health outcomes. Conversely, men who reported higher employee engagement had higher levels of 3MT, suggesting possible health risks associated with high levels of engagement, rather than lack of engagement. Overall, study findings suggested differential health risks based on biological sex, potentially impacting health risk policy development. Full article

The mechanism of hypertension in children remains elusive. The objective of this study was to analyze plasma metabolomics characteristics to explore the potential mechanism of hypertension in children. Serum samples from 29 control children, 38 children with normal body mass index and simple hypertension (NBp), 8 children overweight with simple hypertension (OBp), 37 children with normal body mass index and H-type hypertension (NH) and 19 children overweight with H-type hypertension (OH) were analyzed by non-targeted metabolomics. A total of 1235 differential metabolites were identified between children with hypertension and normal controls, of which 193 metabolites including various lipids were significantly expressed. Compared with the control group, 3-dehydroepiandrosterone sulfate, oleic acid and linoleic acid were up-regulated, and gamma-muricholic acid was down-regulated in the NBp group; 3-dehydroepiandrosterone sulfate, 4-acetamidobutanoate and 1-hexadecanoyl-2-octadecadienoyl-sn-glyero-3-phosphocholine were up-regulated in the OBp group, whereas adenosine and 1-myristoyl-sn-glyero-3-phosphocholine were down-regulated; in the NH group, 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine, phenol and 3-methoxytyramine were up-regulated, while pentadecanoic acid was down-regulated; in the OH group, NG,NG-dimethyl-L-arginine, 1-palmitoyl-sn-glycero-3-phosphocholine and monoethyl phthalate were up-regulated, while phloretin and glycine were down-regulated. The results showed that the children with hypertension had obvious disorders of lipid metabolism (especially in the overweight hypertension group), which led to the occurrence of hypertension. Additionally, the concentration of NO production-related NG, NG-dimethyl-L-arginine, was significantly increased, which may play an important role in H-type hypertension in children. Full article

Two different pretreatment approaches have been used for the enrichment and separation of biogenic monoamines and metabolites in plasma for high performance liquid chromatography (HPLC) determination. The first approach, based on on-line packed-fiber solid-phase extraction (PFSPE) coupled with HPLC, allows for the simultaneous detection of epinephrine (E), norepinephrine (NE), dopamine (DA), 3-methoxyl epinephrine (MN), norepinephrine (NMN), 3-methoxytyramine (3-MT), and 5-hydroxytryptamin (5-HT). Using this developed on-line PFSPE–HPLC method, the limit of detections (LODs) of the seven analytes ranged from 1 ng/mL (NMN and MN) to 2 ng/mL (NE, E, DA, 3-MT and 5-HT). The reportable ranges were 5–300 ng/mL for NE and DA, 5–100 ng/mL for E, and 5–200 ng/mL for NMN, MN, 3-MT and 5-HT. The off-line PFSPE–HPLC was employed in the second approach and could provide simultaneous detection of NE, E, DA, NMN, and MN. The linearity was verified in the range of 0.5–20 ng/mL (NE, E, and DA) and 20–250 ng/mL (NMN and MN). The LODs of the five analytes ranged from 0.2 ng/mL (NE, E, and DA) to 5 ng/mL (NMN and MN). This study verified the possibility of using nanofibers as an adsorbent in an on-line PFSPE–HPLC system for the determination of biogenic monoamines and their metabolites in human plasma. Compared with the off-line PFSPE approach, the on-line PFSPE method deserves attention mainly due to its greener character, derived from the automation of the process and high-throughput with less operators’ handling. Full article

Increased dietary phosphate intake has been associated with severity of coronary artery disease, increased carotid intima–media thickness, left ventricular hypertrophy (LVH), and increased cardiovascular mortality and morbidity in individuals with normal renal function as well as in patients suffering from chronic kidney disease. However, the underlying mechanisms are still unclear. To further elucidate the cardiovascular sequelae of long-term elevated phosphate intake, we maintained male C57BL/6 mice on a calcium, phosphate, and lactose-enriched diet (CPD, 2% Ca, 1.25% P, 20% lactose) after weaning them for 14 months and compared them with age-matched male mice fed a normal mouse diet (ND, 1.0% Ca, 0.7% P). Notably, the CPD has a balanced calcium/phosphate ratio, allowing the effects of elevated dietary phosphate intake largely independent of changes in parathyroid hormone (PTH) to be investigated. In agreement with the rationale of this experiment, mice maintained on CPD for 14 months were characterized by unchanged serum PTH but showed elevated concentrations of circulating intact fibroblast growth factor-23 (FGF23) compared with mice on ND. Cardiovascular phenotyping did not provide evidence for LVH, as evidenced by unchanged LV chamber size, normal cardiomyocyte area, lack of fibrosis, and unchanged molecular markers of hypertrophy (Bnp) between the two groups. However, intra-arterial catheterization revealed increases in systolic pressure, mean arterial pressure, and pulse pressure in mice fed the CPD. Interestingly, chronically elevated dietary phosphate intake stimulated the renin–angiotensin–aldosterone system (RAAS) as evidenced by increased urinary aldosterone in animals fed the CPD, relative to the ND controls. Furthermore, the catecholamines epinephrine, norepinephrine, and dopamine as well as the catecholamine metabolites metanephrine. normetanephrine and methoxytyramine as measured by mass spectrometry were elevated in the urine of mice on CPD, relative to mice on the ND. These changes were partially reversed by switching 14-month-old mice on CPD back to ND for 2 weeks. In conclusion, our data suggest that excess dietary phosphate induces a rise in blood pressure independent of secondary hyperparathyroidism, and that this effect may be mediated through activation of the RAAS and stimulation of the sympathetic tone. Full article

Workplace culture has been studied for impact on health risk; however, connections with robust biologic markers of health remain to be established. We examined associations between the work environment and urinary levels of catecholamines and their metabolites as biomarkers of sympathetic nervous system activity, indicative of stress. We recruited participants (n = 219; 2018–2019) from a cardiovascular risk cohort to investigate workplace culture, well-being, and stress. Participants completed seven questionnaires. Urine samples were used to measure catecholamines and their metabolites by LC/MS/MS. Pearson correlation and linear regression models were used after adjusting for demographics and creatinine. Participants reporting higher well-being had lower urinary levels of dopamine, serotonin, and 3-methoxytyramine. Participants reporting a more engaged and more positive workplace had lower levels of dopamine and 3-methoxytyramine. Reported workplace isolation was correlated with higher levels of dopamine and 3-methoxytyramine. Given correlations between catecholamines, we used 3-methoxytyramine for linear regression. In fully adjusted models, in environments with a more positive culture, levels of 3-methoxytyramine remained lower (β = −0.065 ± 0.025, p = 0.01) and indicated a positive association between workplace isolation and 3-methoxytyramine (β = 0.064 ± 0.030, p = 0.04). These findings are consistent with an important relationship between workplace environment and sympathetic nervous system activity. Full article

A novel dual-template magnetic molecularly imprinted polymer (MMIP) was synthesized to extract normetanephrine (NMN), metanephrine (MN) and 3-methoxytyramine (3-MT) from spot urine samples. As the adsorbent of dispersive solid-phase extraction (d-SPE), the MMIP was prepared using dopamine and MN as dual templates, methacrylic acid as the functional monomer, ethylene glycol dimethacrylate as the crosslinking reagent and magnetic nanoparticles as the magnetic core. NMN, MN, 3-MT and creatinine (Cr) in spot urine samples were selectively enriched by d-SPE and detected by HPLC-fluorescence detection/ultraviolet detection. The peak area (A) ratios of NMN, MN and 3-MT to Cr were used for the diagnosis of pheochromocytomas and paragangliomas (PPGLs). The results showed that the adsorption efficiencies of MMIP for target analytes were all higher than 89.0%, and the coefficient variation precisions of intra-assay and inter-assay for the analytes were within 4.9% and 6.3%, respectively. The recoveries of the analytes were from 93.2% to 112.8%. The MMIP was still functional within 14 days and could be reused at least seven times. The d-SPE and recommended solid-phase extraction (SPE) were both used to pretreat spot urine samples from 18 PPGLs patients and 22 healthy controls. The correlation coefficients of A_NMN/A_Cr and A_MN/A_Cr between d-SPE and SPE were both higher than 0.95. In addition, the areas under the receiver operator curves for spot urine A_NMN/A_Cr, A_MN/A_Cr and plasma free NMN and MN were 0.975, 0.773 and 0.990, 0.821, respectively, indicating the two methods had the similar performances. The d-SPE method took only 20 min, which was effective in clinical application. Full article

In this contribution, four new compounds synthesized from 4-hydroxycoumarin and tyramine/octopamine/norepinephrine/3-methoxytyramine are characterized spectroscopically (IR and NMR), chromatographically (UHPLC-DAD), and structurally at the B3LYP/6-311++G*(d,p) level of theory. The crystal structure of the 4-hydroxycoumarin-octopamine derivative was solved and used as a starting geometry for structural optimization. Along with the previously obtained 4-hydroxycoumarin-dopamine derivative, the intramolecular interactions governing the stability of these compounds were quantified by NBO and QTAIM analyses. Condensed Fukui functions and the HOMO-LUMO gap were calculated and correlated with the number and position of OH groups in the structures. In vitro cytotoxicity experiments were performed to elucidate the possible antitumor activity of the tested substances. For this purpose, four cell lines were selected, namely human colon cancer (HCT-116), human adenocarcinoma (HeLa), human breast cancer (MDA-MB-231), and healthy human lung fibroblast (MRC-5) lines. A significant selectivity towards colorectal carcinoma cells was observed. Molecular docking and molecular dynamics studies with carbonic anhydrase, a prognostic factor in several cancers, complemented the experimental results. The calculated MD binding energies coincided well with the experimental activity, and indicated 4-hydroxycoumarin-dopamine and 4-hydroxycoumarin-3-methoxytyramine as the most active compounds. The ecotoxicology assessment proved that the obtained compounds have a low impact on the daphnia, fish, and green algae population. Full article

This study assessed the effects of the monoamine oxidase (MAO) inhibitor deprenyl in Daphnia magna locomotor activity. The mechanisms of action of deprenyl were also determined by studying the relationship between behaviour, MAO activity and neurotransmitter levels. Modulation of the D. magna monoamine system was accomplished by 24 h exposure to two model psychotropic pharmaceuticals with antagonistic and agonistic serotonin signalling properties: 10 mg/L of 4-chloro-DL-phenylalanine (PCPA) and 1 mg/L of deprenyl, respectively. Contrasting behavioural outcomes were observed for deprenyl and PCPA reflected in decreased basal locomotor activity and enhanced habituation for the former compound and delayed habituation for the latter one. Deprenyl exposure inhibited monoamine oxidase (MAO) activity and increased the concentrations of serotonin, dopamine and the dopamine metabolite 3-methoxytyramine in whole D. magna extracts. Our findings indicate that D. magna is a sensitive and useful nonvertebrate model for assessing the effects of short-term exposure to chemicals that alter monoamine signalling changes. Full article

It has been reported that monoamine neurotransmitters can be produced by gut microbiota, and that several related metabolites of amino acids in these pathways are associated with nervous system (NVS) diseases. Herein, we focused on three pathways, namely, phenylalanine (Phe), tryptophan (Trp), and glutamic acid (Glu), and established an underivatized liquid chromatography–tandem mass spectrometry (LC-MS/MS) method for the quantification of nineteen monoamine neurotransmitters and related metabolites in the gut microbiota. The neurotransmitters and related metabolites included Phe, tyrosine (Tyr), l-dopa (Dopa), dopamine (DA), 3-methoxytyramine, Trp, hydroxytryptophan, 5-hydroxytryptamine (5-HT), 5-hydroxyindole-3-acetic acid (5-HIAA), kynurenine (KN), kynurenic acid (KYNA), melatonin, tryptamine (TA), indole-3-lactic acid (ILA), indole-3-acetic acid (IAA), indolyl-3-propionic acid (IPA), Glu, gamma-aminobutyric acid (GABA), and acetylcholine (Ach). A fluoro-phenyl bonded column was used for separation, and the mobile phase consisted of methanol:acetonitrile (1:1) and water, with 0.2% formic acid in both phases. The compounds exhibited symmetric peak shapes and sufficient sensitivity under a total analysis time of 8.5 min. The method was fully validated with acceptable linearity, accuracy, precision, matrix effect, extraction recovery, and stability. The results showed that neurotransmitters, such as Dopa, DA, 5-HT, GABA, and Ach, were present in the gut microbiota. The metabolic pathway of Trp was disordered under depression, with lower levels of 5-HT, 5-HIAA, KN, KYNA, TA, ILA, IAA, IPA, and Glu, and a higher ratio of KYNA/KN. In addition, some first-line NVS drugs, such as sertraline, imipramine, and chlorpromazine, showed regulatory potential on these pathways in the gut microbiota. Full article