The effect and mechanism of Jiao-tai-wan in the treatment of diabetes mellitus with depression based on network pharmacology and experimental analysis.

BACKGROUND: The incidence of diabetes mellitus (DM) and depression is increasing year by year around the world, bringing a serious burden to patients and their families. Jiao-tai-wan (JTW), a well-known traditional Chinese medicine (TCM), has been approved to have hypoglycemic and antidepressant effects, respectively, but whether JTW has such dual effects and its potential mechanisms is still unknown. This study is to evaluate the dual therapeutic effects of JTW on chronic restraint stress (CRS)-induced DM combined with depression mice, and to explore the underlying mechanisms through network pharmacology. METHODS: CRS was used on db/db mice for 21 days to induce depression-like behaviors, so as to obtain the DM combined with depression mouse model. Mice were treated with 0.9% saline (0.1 ml/10 g), JTW (3.2 mg/kg) and Fluoxetine (2.0 mg/kg), respectively. The effect of JTW was accessed by measuring fasting blood glucose (FBG) levels, conducting behavioral tests and observing histopathological change. The ELISA assay was used to evaluate the levels of inflammatory cytokines and the UHPLC-MS/MS method was used to determine the depression-related neurotransmitters levels in serum. The mechanism exploration of JTW against DM and depression were performed via a network pharmacological method. RESULTS: The results of blood glucose measurement showed that JTW has a therapeutic effect on db/db mice. Behavioral tests and the levels of depression-related neurotransmitters proved that JTW can effectively ameliorate depression-like symptoms in mice induced by CRS. In addition, JTW can also improve the inflammatory state and reduce the number of apoptotic cells in the hippocampus. According to network pharmacology, 28 active compounds and 484 corresponding targets of JTW, 1407 DM targets and 1842 depression targets were collected by screening the databases, and a total of 117 targets were obtained after taking the intersection. JTW plays a role in reducing blood glucose level and antidepressant mainly through active compounds such as quercetin, styrene, cinnamic acid, ethyl cinnamate, (R)-Canadine, palmatine and berberine, etc., the key targets of its therapeutic effect include INS, AKT1, IL-6, VEGF-A, TNF and so on, mainly involved in HIF-1 signal pathway, pathways in cancer, Hepatitis B, TNF signal pathway, PI3K-Akt signal pathway and MAPK signaling pathway, etc. CONCLUSION: Our experimental study showed that JTW has hypoglycemic and antidepressant effects. The possible mechanism was explored by network pharmacology, reflecting the characteristics of multi-component, multi-target and multi-pathway, which provides a theoretical basis for the experimental research and clinical application of JTW in the future.

Fast determination of 16 circulating neurotransmitters and their metabolites in plasma samples of spontaneously hypertensive rats intervened with five different Uncaria.

This study aimed to establish a sensitive, reproducible, and rapid liquid chromatography method with tandem mass spectrometry detection to perform simultaneous quantitative analysis of 16 neurotransmitters and their metabolites in rat plasma, including levodopa, dopamine, norepinephrine, epinephrine, L-tryptophan, kynurenic acid, serotonin, melatonin, choline, acetylcholine, histamine, phenylethylamine, as well as excitatory (L-glutamic acid and L-aspartic acid) and inhibitory (γ-aminobutyric acid and L-glycine) neurotransmitters. These analytes were measured by ultra-high performance chromatography coupled with triple quadrupole mass spectrometry using a hydrophilic interaction chromatographic column (ethylene-bridged hybrid amide column). The internal standards of stable isotope labeling were used to improve the reliability of the results. Our method provided high linearity for all neurotransmitters (for all coefficients measured > 0.99), with inter- and intra-day accuracy from -14.82% to 17.49% and precision was between 0.89% and 17.70%. The method was subsequently verified in an animal study, where the intervention of five different Uncarias, the traditional Chinese medicine with hypotensive effects, was applied to the spontaneously hypertensive rats (SHRs). SHRs showed dysregulated plasma kynurenic acid, acetylcholine, and norepinephrine levels, and these neuroactive analytes were significantly restored by Uncaria treatment compared with the model group (SHR group). Compared with captopril, included as a positive control for its hypotensive effect, Uncaria had more effects on perturbing the levels of plasma neurotransmitters, which might indicate Uncaria's potential in treating symptoms related to the nervous system. These results suggested that the changes in the neurotransmitters and their metabolites in plasma may be related to the pathogenesis of hypertension. It also provided valuable information about the action mechanisms of Uncaria on its hypotensive effects.

Mustard Leaf Extract Suppresses Psychological Stress in Chronic Restraint Stress-Subjected Mice by Regulation of Stress Hormone, Neurotransmitters, and Apoptosis.

Mustard leaf (Brassica juncea var. crispifolia L. H. Bailey) has been reported to have psychological properties such as anti-depressant activities. However, studies on chronic stress and depression caused by restraint have not been conducted. Therefore, this study aimed to evaluate the effects of a mustard leaf (ML) extract on chronic restraint stress (CRS) in mice. Male mice were subjected to a CRS protocol for a period of four weeks to induce stress. The results showed that the ML extract (100 and 500 mg/kg/perorally administered for four weeks) significantly decreased corticosterone levels and increased neurotransmitters levels in stressed mice. Apoptosis by CRS exposure was induced by Bcl-2 and Bax expression regulation and was suppressed by reducing caspase-3 and poly (ADP-ribose) polymerase expression after treatment with the ML extract. Our results confirmed that apoptosis was regulated by increased expression of brain-derived neurotrophic factor (BDNF). Additionally, cytokine levels were regulated by the ML extract. In conclusion, our results showed that the ML extract relieved stress effects by regulating hormones and neurotransmitters in CRS mice, BDNF expression, and apoptosis in the brain. Thus, it can be suggested that the studied ML extract is an agonist that can help relieve stress and depression.

Application of Citicoline in Neurological Disorders: A Systematic Review.

Citicoline is a chemical compound involved in the synthesis of cell membranes. It also has other, not yet explained functions. Research on the use of citicoline is conducted in neurology, ophthalmology, and psychiatry. Citicoline is widely available as a dietary supplement. It is often used to enhance cognitive functions. In our article, accessible databases were searched for articles regarding citicoline use in neurological diseases. This article has a systemic review form. After rejecting non-eligible reports, 47 remaining articles were reviewed. The review found that citicoline has been proven to be a useful compound in preventing dementia progression. It also enhances cognitive functions among healthy individuals and improves prognosis after stroke. In an animal model of nerve damage and neuropathy, citicoline stimulated regeneration and lessened pain. Among patients who underwent brain trauma, citicoline has an unclear clinical effect. Citicoline has a wide range of effects and could be an essential substance in the treatment of many neurological diseases. Its positive impact on learning and cognitive functions among the healthy population is also worth noting.

Regulating the Enteric Nervous System against Obesity in Mice by Electroacupuncture.

BACKGROUND AND OBJECTIVES: The enteric nervous system (ENS) dominates the onset of obesity and has been shown to regulate nutrient absorption and energy metabolism. METHODS AND STUDY DESIGN: This study was performed to investigate the role of electroacupuncture in regulating ENS function in obese mice. Obese mice were obtained by high-fat diet. 16S rRNA pyrosequencing, Western blotting, quantitative PCR, and neurotransmitter analysis were used for this purpose. RESULTS: Body weight, Lee index, serum lipid, leptin, and adiponectin levels, and other basic indices were significantly ameliorated after electroacupuncture intervention. The pathological ENS scores, serum neurotransmitter levels, and intestinal transit rate were markedly changed in obese mice. Moreover, electroacupuncture promoted the diversity of gut microbiota. No significant differences were observed 21 and 28 days after electroacupuncture. CONCLUSIONS: These results suggested ENS may be a new treatment approach to obesity.

Pediococcus pentosaceus B49 from human colostrum ameliorates constipation in mice.

Constipation is a prevalent and burdensome gastrointestinal (GI) disorder that seriously affects the quality of human life. This study evaluated the effects of the P. pentosaceus B49 (from human colostrum) on loperamide (Lop)-induced constipation in mice. Mice were given P. pentosaceus B49 (5 × 109 CFU or 5 × 1010 CFU) by gavage daily for 14 days. The result shows that P. pentosaceus B49 treatment relieved constipation in mice by shortening the defecation time, increasing the GI transit rate and stool production. Compared with the constipation control group, the P. pentosaceus B49-treated groups showed decreased serum levels of inhibitory neurotransmitters (vasoactive intestinal peptide and nitric oxide), increased serum levels of excitatory neurotransmitters (acetylcholinesterase, motilin, and gastrin), and elevated cecal concentration of short chain fatty acids (SCFAs). Analysis of cecal microbiota reveals that P. pentosaceus B49 was colonized in the intestine of constipated mice, and altered the cecal microbiota by increasing beneficial SCFAs-producing bacteria (i.e., Lactobacillus, Ruminococcaceae_UCG-014, and Bacteroidales_S24-7) and decreasing potential pathogenic bacteria (i.e., Staphylococcus and Helicobacter). Moreover, transcriptome analysis of the colon tissue shows that P. pentosaceus B49 partly normalized the expression of genes related to GI peristalsis (i.e., Ache, Chrm2, Slc18a3, Grp, and Vip), water and electrolyte absorption and transport (i.e., Aqp4, Aqp8, and Atp12a), while down-regulating the expression of pro-inflammatory and pro-oncogenic genes (i.e., Lbp, Lgals2, Bcl2, Bcl2l15, Gsdmc2, and Olfm4) in constipated mice. Our findings indicate that P. pentosaceus B49 effectively relieves constipation in mice and is a promising candidate for treating constipation.

[Simultaneous rapid detection of eight neurotransmitters in rat tissues,blood and urine samples by UPLC-MS/MS].

Ultra performance liquid chromatography-tandem mass spectrometry( UPLC-MS/MS) was used to establish the simultaneous determination method of eight neurotransmitters in brain,liver,kidney,adrenal gland,serum and urine,including serotonin,5-hydroxyindole acetic acid,epinephrine,norepinephrine,dopamine,glutamic acid,γ-aminobutyric acid,and acetylcholine,and then investigate the distribution characteristics of neurotransmitters in rat tissues,blood and urine. Waters ACQUITY UPLC BEH C_(18) column( 2. 1 mm×100 mm,1. 7 µm) was used,with 0. 3% formic acid solution-acetonitrile as the mobile phase for gradient elution.Multiple reaction monitoring( MRM) scanning method under positive mode by atmospheric pressure electrospray ion source( ESI) was also performed to establish the detection method of neurotransmitters for methodological research. The plasma,urine and tissues of normal rats were pre-treated including homogenization,centrifuging,and protein removal,then the 2 µL supernatant was injected for analysis. The results showed that eight kinds of neurotransmitters could be accurately determined within 7 min,with linear correlation coefficients all greater than 0. 99. This method showed high accuracy and good precision,with specificity,stability,extraction recovery and matrix effects all complying with the biological sample analysis requirements. The most abundant transmitters in the brain,liver,kidney,kidney gland,blood and urine were γ-aminobutyric acid,glutamic acid,glutamic acid,adrenaline,glutamic acid and dopamine.The method is sensitive,rapid,precise,accurate and specific,and can be used for simultaneous quantitative analysis of eight neurotransmitters in biological samples. The investigation of the distribution ratio of transmitters in rats is of important significance to disease prevention and treatment.

Electro-Acupuncture Alleviates Cisplatin-Induced Anorexia in Rats by Modulating Ghrelin and Monoamine Neurotransmitters.

Anorexia is common in patients with cancer, mostly as a side effect of chemotherapy. The effect of electro-acupuncture (EA) on ameliorating cancer-related symptoms have been studied in animal models and in clinical trials. The aim of this study was to determine optimal conditions for the application of EA to alleviate anorexia, followed by the study of molecular mechanisms affecting its therapeutics. Anorexia was induced in male Wistar rats by injecting cisplatin, which was then followed by EA treatment at CV12, the acupuncture point located in the center of the abdominal midline. Body weight and food intake were measured daily throughout the duration of the study. The levels of monoamine neurotransmitters in the plasma were quantitatively analyzed by HPLC-ECD. Gastrointestinal hormone concentrations were elucidated with ELISA kits. RT-qPCR was performed to evaluate the mRNA expression of ghrelin (GHRL), neuropeptide Y (NPY), and pro-opiomelanocortin. The expression of c-Fos in the nucleus tractus solitarii was detected using western blotting analysis. The optimal conditions of EA to alleviate anorexia in rats was determined to be 1 unit for intensity and 10 Hz for frequency. EA treatment at CV12 reduced the levels of plasma monoamine neurotransmitters 5-hydroxytryptamine, 5-hydroxyindoleacetic acid, dopamine, and norepinephrine; as well as stimulated the expression of GHRL and NPY to alleviate cisplatin-induced anorexia in rats. EA stimulation at CV12 could be used to treat cisplatin-induced anorexia in rats.

Effects of electroacupuncture on anxiety and depression in unmarried patients with polycystic ovarian syndrome: secondary analysis of a pilot randomised controlled trial.

OBJECTIVE: To evaluate the efficacy of electroacupuncture (EA) for the treatment of anxiety and depression in unmarried patients with polycystic ovarian syndrome (PCOS) by secondary analysis of a randomised controlled trial. METHODS: A prospective pilot randomised controlled trial of unmarried women with PCOS was conducted from November 2012 to March 2016. Participants were assigned to the acupuncture group (receiving EA for 16 weeks) or the control group (receiving sham acupuncture for 16 weeks), with 27 patients in each group. The pre-specified primary outcomes and all secondary outcomes, with the exception of serum levels of neurotransmitters including norepinephrine (NE), epinephrine (AD), serotonin (5-HT) and γ-aminobutyric acid (GABA), will be reported separately. Additional outcome measures selected for this secondary analysis included anxiety and depression scale scores (Zung-SAS and Zung-SDS), 36-Item Short Form (SF-36) scale scores, PCOS Quality of Life (PCOSQOL) scale scores and Chinese Quality of Life (CHQOL) scale scores. RESULTS: After the16-week intervention, an increase in serum NE and reduction in 5-HT were observed in the acupuncture group (P=0.028 and P=0.023, respectively). The serum level of GABA decreased in both groups after the interventions (both P<0.001). However, there were no significant differences between the two groups in the levels of any neurotransmitters (p>0.05). After EA treatment, SAS and SDS scores were decreased in the acupuncture group (P=0.007 and P=0.027, respectively) and were lower than those of the control group (P=0.003 and P=0.004, respectively). The SF-36 domain scores for mental health, vitality, social functioning, general health and health transition, the total CHQOL scores, and the infertility problems and body hair domains of the PCOSQOL improved significantly after EA (P<0.05). CONCLUSION: EA appears to improve symptoms of anxiety/depression and quality of life in PCOS patients and may influence serum levels of NE and 5-HT. These findings should be interpreted with caution, given the secondary nature of the outcome measures reported herein. TRIAL REGISTRATION NUMBER: NCT01812161; ChiCTR-TRC-12002529.

Low serum ω-3 and ω-6 polyunsaturated fatty acids and other metabolites are associated with poor linear growth in young children from rural Malawi.

Background: Stunting affects ∼25% of children <5 y of age and is associated with impaired cognitive and motor development and increased morbidity and mortality. The pathogenesis of stunting is poorly understood.Objective: The purpose of this study was to identify altered metabolic pathways associated with child stunting.Design: We measured 677 serum metabolites using liquid chromatography-tandem mass spectrometry in a cross-sectional study of 400 Malawian children aged 12-59 mo, of whom 62% were stunted.Results: A low height-for-age z score (HAZ) was associated with lower serum concentrations of 1) ω-3 (n-3) and ω-6 (n-6) polyunsaturated fatty acids (PUFAs), 2) sulfated neurosteroids, which play a role in brain development, 3) carnitine, a conditionally essential nutrient with an important role in the carnitine shuttle for the metabolism of fatty acids and energy production, and 4) γ-glutamyl amino acids, which represent an altered γ-glutamyl cycle of glutathione metabolism. A low HAZ was associated with significantly higher serum concentrations of 5 biomarkers related to cigarette smoke exposure.Conclusions: This metabolomics study shows a cross-sectional association between stunting and low serum ω-3 and ω-6 long-chain PUFAs, which are essential for growth and development; low sulfated neurosteroids, which play a role in brain development; low carnitine, which is essential for ß-oxidation of fatty acids; alterations in glutathione metabolism; and increased serum metabolites that are associated with secondhand tobacco smoke exposure. This trial was registered at www.controlled-trials.com as ISRCTN14597012.

Paecilomyces tenuipes extract prevents depression-like behaviors in chronic unpredictable mild stress-induced rat model via modulation of neurotransmitters.

The medicinal fungus Paecilomyces tenuipes exhibits a variety of pharmacological effects, including antidepressive effects. The chronic unpredictable mild stress (CUMS)­induced rat model has served an important role in studies involving antidepressants screening. The aim of the present study was to evaluate the antidepressant­like activity of P. tenuipes N45 aqueous extract (PTNE) in a CUMS­induced rat model of behavioral despair depression. Following 4 weeks of PTNE treatment, behavioral tests were conducted to investigate the antidepressant­like activities, and the levels of neurotransmitters and hormones in blood and hypothalamus were measured. The results demonstrated that PTNE treatment significantly increased movement in the forced running test, whereas the immobility time was reduced in the hotplate test and the forced swim test in depression­model rats. PTNE treatment was able to normalize the levels of hormones and neurotransmitters in serum and hypothalamus of CUMS rats. The data demonstrated that PTNE treatment may be a potential pharmaceutical agent in treatment­resistant depression, and the effects of PTNE may be partly mediated through normalizing the levels of neurotransmitters.

[Effect of occupational stress on neurotransmitters in petroleum workers].

OBJECTIVE: To explore the effects of occupational stress on neurotransmitters in petroleum workers. METHODS: 178 petroleum workers with the length of service ≥ 1 year were recruited to the subjects by the questionnaire of OSI-R. The levels of 5-hydroxy tryptamine (5-HT), norepinephrine (NE), neuropeptide Y (NPY) and substance P (SP) in serum were measured. The subjects were classified into 3 groups according to the scores of occupational stress. RESULTS: The levels of 5-HT NE and SP for over 15 working years were higher than those of less than 15 years (P < 0. 05). There were differences (P < 0. 05) on 5-HT, NE, NPY and SP in different occupational stress degree groups, multiple comparison showed high. occupational stress group was higher than those of low occupational stress group. Multivariate correlation analysis showed that the occupational stress and sleep quality component scores correlated positively with the 5-HT, NE and SP (P < 0. 05) and correlated inversely with NPY in petroleum workers (P < 0. 05). CONCLUSION: Occupational stress in petroleum workers is correlated with serum monoamine and neuropeptides neurotransmitters, and it may affect serum levels of monoamine and neuropeptides neurotransmitters.

Preparation of Graphene-Modified Acupuncture Needle and Its Application in Detecting Neurotransmitters.

We report a unique nanosensing platform by combining modern nanotechnology with traditional acupuncture needle to prepare graphene-modified acupuncture needle (G-AN), and using it for sensitive detection of neurotransmitters via electrochemistry. An electrochemical deposition method was employed to deposit Au nanoparticles (AuNPs) on the tip surface of the traditional acupuncture needle, while the other part of the needle was coated with insulation paste. Subsequently, the G-AN was obtained by cyclic voltammetry reduction of a graphene oxide solution on the surface of the AuNPs. To investigate the sensing property of the G-AN, pH dependence was measured by recording the open circuit potential in the various pH buffer solutions ranging from 2.0 to 10.0. What's more, the G-AN was further used for detection of dopamine (DA) with a limit of detection of 0.24 µM. This novel G-AN exhibited a good sensitivity and selectivity, and could realize direct detection of DA in human serum.

Behavioral, hormonal, and neurotransmitter reactions to stress in adult rats with a history of high IL-1ß content in the early postnatal ontogeny.

Behavioral, hormonal, and neurotransmitter reactions to foot shock were studied in adult rats treated with IL-1ß during week 3 of life. After stress, these animals differed from controls treated with saline by high levels of dopamine, serotonin, and 5-hydroxy-indolacetic acid in the hypothalamus. In contrast to controls, they developed a significant stress-induced increase of blood corticosterone level and exhibited lesser motor and exploratory activities in the open field test.

Relationship between blood- and cerebrospinal fluid-bound neurotransmitter concentrations and conditioned pain modulation in pain-free and chronic pain subjects.

UNLABELLED: Descending pain inhibition is an endogenous pain control system thought to depend partially on the activation of bulbospinal monoaminergic pathways. Deficits in descending pain inhibition have been reported in numerous human chronic pain conditions, but there is currently no consensus regarding the neurochemical correlates responsible for this deficit. The aims of this study were to 1) assess the efficacy of descending pain inhibition in pain-free and chronic pain subjects, 2) screen for changes in centrally (ie, cerebrospinal fluid) and peripherally (ie, plasma) acting monoamine concentrations, and 3) explore the relationship between descending pain inhibition and monoamine neurotransmitter concentrations. Our results clearly show a deficit in pain inhibition, along with lower plasma norepinephrine and metanephrine concentrations in chronic pain subjects, compared to pain-free subjects. No differences were found in cerebrospinal fluid neurotransmitter concentrations. Finally, our results revealed a positive relationship between blood-bound norepinephrine and metanephrine concentrations and the efficacy of descending pain inhibition. Thus, basal monoamine levels in blood were related to descending pain inhibition. This finding supports the emerging idea that individual differences in descending pain inhibition may be linked to individual differences in peripheral processes, such as monoamines release in blood, which are possibly related to cardiovascular control. PERSPECTIVES: This article presents psychophysical and neurochemical findings that indicate that the latent potential of descending pain inhibitory responses is associated with differential activity in peripheral processes governed by monoamine neurotransmitter release, bringing insights into the relationship between descending pain inhibition and cardiovascular control in humans.

Neurochemical effects of chronic administration of calcitriol in rats.

Despite accumulating data showing the various neurological actions of vitamin D (VD), its effects on brain neurochemistry are still far from fully understood. To further investigate the neurochemical influence of VD, we assessed neurotransmitter systems in the brain of rats following 6-week calcitriol (1,25-dihydroxyvitamin D) administration (50 ng/kg/day or 100 ng/kg/day). Both the two doses of calcitriol enhanced VDR protein level without affecting serum calcium and phosphate status. Rats treated with calcitriol, especially with the higher dose, exhibited elevated γ-aminobutyric acid (GABA) status. Correspondingly, the mRNA expression of glutamate decarboxylase (GAD) 67 was increased. 100 ng/kg of calcitriol administration also increased glutamate and glutamine levels in the prefrontal cortex, but did not alter glutamine synthetase (GS) expression. Additionally, calcitriol treatment promoted tyrosine hydroxylase (TH) and tryptophan hydroxylase 2 (TPH2) expression without changing dopamine and serotonin status. However, the concentrations of the metabolites of dopamine and serotonin were increased and the drug use also resulted in a significant rise of monoamine oxidase A (MAOA) expression, which might be responsible to maintain the homeostasis of dopaminergic and serotonergic neurotransmission. Collectively, the present study firstly showed the effects of calcitriol in the major neurotransmitter systems, providing new evidence for the role of VD in brain function.

The correlation between neurosteroids and neurotransmitters with liver yang rising and liver qi stagnation types of premenstrual syndrome.

BACKGROUND: To investigate neural-reproductive hormonal basis of liver yang rising (LYR), liver qi stagnation (LQS) premenstrual syndrome (PMS), and to develop standardized diagnostic criteria for PMS. METHODS: HPLC, HPLC-MC, ELISA and radioimmunoassay were used to compare levels of serum hormones, plasma neurotransmitters and neurosteroids between LYR PMS patients, LQS PMS patients and healthy controls (30 subjects in each group). RESULTS: Of the measures, all three groups exhibited no significant differences during the follicular phase. In contrast, during the luteal phase, LYR PMS testosterone levels tended to be higher than controls, while dopamine and 5-HT of the LYR PMS group were significantly higher. Conversely, γ-aminobutyric acid in the LYR PMS group was significantly lower than controls (p < 0.05). On the other hand, epinephrine and norepinephrine levels in both PMS groups were significantly higher than controls (p < 0.05), while pregnenolone and allopregnanolone of LYR and LQS groups were significantly lower than controls, with dehydroepiandrosterone (DHEA) being significantly higher than controls (p < 0.05). The ratios of DHEA/allopregnanolone and DHEA/pregnenolone of both PMS groups were significantly higher than the control group, with the LYR PMS group ratios being significantly higher than in the LQS PMS group (p < 0.05). CONCLUSION: The decrease in pregnenolone and allopregnenolone, increase in DHEA, DHEA/allopregnanolone and DHEA/pregnenolone during the luteal phase may be one of the biological bases for anger in LYR PMS patients and depression in LQS PMS patients.

[Study on drug properties of components in Euodiae Fructus based on rat stress gastric ulcer model with cold syndrome].

OBJECTIVE: To clarify drug properties of components in Euodiae Fructus. METHOD: The rat cold syndrome model was induced by cold water stress method. The content of neurotransmitters sand hormones such as DA, 5-HT, NE, AChE and 17-OHCS in serum of model rats were taken as the indexes to evaluate drug properties of components in Euodiae Fructus. RESULT: Euodiae Fructus and its components could correct or relief the content of energy metabolism and substance metabolism-related neurotransmitters sand hormones in serum of model rats with water-stressed cold syndrome. CONCLUSION: Euodiae Fructus and its components are proved to show hot property.

Ethylbenzene-induced hearing loss, neurobehavioral function, and neurotransmitter alterations in petrochemical workers.

OBJECTIVE: To estimate hearing loss, neurobehavioral function, and neurotransmitter alteration induced by ethylbenzene in petrochemical workers. METHODS: From two petrochemical plants, 246 and 307 workers exposed to both ethylbenzene and noise were recruited-290 workers exposed to noise only from a power station plant and 327 office personnel as control group, respectively. Hearing and neurobehavioral functions were evaluated. Serum neurotransmitters were also determined. RESULTS: The prevalence of hearing loss was much higher in petrochemical groups than that in power station and control groups (P < 0.05). Compared with the control group, scores of neurobehavioral function reflecting learning and memory were decreased in petrochemical workers (P < 0.05), as well as acetylcholinesterase activity. Negative correlation was shown between neurobehavioral function and acetylcholinesterase. CONCLUSIONS: Ethylbenzene exposure might be associated with hearing loss, neurobehavioral function impairment, and imbalance of neurotransmitters.

Analysis of serum metabolites for the discovery of amino acid biomarkers and the effect of galangin on cerebral ischemia.

Ischemic stroke, a devastating disease with a complex pathophysiology, is a leading cause of death and disability worldwide. In our previous study, we reported that galangin provided direct protection against ischemic injury and acted as a potential neuroprotective agent. However, its associated neuroprotective mechanism has not yet been clarified. In this paper, we explored the potential AA biomarkers in the acute phase of cerebral ischemia and the effect of galangin on those potential biomarkers. In our study, 12 AAs were quantified in rat serum and found to be impaired by middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia. Using partial least squares discriminate analysis (PLS-DA), we identified the following amino acids as potential biomarkers of cerebral ischemia: glutamic acid (Glu), homocysteine (Hcy), methionine (Met), tryptophan (Trp), aspartic acid (Asp), alanine (Ala) and tyrosine (Tyr). Moreover, four amino acids (Hcy, Met, Glu and Trp) showed significant change in galangin-treated (100 and 50 mg kg(-1)) groups compared to vehicle groups. Furthermore, we identified three pathway-related enzymes tyrosine aminotransferase (TAT), glutamine synthetase (GLUL) and monocarboxylate transporter (SLC16A10) by multiplex interactions with Glu and Hcy, which have been previously reported to be closely related to cerebral ischemia. Through an analysis of the metabolite-protein network analysis, we identified 16 proteins that were associated with two amino acids by multiple interactions with three enzymes; five of them may become potential biomarkers of galangin for acute ischemic stroke as the result of molecule docking. Our results may help develop novel strategies to explore the mechanism of cerebral ischemia, discover potential targets for drug candidates and elucidate the related regulatory signal network.