scholarly journals Effects of Platycodins Folium on Depression in Mice Based on a UPLC-Q/TOF-MS Serum Assay and Hippocampus Metabolomics

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1712 ◽  
Author(s):  
Cuizhu Wang ◽  
Hongqiang Lin ◽  
Na Yang ◽  
Han Wang ◽  
Yan Zhao ◽  
...  
Keyword(s):  
Acid Metabolism ◽  
Inositol Phosphate ◽  
Preference Test ◽  
Tail Suspension Test ◽  
Arachidonic Acid Metabolism ◽  
Antidepressant Effect ◽  
Glutathione Metabolism ◽  
Triterpenoid Saponins ◽  
Inositol Phosphate Metabolism ◽  
Tof Ms

Major depressive disorder (MDD), also known as depression, is a state characterized by low mood and aversion to activity. Platycodins Folium (PF) is the dried leaf of Platycodon grandiflorum, with anti-inflammatory and antioxidative activities. Our previous research suggested that PF was rich in flavonoids, phenols, organic acids, triterpenoid saponins, coumarins and terpenoids. This study aimed to investigate the antidepressant effect of PF using lipopolysaccharide (LPS)-induced depressive mice. Several behavior tests (sucrose preference test (SPT), forced swimming test (FST) and tail suspension test (TST)) and biochemical parameters (IL-6, TNF-α and SOD levels) were used to evaluate the antidepressive effect of PF on LPS-induced depression model. Furthermore, a UPLC-Q/TOF-MS-based metabolomics approach was applied to explore the latent mechanism of PF in attenuating depression. As a result, a total of 21 and 11 metabolites that potentially contribute to MDD progress and PF treatment were identified in serum and hippocampus, respectively. The analysis of metabolic pathways revealed that lipid metabolism, amino acid metabolism, energy metabolism, arachidonic acid metabolism, glutathione metabolism and inositol phosphate metabolism were disturbed in a model of mice undergoing MDD and PF treatment. These results help us to understand the pathogenesis of depression in depth, and to discover targets for clinical diagnosis and treatment. They also provide the possibility of developing PF into an anti-depressantive agent.

scholarly journals Molecular Characterization of Advanced Colorectal Cancer Using Serum Proteomics and Metabolomics

2021 ◽  
Author(s):  
Jun Rao ◽  
Xianghui Wan ◽  
Fangfang Tou ◽  
Qinsi He ◽  
Aihua Xiong ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Characterization ◽  
Arachidonic Acid Metabolism ◽  
Health Concern ◽  
Glutathione Metabolism ◽  
Serum Samples ◽  
Serum Proteomics ◽  
Potential Biomarkers ◽  
Tof Ms

Abstract Introduction Colorectal cancer (CRC) is a growing public health concern with high mortality rate. However, there are no valid diagnostic biomarkers and few therapeutic strategies available for CRC, especially advanced CRC, since the pathogenic mechanisms remain poorly understood. Objective To comprehensively reveal molecular characterization of advanced CRC, we applied integrated proteomic and metabolomic analyses on serum samples from 20 patients with CRC at stage III or IV. Methods In the present study, we took advantage of nanoscale liquid chromatography and quadrupole time-of-flight tandem mass spectrometry (nanoLC/Q-TOF-MS/MS) and ultraperformance LC/Q-TOF-MS/MS technologies. Results Overall, 551 proteins and 719 metabolites were identified in those serum samples, respectively. Hierarchical clustering analysis indicated much more remarkable diversity in proteomic profiles than metabolomic profiles. Further functional analysis suggested that ten key pathways associated with cancer cell metabolism were dissected including glycolysis/gluconeogenesis, biosynthesis of amino acids, glutathione metabolism, and arachidonic acid metabolism, based on which protein-protein interaction network analysis was thus constructed with 80 proteins and 21 metabolites. Moreover, the regulatory network in advanced CRC was established according to correlation analysis, indicating conserved roles of metabolome and lipids & lipid like molecules in human serum. Nevertheless, three metabolites and two proteins including hydroquinone, leucenol and sphingomyelin were supposed to be potential biomarkers, which were determined to be positively and significantly correlated with CEA and/or CA 19-9.Conclusions Altogether, our work not only extended our understanding on the physiopathology of advanced CRC, but provided potential biomarkers to improve the accuracy of the diagnosis and monitoring of the syndrome.

scholarly journals Jianpi Jieyu Decoction, An Empirical Herbal Formula, Exerts Psychotropic Effects in Association With Modulation of Gut Microbial Diversity and GABA Activity

2021 ◽  
Vol 12 ◽  
Author(s):  
Lanying Liu ◽  
Zhilu Zou ◽  
Jiangwei Yang ◽  
Xiaoqi Li ◽  
Boran Zhu ◽  
...  
Keyword(s):  
Serum Level ◽  
Gut Microbiota ◽  
Forced Swim Test ◽  
Preference Test ◽  
Tail Suspension Test ◽  
Antidepressant Effect ◽  
Mild Stress ◽  
Gamma Aminobutyric Acid ◽  
Object Recognition Test ◽  
Microbial Distribution

Background: Recent studies suggest that gut microbiota was associated with the bidirectional gut-brain axis which could modulate neuropsychological functions of the central nervous system. Gut microbiota could produce gamma aminobutyric acid (GABA) that could modulate the gut–brain axis response. Jianpi Jieyu (JPJY) decoction, a traditional Chinese formula, is mainly composed of Astragalus membranaxeus and Radix Pseudostellariae. Although the JPJY decoction has been used to treat the depression in China, the potential action of its antidepressant has not been well understood. Thus this study was aim to investigate the role of JPJY improve gut microbiota homeostasis in the chronic stress induced depressive mice.Methods: The antidepressant effect of JPJY on chronic unpredictable mild stress (CUMS) mice was evaluated by using sucrose preference test, tail suspension test and forced swim test. Fatigue-like behaviors were evaluated using degree of redness, grip strength test, and exhaustive swimming test. The new object recognition test was used to evaluate cognition performance. Fecal samples were collected and taxonomical analysis of intestinal microbial distribution was conducted with 16S rDNA. Serum level of GABA was measured using high performance liquid chromatography (HPLC). The expression of GluR1 and p-Tau protein in the hippocampus was determined using Western blotting.Results: The dose of 9.2 g/kg JPJY produced antidepressant-like effects. JPJY and its major components also modulated gut microbiota diversity in the CUMS mice. Serum level of GABA and the expressions of hippocampal GluR1 and p-Tau were reversed after the administration of JPJY in CUMS mice.Conclusion: JPJY regulates gut microbiota to produce antidepressant-like effect and improve cognition deficit in depressive mice while its molecular mechanism possibly be enhanced NR1 and Tau expression in hippocampus and increased GABA in serum.

scholarly journals Tetragonia tetragonioides Relieves Depressive-Like Behavior through the Restoration of Glial Loss in the Prefrontal Cortex

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Yujin Choi ◽  
Yunna Kim ◽  
Hwa-Young Lee ◽  
Seung-Hun Cho
Keyword(s):  
Prefrontal Cortex ◽  
Preference Test ◽  
Tail Suspension Test ◽  
Antidepressant Effect ◽  
Antidepressant Agent ◽  
Immobility Time ◽  
Swimming Test ◽  
Asian Pacific ◽  
Sucrose Preference Test ◽  
Tetragonia Tetragonioides

Tetragonia tetragonioides, which is a halophyte and grows widely in Asian-Pacific regions, has been used for the treatment of digestive disorders in traditional oriental medicine. This study examined the potential antidepressant effect of Tetragonia tetragonioides in an astroglial degeneration model of depression, which was established based on the postmortem study of depressive patients’ brain presenting diminished astrocytes in the prefrontal cortex. C57BL/6 male mice were exposed to glial ablation in the prefrontal cortex by the administration of the gliotoxin, L-alpha-aminoadipic acid (L-AAA) to induce depression. Tetragonia tetragonioides at doses of 100 mg/kg and 300 mg/kg, imipramine at a dose of 15 mg/kg, and distilled water were orally administrated to mice for 18 days. Behavioral tests including the open field test (OFT), sucrose preference test (SPT), forced swimming test (FST), and tail suspension test (TST) were carried out after 2 days of L-AAA injection. The expression levels of GFAP and NeuN in the prefrontal cortex were determined by immunohistochemistry. Mice subjected to glial ablation in the prefrontal cortex displayed decreased sucrose consumption in SPT and increased immobility time in FST and TST. Treatment with imipramine and Tetragonia tetragonioides remarkably ameliorated the behavioral despair induced by L-AAA. In addition, immunohistochemistry analysis showed that treatment with Tetragonia tetragonioides significantly restored the glial loss as indicated by the elevated GFAP expression level. These findings suggest that Tetragonia tetragonioides exerts an antidepressant effect through the restoration of glial loss under conditions of depression and can be a candidate for an antidepressant agent.

scholarly journals QGQS Granule in SHR Serum Metabonomics Study Based on Tools of UPLC-Q-TOF and Renin-Angiotensin-Aldosterone System Form Protein Profilin-1

2017 ◽  
Vol 2017 ◽  
pp. 1-13
Author(s):  
Ke Li ◽  
Caicai Li ◽  
Jialong Wang ◽  
Hanming Cui ◽  
Yu Dong ◽  
...  
Keyword(s):  
Acid Metabolism ◽  
Arachidonic Acid Metabolism ◽  
Control Group ◽  
Ang Ii ◽  
Sample Analysis ◽  
Model Group ◽  
Tail Artery ◽  
Endogenous Metabolites ◽  
Tof Ms

QGQS granule is effective for the therapeutic of hypertension in clinic. The aim of this research is to observe the antihypertension effect of QGQS granule on SHR and explain the mechanism of its lowering blood pressure. 30 SHR were selected as model group, captopril group, and QGQS group, 10 WKYr were used as control group, and RBP were measured on tail artery consciously. And all the serum sample analysis was carried out on UPLC-TOF-MS system to determine endogenous metabolites and to find the metabonomics pathways. Meanwhile, ELISA kits for the determination pharmacological indexes of PRA, AngI, AngII, and ALD were used for pathway confirmatory; WB for determination of profilin-1 protein expression was conducted for Ang II pathway analysis as well. It is demonstrated that QGQS granule has an excellent therapeutic effect on antihypertension, which exerts effect mainly on metabonomics pathway by regulating glycerophospholipid, sphingolipid, and arachidonic acid metabolism, and it could inhibit the overexpression of the profilin-1 protein. We can come to a conclusion that RAAS should be responsible mainly for the metabonomics pathway of QGQS granule on antihypertension, and it plays a very important role in protein of profilin-1 inhibition.

scholarly journals Beneficial Effects of Crocin against Depression via Pituitary Adenylate Cyclase-Activating Polypeptide

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Linyu Lu ◽  
Die Wu ◽  
Kai Wang ◽  
Juanjuan Tang ◽  
Gang Chen
Keyword(s):  
Adenylate Cyclase ◽  
Pc12 Cells ◽  
Neuroprotective Effect ◽  
Preference Test ◽  
Tail Suspension Test ◽  
Adenosine Monophosphate ◽  
Underlying Mechanism ◽  
Antidepressant Effect ◽  
Mild Stress ◽  
Pituitary Adenylate Cyclase

Depression is one of the foremost psychological illness, and the exact mechanism is unclear. Recent studies have reported that the pituitary adenylate cyclase-activating polypeptide (PACAP) signaling pathway is involved in the progression of depression. In the present study, we extracted crocin from the traditional Chinese medicine (TCM), Gardenia jasminoides Ellis, to evaluate its antidepressant effect and clarify the underlying mechanism. Here, we established a chronic unpredictable mild stress (CUMS) mouse model to assess whether crocin can improve depression-like behavior in an open field test (OFT), tail suspension test (TST), forced swimming test (FST), and sucrose preference test (SPT). A corticosterone (CORT) model of PC12 was set up to explore the antidepressant mechanism of crocin. We pretreated PC12 cells with crocin for 1 hour and then stimulated the cells with CORT for 24 hours. Cell survival was detected by Hoechst staining and MTT assay. The expression of PACAP, cyclic adenosine monophosphate (cAMP) response element binding protein (CREB), and extracellular regulated protein kinases (ERK) were analyzed by western blotting. PACAP RNAi was used to interfere with PC12 cells to downregulate the content of PACAP. The results showed that crocin (30 mg/kg) significantly reversed the decrease of body weight and elevation of serum CORT, mitigated CUMS induced depression-like behaviors of mice, and crocin (12.5 μmol/L) protected PC12 cells against CORT (200 μmol/L)-induced injury. Furthermore, crocin greatly increased the protein expression of PACAP and phosphorylation of ERK and CREB in the CORT model. PACAP RNAi cancelled the neuroprotective effect of crocin. In conclusion, these results indicated that crocin exerted an antidepressant effect via upregulating PACAP and its downstream ERK and CREB signaling pathways.

scholarly journals The autistic-like behaviors development during weaning and sexual maturation in VPA-induced autistic-like rats is accompanied by gut microbiota dysbiosis

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11103
Author(s):  
Qingmin Kong ◽  
Peijun Tian ◽  
Jianxin Zhao ◽  
Hao Zhang ◽  
Gang Wang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Propionic Acid ◽  
Butyric Acid ◽  
Sexual Maturation ◽  
Developmental Disorders ◽  
Acid Metabolism ◽  
Inositol Phosphate ◽  
Age Groups ◽  
Short Chain Fatty Acids ◽  
Inositol Phosphate Metabolism

Researches on gut microbiota in autism have mostly focused on children, but the dynamic changes of gut microbiota from weaning to adulthood were still not clear because of the difficulty of diagnosing autism. In this study, autistic-like rats indued by valproate (VPA) were tracked from weaning (end of breastfeeding; four weeks old) to sexual maturation (food; eight weeks old). Autistic-like rats were found to show obvious developmental disorders. During weaning, autistic-like rats only exhibited obvious repetitive stereotyped behaviors, but the autistic-like behaviors were fully apparent upon sexual maturation. Significant differences were observed between the gut microbiota of autistic-like and healthy rats across both age groups. The correlation analysis results revealed that the correlation between behaviors and some microbiota, especially Helicobacter, did not vary with age or diet. The total amount of short-chain fatty acids (SCFAs) decreased, butyric acid metabolism decreased, and propionic acid metabolism increased in the feces of autistic-like rats. The correlation between autistic-like behaviors and the butyric acid and propionic acid levels did not vary with diet or age. Inositol phosphate metabolism, amino acid metabolism, and lipopolysaccharide biosynthesis were significantly associated with autistic-like behaviors. Our results showed that although the microbiota and SCFAs related to autism were affected by age and diet, some remained consistent irrespective of age and diet, and they could be considered two of the factors related to autistic-like behaviors development.

scholarly journals High-Throughput Untargeted Serum Metabolomics Analysis of Hyperuricemia Patients by UPLC-Q-TOF/MS

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Nankun Qin ◽  
Yue Jiang ◽  
Wenjun Shi ◽  
Liting Wang ◽  
Lingbo Kong ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Linoleic Acid ◽  
Metabolic Pathways ◽  
Acid Metabolism ◽  
Arachidonic Acid Metabolism ◽  
Sphingolipid Metabolism ◽  
Tryptophan Biosynthesis ◽  
Linoleic Acid Metabolism ◽  
Phenylalanine Metabolism ◽  
Tof Ms

Hyperuricemia (HUA) as a metabolic disease is closely associated with metabolic disorders. The etiology and pathogenesis of HUA are not fully understood, so there is no radical cure so far. Metabolomics, a specialized study of endogenous small molecule substances, has become a powerful tool for metabolic pathway analysis of selected differential metabolites, which is helpful for initially revealing possible development mechanisms of various human diseases. Twenty HUA patients and 20 healthy individuals participated in the experiment, and ultrahigh performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS) was employed to investigate serum samples to find differential metabolites. The statistical techniques used were principal component analysis and orthogonal partial least-squares discriminant analysis. The differences in metabolomics results of samples after pretreatment with different solvents were compared, 38, 20, 26, 28, 33, 50, and 40 potential differential metabolites were found, respectively, in HUA patient samples, and each group involved different metabolic pathways. Repetitive metabolites were removed, 138 differential metabolites in HUA serum were integrated for analysis, and the human body was affected by 7 metabolic pathways of glycerophospholipid metabolism, sphingolipid metabolism, arachidonic acid metabolism, linoleic acid metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and α-linolenic acid metabolism. In this work, the metabolomics approach based on UPLC-Q-TOF/MS was employed to investigate serum metabolic changes in HUA patients, 138 potential differential metabolites related to HUA were identified, which provided associations of lipids, amino acids, fatty acids, organic acids, and nucleosides profiles of HUA individuals. Metabolic pathways involved in glycerophospholipid metabolism, sphingolipid metabolism, arachidonic acid metabolism, linoleic acid metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and a-linolenic acid metabolism shed light on the understanding of the etiology and pathogenesis process of HUA.

scholarly journals Dietary phosphorus and calcium in feed affects miRNA profiles and their mRNA targets in jejunum of two strains of laying hens

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Muhammad Arsalan Iqbal ◽  
Asghar Ali ◽  
Frieder Hadlich ◽  
Michael Oster ◽  
Henry Reyer ◽  
...  
Keyword(s):  
Egg Production ◽  
Target Genes ◽  
Laying Hens ◽  
Inositol Phosphate ◽  
Glutathione Metabolism ◽  
Mrna Targets ◽  
Inositol Phosphate Metabolism ◽  
Dietary Phosphorus ◽  
Different Levels ◽  
P Bioavailability

AbstractPhosphorus (P) and calcium (Ca) are critical for egg production in laying hens. Most of P in plant-based poultry diet is bound as phytic acid and needs to be hydrolysed before absorption. To increase P bioavailability, exogenous phytases or bioavailable rock phosphate is added in feed. There is growing evidence of the importance of miRNAs as the epicentre of intestinal homeostasis and functional properties. Therefore, we demonstrated the expression of miRNA profiles and the corresponding target genes due to the different levels of P (recommended vs. 20% reduction) and/or Ca (recommended vs. 15% reduction) in feed. Jejunal miRNA profiles of Lohmann Selected Leghorn (LSL) and Lohmann Brown (LB) laying hens strains were used (n = 80). A total of 34 and 76 miRNAs were differentially expressed (DE) in the different diet groups within LSL and LB strains respectively. In LSL, the DE miRNAs and their targets were involved in calcium signaling pathway, inositol phosphate metabolism, and mitochondrial dysfunction. Similarly, in LB miRNAs targets were enriched in metabolic pathways such as glutathione metabolism, phosphonate metabolism and vitamin B6 metabolism. Our results suggest that both strains employ different intrinsic strategies to cope with modulated P and Ca supply and maintain mineral homeostasis.

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