Is There a Dysregulation of Backdoor Pathway of Androgen Synthesis in Autistic Disorders?

Background: Several time associations of androgens and autism were implied. Therefore, we hypothesized that a dysregulation of backdoor pathway during puberty might be one factor affecting dysregulated androgens in autism. Material & Methods: Urine samples were collected from 20 boys originally diagnosed with Asperger syndrome, 21 boys with Kanner syndrome, 8 with Atypical autism as well as 5 girls with Asperger syndrome, 10 girls with Kanner Syndrome and one with Atypical autism and a control group for gas chromatography mass spectrometry based steroid hormone analysis. As Etiocholanolone (E) originates almost exclusively from the classic pathway and Androsterone (A) may be derived additionally from the backdoor pathway analyses of A/E ratios in affected autistic boys and girls were used to identify a potential dysregulation of backdoor pathway of androgen synthesis. Results: In Kanner boys Androsterone and Eticholanolone showed increased concentrations of around fifty percent (p < 0.01). In addition, in boyswith Asperger Syndrome an increase of Androsterone (p < 0.01) and Eticholanolone (p < 0.01) was detected.

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Testosterone/Epitestosterone Ratios—Further Hints to Explain Hyperandrogenemia in Children with Autism

Diseases ◽

10.3390/diseases9010013 ◽

2021 ◽

Vol 9 (1) ◽

pp. 13

Author(s):

Benedikt Gasser ◽

Johann Kurz ◽

Markus Mohaupt

Keyword(s):

Competitive Inhibition ◽

Incidental Finding ◽

Steroid Hormone ◽

Children With Autism ◽

Small Sample ◽

Gas Chromatography Mass Spectrometry ◽

Typical Development ◽

Androgen Synthesis ◽

Significant Difference ◽

Enzymatic Cascades

Background: Epitestosterone [E] has for a long time been considered as a biologically inactive androgen. However, recently a distinct antiandrogenic activity of this naturally occurring endogenous epimer of Testosterone has been demonstrated. Especially the ratios of testosterone/epitestosterone (T/E) seem to be key as inhibition of epitestosterone on androgen activity was postulated. As in autism, a higher androgen activity was implied. We, therefore, suggested higher levels of T/E ratios of children with autism versus children with typical development. Methods: Urine probes of 22 girls with autism (BMI 18.7 ± 4.3; average age 12.3 ± 3.8 years) and a sample of 51 controls (BMI 17.0 ± 2.6; average age 11.9 ± 4 years), as well as 61 boys with autism (BMI 17.04 ± 2. average age 11.9 ± 2.5 years) and 61 control boys (BMI 17.0 ± 2.6; average age 11.1 ± 3.0 years), were analyzed with gas chromatography mass spectrometry. RESULTS: The average T/E ratio of all boys with autism was 2.5 ± 1.8 versus 2.4 ± 1.3 in boys with typical development, respectively. No significant difference between boys with autism versus boys with typical development could be detected (p = 0.977). In girls with autism, the average T/E ratio was 1.4 ± 0.9 versus 2.0 ± 1.4 in girls with typical development, whereby a significant difference could be detected (p = 0.0285). Further, polynomial analysis of the third degree were conducted, showing a dependence from age with reasonable coefficients of determination (0.075 < R2 < 0.22, all samples). Discussion: As encompassing steroid hormone analysis are expensive and work-intensive, we hoped to find an easily applicable biomarker to support diagnostics in autism. However, as a relatively small sample of only 22 girls with autism were analyzed and menstrual cycle and pubertal status were only partly controllable through the matching of BMI and age, the question arises if it was an incidental finding. Nevertheless, one suggestion might be that epitestosterone has the effect of a competitive inhibition on the androgen receptor, which would probably help to explain the higher prevalence of autism in boys as compared to girls. Presumably, as no significant difference was detected in boys, this effect might not be as relevant from a steroid hormone perspective, and other effects such as altered 17/20-hydroxylase activity as previously shown in boys and girls with autism seem to have more relevance. Analysis of larger samples, including plenty of metabolites and enzymatic cascades, as well as the role of backdoor pathway activity of androgen synthesis of girls with autism, are demanded in order to validate current findings of altered steroid hormones in autism.

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Testosterone-dependent changes in neurons of hypothalamic arcuate nucleus and reversibility of these changes by modeled male hypogonadism

ZHurnal «Patologicheskaia fiziologiia i eksperimental`naia terapiia» ◽

10.25557/igpp.2017.4.8519 ◽

2017 ◽

pp. 21-30

Author(s):

А.В. Дробленков ◽

Л.Г. Прошина ◽

Ю.Н. Юхлина ◽

А.А. Байрамов ◽

П.Д. Шабанов ◽

...

Keyword(s):

Replacement Therapy ◽

Nerve Cell ◽

Arcuate Nucleus ◽

Degenerative Changes ◽

Control Group ◽

Male Hypogonadism ◽

Nissl Staining ◽

Neuron Body ◽

Androgen Synthesis ◽

Reactive Changes

Актуальность. Значение недостаточности тестостерона для структурного гомеостазиса нейронов, регулирующих выработку гонадотропин-рилизинг гормона (ГнРГ) и синтезирующих данный гормон, мало изучены. Цель. Установить реактивные изменения, количество рецепторов к андрогенам (АР) и особенности их распределения в нейронах медиального аркуатного ядра гипоталамуса (МАЯ) при экспериментальном гипогонадизме, а также обратимость этих изменений после восстановительной терапии тестостероном. Методы. У самцов крыс Вистар (16 особей) моделировали гипогонадизм путем удаления одной гонады на 2-3 день постнатальной жизни и исследовали гистологические срезы каудальной части МАЯ у молодых животных (4 мес.) при отсутствии и осуществлении заместительной терапии. Контрольную группу составляли интактные самцы аналогичного возраста (8 особей). В середине левосторонней части МАЯ на площади 0,01 мм определяли реактивные изменения клеток и площадь тел малоизмененных нейронов (после окрашивания срезов методом Ниссля), а также число и долю тел нервных клеток, различавшихся по степени экспрессии АР. Результаты. Установлено, что нейроны МАЯ содержат большое количество АР, распределенных в различных частях их тела. При гипогонадизме происходит перераспределение АР и снижение степени их экспрессии (количества). Сгущение АР в области оболочки ядра и плазмолеммы, образование конгломератов в ядре и цитоплазме было характерно для нейронов с умеренной экспрессией. В цитоплазме и в области плазматической мембраны рецепторы отсутствовали у клеток со слабой и очень низкой экспрессией. Снижение степени экспрессии АР при гипогонадизме сопряжено с уменьшением площади тела и гибелью части нейронов. Заключение. Выявленные дегенеративные тестостерон-зависимые изменения нейронов МАЯ, которые синтезируют ГнРГ или пептиды, влияющие на его выработку, могут обусловить уменьшение высвобождения гонадолиберина, вторичное снижение синтеза андрогенов и реализацию морфофункциональных проявлений его вторичного дефицита. Заместительная терапия частично компенсирует дегенеративные изменения нейронов, восстанавливает интенсивность экспрессии АР, однако не влияет на процесс гибели нервных клеток. Background. Importance of testosterone deficiency for structural homeostasis of the neurons regulating production of gonadotropin-releasing hormone (GnRH) and synthesizing this hormone is insufficiently understood. Aim. To determine reactive changes, quantity of androgens receptors (AR), and features of their distribution in neurons of hypothalamic medial arcuate nucleus (MAN) in experimental hypogonadism and reversibility of these changes by restorative therapy with testosterone. Methods. Hypogonadism was modeled in 16 Wistar rats by removing one gonad on postnatal days 2-3, and histological sections of caudal MAN were examined in young, 4-month old animals with and without a replacement therapy. The control group consisted of 8 age-matched intact males. Cell reactive changes, areas of slightly changed neuron bodies (Nissl staining of sections), and the number and proportion of nerve cell bodies differing in the degree of AR expression were determined in the middle left-sided part of MAN, on an area of 0.01 mm. Results. MAN neurons contained a large quantity of AR distributed in different parts of the neuron body. In hypogonadism, AR redistributed and their expression (quantity) decreased. Condensation of AR in the region of nucleo- and plasmolemma and formation of conglomerates in the nucleus and cytoplasm were characteristic of neurons with moderate expression. In the regions of cytoplasm and plasma membrane, the receptors were absent in cells with low and very low expression. The reduced AR expression in hypogonadism was associated with a decreased neuron body area and death of a part of neurons. Conclusions. The identified degenerative changes in the testosterone-dependent neuronal MAN that synthesize GnRH or peptides affecting the GnRH production may decrease the release of GnRH, cause a secondary decrease in the androgen synthesis, and mediate morphological and functional manifestations of GnRH secondary deficit. The replacement therapy partially compensated for degenerative changes in neurons and restored the intensity of AR expression, however, it did not influence the process of nerve cell death.

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Gut Microbiome and Metabolome Profiles Associated with High-Fat Diet in Mice

Metabolites ◽

10.3390/metabo11080482 ◽

2021 ◽

Vol 11 (8) ◽

pp. 482

Author(s):

Jae-Kwon Jo ◽

Seung-Ho Seo ◽

Seong-Eun Park ◽

Hyun-Woo Kim ◽

Eun-Ju Kim ◽

...

Keyword(s):

Gut Microbiota ◽

Relative Abundance ◽

High Fat Diet ◽

Amplicon Sequencing ◽

Gas Chromatography Mass Spectrometry ◽

Control Group ◽

Rrna Gene ◽

High Fat ◽

Underlying Mechanisms ◽

Insight Into

Obesity can be caused by microbes producing metabolites; it is thus important to determine the correlation between gut microbes and metabolites. This study aimed to identify gut microbiota-metabolomic signatures that change with a high-fat diet and understand the underlying mechanisms. To investigate the profiles of the gut microbiota and metabolites that changed after a 60% fat diet for 8 weeks, 16S rRNA gene amplicon sequencing and gas chromatography-mass spectrometry (GC-MS)-based metabolomic analyses were performed. Mice belonging to the HFD group showed a significant decrease in the relative abundance of Bacteroidetes but an increase in the relative abundance of Firmicutes compared to the control group. The relative abundance of Firmicutes, such as Lactococcus, Blautia, Lachnoclostridium, Oscillibacter, Ruminiclostridium, Harryflintia, Lactobacillus, Oscillospira, and Erysipelatoclostridium, was significantly higher in the HFD group than in the control group. The increased relative abundance of Firmicutes in the HFD group was positively correlated with fecal ribose, hypoxanthine, fructose, glycolic acid, ornithine, serum inositol, tyrosine, and glycine. Metabolic pathways affected by a high fat diet on serum were involved in aminoacyl-tRNA biosynthesis, glycine, serine and threonine metabolism, cysteine and methionine metabolism, glyoxylate and dicarboxylate metabolism, and phenylalanine, tyrosine, and trypto-phan biosynthesis. This study provides insight into the dysbiosis of gut microbiota and metabolites altered by HFD and may help to understand the mechanisms underlying obesity mediated by gut microbiota.

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Metabolomics Analysis Reveals Potential Mechanisms in Bupleurum L. (Apiaceae) Induced by Three Levels of Nitrogen Fertilization

Agronomy ◽

10.3390/agronomy11112291 ◽

2021 ◽

Vol 11 (11) ◽

pp. 2291

Author(s):

Jialin Sun ◽

Weinan Li ◽

Ye Zhang ◽

Yun Guo ◽

Zejia Duan ◽

...

Keyword(s):

Nitrogen Fertilization ◽

Total Content ◽

Nitrogen Level ◽

Gas Chromatography Mass Spectrometry ◽

Control Group ◽

High Nitrogen ◽

Yield And Quality ◽

High Nitrogen Level ◽

The Impact ◽

The Relationship

Bupleurum (Apiaceae) is widely used in traditional Chinese medicine to treat inflammatory and infectious diseases. Although roots are the only used parts in China, other countries use the whole plant. The yield and quality of Bupleurum depend mainly on fertilizers, especially nitrogen. The current study aimed to assess the relationship between the nitrogen fertilization level and the quality and metabolomic response of different parts (flowers, main shoots, lateral shoots and roots) of Bupleurum to three nitrogen fertilization levels (control group: 0 kg·ha−1; low-nitrogen group: 55 kg·ha−1; high-nitrogen group: 110 kg·ha−1). The results showed that a high nitrogen level increases Bupleurum yield and quality parameters only in aerial parts, especially flowers, but has no significant effect on roots. The HPLC method was exploited for simultaneous quantification of three saikosaponins (A, C and D), which are the main bioactive components in the plant. It was found that the total content of saikosaponins decreased with high nitrogen fertilization in roots but significantly increased in flowers. Moreover, nitrogen fertilizer promoted the content of saikosaponin A but inhibited saikosaponins C and saikosaponins D in most parts of the plant. To study the response of primary metabolites, we adopted gas chromatography–mass spectrometry (GC−MS) analysis; 84 metabolites were identified that were mostly up-regulated with a high nitrogen level in flowers but down-regulated in roots. Four differential metabolites—D-fructose, lactose, ether and glycerol—were recognized as key metabolites in Bupleurum under nitrogen fertilization. Meanwhile, The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment results explained that the impact of nitrogen fertilization on Bupleurum was attributed to the C-metabolism, N-metabolism, and lipids metabolism. This research put forward new insights into potential mechanisms and the relationship between the quality and yield of Bupleurum and nitrogen fertilization.

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Urinary Volatomic Expression Pattern: Paving the Way for Identification of Potential Candidate Biosignatures for Lung Cancer

Metabolites ◽

10.3390/metabo12010036 ◽

2022 ◽

Vol 12 (1) ◽

pp. 36

Author(s):

Khushman Taunk ◽

Priscilla Porto-Figueira ◽

Jorge A. M. Pereira ◽

Ravindra Taware ◽

Nattane Luíza da Costa ◽

...

Keyword(s):

Lung Cancer ◽

Fatty Acid Biosynthesis ◽

Solid Phase ◽

Partial Least Square ◽

Least Square ◽

Gas Chromatography Mass Spectrometry ◽

Support Vector ◽

Control Group ◽

Potential Candidate ◽

Metabolic Pathway Analysis

The urinary volatomic profiling of Indian cohorts composed of 28 lung cancer (LC) patients and 27 healthy subjects (control group, CTRL) was established using headspace solid phase microextraction technique combined with gas chromatography mass spectrometry methodology as a powerful approach to identify urinary volatile organic metabolites (uVOMs) to discriminate among LC patients from CTRL. Overall, 147 VOMs of several chemistries were identified in the intervention groups—including naphthalene derivatives, phenols, and organosulphurs—augmented in the LC group. In contrast, benzene and terpenic derivatives were found to be more prevalent in the CTRL group. The volatomic data obtained were processed using advanced statistical analysis, namely partial least square discriminative analysis (PLS-DA), support vector machine (SVM), random forest (RF), and multilayer perceptron (MLP) methods. This resulted in the identification of nine uVOMs with a higher potential to discriminate LC patients from CTRL subjects. These were furan, o-cymene, furfural, linalool oxide, viridiflorene, 2-bromo-phenol, tricyclazole, 4-methyl-phenol, and 1-(4-hydroxy-3,5-di-tert-butylphenyl)-2-methyl-3-morpholinopropan-1-one. The metabolic pathway analysis of the data obtained identified several altered biochemical pathways in LC mainly affecting glycolysis/gluconeogenesis, pyruvate metabolism, and fatty acid biosynthesis. Moreover, acetate and octanoic, decanoic, and dodecanoic fatty acids were identified as the key metabolites responsible for such deregulation. Furthermore, studies involving larger cohorts of LC patients would allow us to consolidate the data obtained and challenge the potential of the uVOMs as candidate biomarkers for LC.

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Steroid hormone profiles and molecular diagnostic tools in pediatric patients with non-CAH primary adrenal insufficiency

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgac016 ◽

2022 ◽

Author(s):

Tuba Seven Menevse ◽

Yasemin Kendir Demirkol ◽

Busra Gurpinar Tosun ◽

Elvan Bayramoglu ◽

Melek Yildiz ◽

...

Keyword(s):

Adrenal Insufficiency ◽

Molecular Diagnosis ◽

High Throughput Sequencing ◽

Steroid Hormone ◽

Genetic Diagnosis ◽

Molecular Diagnostic ◽

Diagnostic Tools ◽

Unknown Etiology ◽

Control Group ◽

Primary Adrenal Insufficiency

Abstract Background There is a significant challenge of attributing specific diagnoses to patients with primary adrenal insufficiency of unknown etiology other than congenital adrenal hyperplasia (non-CAH PAI). Specific diagnoses per se may guide personalized treatment or may illuminate pathophysiology. Objective Investigation of the efficacy of steroid hormone profiles and high-throughput sequencing methods in establishing the etiology in non-CAH PAI of unknown origin. Design Paediatric patients with non-CAH PAI whose etiology could not be established by clinical and biochemical characteristics were enrolled. Genetic analysis was performed using targetedgene panel sequencing (TPS) and whole-exome sequencing (WES). Plasma adrenal steroids were quantified by liquid chromatography-mass spectrometry and compared to that of controls. Setting Eighteen pediatric endocrinology clinics. Patients Forty-one patients (17 females, median age: 3 months, range: 0-8 years) with non-CAH PAI of unknown etiology. Results A genetic diagnosis was obtained in 29 (70.7%) patients by TPS. Further molecular diagnosis could not be achieved by WES. Compared to healthy control group, patients showed lower steroid concentrations, most significantly in cortisone, cortisol, and corticosterone (p<0.0001, area under the ROC curve: 0.96, 0.88, 0.87, respectively). Plasma cortisol<4 ng/mL, cortisone<11 ng/mL, and corticosterone<0.11 ng/mL had >95% specificity to ensure the diagnosis of non-CAH PAI of unknown etiology. Conclusion Steroid hormone profiles are highly sensitive for the diagnosis of non-CAH PAI of unknown etiology, while they are unlikely to point out a specific molecular diagnosis. TPS is an optimal approach in the molecular diagnosis of these patients with high efficacy, while little additional benefit is expected from WES.

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Abstract WP259: Metabolomic Analysis of Ischemic Brain Tissue to Explore Specific Metabolic Pathway Assosiated With Cerebral Ischemia

Stroke ◽

10.1161/str.47.suppl_1.wp259 ◽

2016 ◽

Vol 47 (suppl_1) ◽

Author(s):

Yusuke Yamamoto ◽

Kohkichi Hosoda ◽

Yasuhiro Irino ◽

Jun Tanaka ◽

Taichiro Imahori ◽

...

Keyword(s):

Cerebral Ischemia ◽

Western Blot ◽

Brain Tissue ◽

Water Soluble ◽

Gas Chromatography Mass Spectrometry ◽

Control Group ◽

Acute Ischemia ◽

Rt Pcr ◽

Ischemic Lesion ◽

Ischemic Brain

Objectives: We investigated metabolic profiles of brain tissue in middle cerebral artery occlusion (MCAO) model of rats to explore the specific changes associated with acute ischemia. Methods: Focal cerebral ischemia was induced in rats using filament occlusion of the MCA. Tissue samples from the ischemic lesion were collected before and after ischemia(0, 30, 60, 120min, n=7-10). Sham operated rats were treated in the same way except MCAO (n=10). Water-soluble metabolites were extracted and analyzed using gas-chromatography/mass-spectrometry(GS/MS). The obtained data were analyzed by multivariate statistics to explore metabolic pathways associated with ischemia. The associated metabolic enzymes were investigated with RT-PCR and Western blot. Results: About ninety metabolites were identified by GC/MS. Principal component analysis and heatmap demonstrated clear separation between ischemia and control group (Figures). The most significant changes were decrease of fructose-6-phosphate and ribulose-5-phosphate, increase of hydroxybutyrate, and increase of GABA with time. These results suggested acceleration of pentose phosphate pathway to increase NADPH, upregulation of keton metabolism and neuroprotection by GABA. RT-PCR and Western blot did not indicate significant changes of transcription and protein level of the enzymes involved in these pathways and suggested changes of the enzyme activity by modification after transcription or translation such as phosphorylation. Conclusions: These results suggested the presence of neuroprotective metabolic change in the ischemic brain.

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MO005HIGH LEVELS OF FIVE SPECIFIC FECAL METABOLITES IN IGA NEPHROPATHY PATIENTS SUPPORT THE HYPOTHESIS OF THE INTESTINAL-RENAL AXIS CONNECTION

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa140.mo005 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Claudia Curci ◽

Fabio Sallustio ◽

Nada Chaoul ◽

Angela Picerno ◽

Gabriella Lauriero ◽

...

Keyword(s):

B Cells ◽

Iga Nephropathy ◽

Solid Phase ◽

Serum Levels ◽

Intestinal Lumen ◽

Gas Chromatography Mass Spectrometry ◽

Control Group ◽

Intestinal Immunity ◽

Adaptive Immune Cells

Abstract Background and Aims The IgA nephropathy (IgAN) is the most frequent primitive glomerulonephritis. In the last years, the role of mucosal immunity in IgAN, together with that of the gut microbiota in the activation of innate and adaptive immune cells, has gained importance. Particularly interesting is the role of the microbiota and intestinal immunity in IgAN. BAFF and APRIL can be produced by the intestinal epithelium, in response to signals triggered by TLRs once activated by the commensal bacteria present in the intestinal lumen, representing the link between microbiota and intestinal immunity. To date, even if hypothesized, this relationship in IgAN patients has not been investigated. Here, we studied the intestinal-renal axis connections analyzing levels of BAFF, April and intestinal-activated B cells in IgAN patients. Method Serum and fecal samples were collected from 44 IgAN patients, 22 non-IgA glomerulonephritides (controls) and 22 healthy subjects (HS) with similar clinical features. BAFF and APRIL serum levels were measured by ELISA assay. Metabolomic analysis of fecal microbiome was performed using Biochrom 30 series amino acid analyzer and gas-chromatography mass spectrometry/solid-phase microextraction (GC-MS/SPME) analysis. B cell subsets were investigated by FACS. Results IgAN patients had increased serum levels of BAFF cytokine compared to the control group of patients with non-IgA glomerulonephritis and compared with HS (p<0.0001and p=0.012, respectively). We found that serum BAFF levels positively correlated with the levels of 24h-proteinuria in IgAN patients (r2 = 0.2269, p <0.001). We correlated serum BAFF levels with fecal concentration of 5 different metabolites of 30 IgAN patients, which were previously investigated for the fecal microbiota. These organic compounds had been found at significantly higher levels in the feces of IgAN patients compared to HS. Serum BAFF levels positively correlated with the levels of fecal metabolites: 4-(1,1,3,3-tetramethylbutyl) phenol (r2 = 0.2882, p = 0.0027), p-tert-butyl-phenol (r2 = 0.386, p = 0.0003), methyl neopentyl phthalic acid (r2 = 0.3491, p =0.0007), hexadecyl ester benzoic acid (r2 = 0.2832, p =0.003) and furanone A (r2 = 0.1743, p = 0.024). Serum levels of APRIL were significantly increased in IgAN patients respect to control groups (4.49 ± 0.54 vs 2.27 ± 1 ng/ml, p=0.0014). We found a correlation between APRIL and serum creatinine (r2 = 0.159, p =0.04) and eGFR (r2 = 0.2395, p =0.0082), while no correlation was found between APRIL and fecal metabolite levels in IgAN patients. In addition, we found that subjects with IgAN have a significantly higher proportion of circulating Bregs, Memory B cells and IgA secreting-plasmablasts activated at the intestinal level (CCR9+INTB7+) compared to HS. Conclusion The results of our study showed for the first time an important correlation of serum levels of BAFF with intestinal microbiota in patients with IgAN, confirming the hypothesis of the pathogenic role of intestinal mucosal hyperresponsiveness in the IgAN patients. The intestinal-renal axis plays a crucial role in Berger's glomerulonephritis, whose complex pathogenesis may contribute several factors as genetics, pathogens and food.

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Therapeutic Effect and Metabolic Mechanism of A Selenium-Polysaccharide from Ziyang Green Tea on Chronic Fatigue Syndrome

Polymers ◽

10.3390/polym10111269 ◽

2018 ◽

Vol 10 (11) ◽

pp. 1269 ◽

Cited By ~ 1

Author(s):

Changzhuan Shao ◽

Jing Song ◽

Shanguang Zhao ◽

Hongke Jiang ◽

Baoping Wang ◽

...

Keyword(s):

Therapeutic Effect ◽

Green Tea ◽

Metabolic Pathways ◽

Steroid Hormone ◽

Chronic Fatigue ◽

Gas Chromatography Mass Spectrometry ◽

Urine Metabolites ◽

Steroid Hormone Biosynthesis ◽

Hormone Biosynthesis ◽

Metabolic Mechanism

Ziyang green tea was considered a medicine food homology plant to improve chronic fatigue Ssyndrome (CFS) in China. The aim of this research was to study the therapeutic effect of selenium-polysaccharides (Se-TP) from Ziyang green tea on CFS and explore its metabolic mechanism. A CFS-rats model was established in the present research and Se-TP was administrated to evaluate the therapeutic effect on CFS. Some serum metabolites including blood urea nitrogen (BUN), blood lactate acid (BLA), corticosterone (CORT), and aldosterone (ALD) were checked. Urine metabolites were analyzed via gas chromatography-mass spectrometry (GC-MS). Multivariate statistical analysis was also used to check the data. The results selected biomarkers that were entered into the MetPA database to analyze their corresponding metabolic pathways. The results demonstrated that Se-TP markedly improved the level of BUN and CORT in CFS rats. A total of eight differential metabolites were detected in GC-MS analysis, which were benzoic acid, itaconic acid, glutaric acid, 4-acetamidobutyric acid, creatine, 2-hydroxy-3-isopropylbutanedioic acid, l-dopa, and 21-hydroxypregnenolone. These differential metabolites were entered into the MetPA database to search for the corresponding metabolic pathways and three related metabolic pathways were screened out. The first pathway was steroid hormone biosynthesis. The second was tyrosine metabolism, and the third was arginine-proline metabolism. The 21-hydroxypregnenolone level of rats in the CFS group markedly increased after the Se-TP administration. In conclusion, Se-TP treatments on CFS rats improved their condition. Its metabolic mechanism was closely related to that which regulates the steroid hormone biosynthesis.

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Metabonomics Study of Ginseng Glycoproteins on Improving Sleep Quality in Mice

BioMed Research International ◽

10.1155/2019/2561828 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Ying Wang ◽

Difu Zhu ◽

Yinghong Chen ◽

Ruizhi Jiang ◽

Hong Xu ◽

...

Keyword(s):

Sleep Quality ◽

Brain Metabolism ◽

Gas Chromatography Mass Spectrometry ◽

Control Group ◽

Glutamate Metabolism ◽

Multivariate Statistical ◽

Hormone Biosynthesis ◽

The Relationship ◽

Further Development

The changes of brain metabolism in mice after injection of ginseng glycoproteins (GPr) were analyzed by gas chromatography mass spectrometry- (GC/MS-) based metabolomics platform. The relationship between sedative and hypnotic effects of ginseng glycoproteins and brain metabolism was discussed. Referring to pentobarbital sodium subthreshold test, we randomly divided 20 mice into two groups: control and ginseng glycoproteins group. The mice from the control group were treated with normal saline by i.p and GPr group were treated with 60 mg/kg of GPr by i.p. The results indicated that GPr could significantly improve the sleep quality of mice. Through multivariate statistical analysis, we found that there were 23 differential metabolites in whole brain tissues between the control group and the GPr group. The pathway analysis exhibited that GPr may be involved in the regulation of the pathway including purine metabolism, nicotinate and nicotinamide metabolism, glycine, serine and threonine metabolism, arginine and proline metabolism, alanine, aspartate and glutamate metabolism, and steroid hormone biosynthesis. This work is helpful to understand the biochemical mechanism of GPr on promoting sleep and lay a foundation for further development of drugs for insomnia.

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