scholarly journals Study the Mechanism of Antileishmanial Action of Xanthium strumarium Against Amastigotes Stages in Leishmania major: A Metabolomics Approach

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Mohamad Ahmadi ◽  
Ziba Akhbari ◽  
Zahra Zamani ◽  
Reza Hajhossieni ◽  
Mohammad Arjmand
Keyword(s):  
Metabolic Pathways ◽  
Leaf Extract ◽  
Leishmania Major ◽  
Colorimetric Method ◽  
Sugar Metabolism ◽  
Amino Sugar ◽  
Primary Treatment ◽  
Antileishmanial Activity ◽  
Xanthium Strumarium ◽  
Galactose Metabolism

Background: Leishmaniasis is among the most important neglected tropical infections, affecting millions of people worldwide. Since 1945, chemotherapy has been the primary treatment for leishmaniasis; however, lengthy and costly treatments associated with various side effects and strains resistant to the conventional therapy have dramatically reduced chemotherapy compounds’ efficacy. Objectives: The antileishmanial activity of the leaf extract of Xanthium strumarium (Asteraceae) was studied. New insights into its mechanism of action toward Leishmania major were provided through a metabolomics-based study. Methods: J774 macrophages were cultured, infected with stationary promastigotes, and treated with different leaf extract concentrations for three days. Antileishmanial activity was assayed by the MTT colorimetric method, and cell metabolites were extracted. 1HNMR spectroscopy was applied, and outliers were analyzed using multivariate statistical analysis. Results: X. strumarium extract (0.15 µg/mL) showed the best activity against L. major amastigotes with the infection rate (IR) and multiplication index (MI) values of 51% and 57%, respectively. The action of X. strumarium extract on amastigotes was comparable with amphotericin B as the positive control (0.015 µg/mL). According to the obtained P-values, pentanoate and coenzyme, A biosynthesis, pentose, glucuronate metabolism, valine, leucine, isoleucine biosynthesis, galactose metabolism, and amino sugar and nucleotide sugar metabolism were the most important metabolic pathways affected by the plant extract in the amastigote stage of L. major. Conclusions: Our finding demonstrated that X. strumarium leaf extract could be used for discovering and producing novel leishmanicidal medicines. Moreover, the affected metabolic pathways observed in this study could be potential candidates for drug targeting against leishmaniasis.

scholarly journals Metabolomics Based Study of the Antileishmanial Activity of Xanthium strumarium Leaf Extract on Promastigotes Phases of Leishmania major by Proton NMR Spectroscopy

2019 ◽  
Author(s):  
Mohammad AHMADI ◽  
Ziba AKBARI ◽  
Mahbobeh ALIKHANI ◽  
Reza HAJHOSSIANI ◽  
Zahra ZAMANI ◽  
...  
Keyword(s):  
Nmr Spectroscopy ◽  
Metabolic Pathways ◽  
Leaf Extract ◽  
Leishmania Major ◽  
Stationary Phases ◽  
Treatment Strategies ◽  
Growth Inhibitor ◽  
Antileishmanial Activity ◽  
Xanthium Strumarium ◽  
Galactose Metabolism

Background: Xanthium strumarium L. is extensively used as a traditional herb to treat many diseases and is also known as a source of phytochemicals. It has been used traditionally to treat trypanosomiasis, malaria fever, eczema, cancer, ulcer, fever, herpes headache, and skin lesion such as leishmaniasis. In this preliminary study, nuclear magnetic resonance (NMR)-metabolomics approaches was used to evaluate the inhibitory effects and metabolic alterations caused by leaf extract of X. strumarium on the stationary phases of promastigotes in Leishmania major. Methods: The promastigotes were cultured in Biochemistry Laboratory at Pasteur Institute of Iran in 2017, stationary phases were obtained from 5 to 6 day-old cultures and treated with different concentrations of the plant’s extract. Antileishmanial activity was assayed by MTT method and cell metabolites were extracted. 1H NMR spectroscopy was applied, and outliers were separated using multivariate statistical analysis. Results: The most affected metabolic pathways in the experimental groups were limited to amino sugar and nucleotide sugar metabolism, cyanoamino acid metabolism, starch and sucrose metabolism, butanoate metabolism, and galactose metabolism. Conclusion: The ethanolic leaf extract of X. strumarium is a potent growth inhibitor of Leishmania major and can affect vital metabolic pathways of Leishmania promastigotes. The assay provided new perspectives on the development of novel treatment strategies for leishmanial activity derived from natural products.

scholarly journals Transcriptomics and metabolomics reveal the adaption of Akkermansia muciniphila to high mucin by regulating energy homeostasis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xinyue Liu ◽  
Fan Zhao ◽  
Hui Liu ◽  
Yunting Xie ◽  
Di Zhao ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
Sugar Metabolism ◽  
Amino Sugar ◽  
Gas Chromatography Mass Spectrometry ◽  
Galactose Metabolism ◽  
Nucleotide Sugar ◽  
Akkermansia Muciniphila ◽  
Acetylneuraminic Acid ◽  
Metabolic Characteristics ◽  
Culture Environment

AbstractIn gut, Akkermansia muciniphila (A. muciniphila) probably exerts its probiotic activities by the positive modulation of mucus thickness and gut barrier integrity. However, the potential mechanisms between A. muciniphila and mucin balance have not been fully elucidated. In this study, we cultured the bacterium in a BHI medium containing 0% to 0.5% mucin, and transcriptome and gas chromatography mass spectrometry (GC–MS) analyses were performed. We found that 0.5% (m/v) mucin in a BHI medium induced 1191 microbial genes to be differentially expressed, and 49 metabolites to be changed. The metabolites of sorbose, mannose, 2,7-anhydro-β-sedoheptulose, fructose, phenylalanine, threonine, lysine, ornithine, asparagine, alanine and glutamic acid were decreased by 0.5% mucin, while the metabolites of leucine, valine and N-acetylneuraminic acid were increased. The association analysis between transcriptome and metabolome revealed that A. muciniphila gave strong responses to energy metabolism, amino sugar and nucleotide sugar metabolism, and galactose metabolism pathways to adapt to high mucin in the medium. This finding showed that only when mucin reached a certain concentration in a BHI medium, A. muciniphila could respond to the culture environment significantly at the level of genes and metabolites, and changed its metabolic characteristics by altering the effect on carbohydrates and amino acids.

scholarly journals Integrative Metabolic Pathway Analysis Reveals Novel Therapeutic Targets in Osteoarthritis

2020 ◽  
Vol 19 (4) ◽  
pp. 574-588 ◽  
Author(s):  
Beatriz Rocha ◽  
Berta Cillero-Pastor ◽  
Gert Eijkel ◽  
Valentina Calamia ◽  
Patricia Fernandez-Puente ◽  
...  
Keyword(s):  
Pathway Analysis ◽  
Metabolic Pathways ◽  
Therapeutic Targets ◽  
Sugar Metabolism ◽  
Cartilage Regeneration ◽  
Amino Sugar ◽  
Acid Synthesis ◽  
Ionization Mass ◽  
Metabolic Pathway Analysis ◽  
Molecular Alterations

In osteoarthritis (OA), impairment of cartilage regeneration can be related to a defective chondrogenic differentiation of mesenchymal stromal cells (MSCs). Therefore, understanding the proteomic- and metabolomic-associated molecular events during the chondrogenesis of MSCs could provide alternative targets for therapeutic intervention. Here, a SILAC-based proteomic analysis identified 43 proteins related with metabolic pathways whose abundance was significantly altered during the chondrogenesis of OA human bone marrow MSCs (hBMSCs). Then, the level and distribution of metabolites was analyzed in these cells and healthy controls by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), leading to the recognition of characteristic metabolomic profiles at the early stages of differentiation. Finally, integrative pathway analysis showed that UDP-glucuronic acid synthesis and amino sugar metabolism were downregulated in OA hBMSCs during chondrogenesis compared with healthy cells. Alterations in these metabolic pathways may disturb the production of hyaluronic acid (HA) and other relevant cartilage extracellular matrix (ECM) components. This work provides a novel integrative insight into the molecular alterations of osteoarthritic MSCs and potential therapeutic targets for OA drug development through the enhancement of chondrogenesis.

scholarly journals Effect of a Humanized Diet Profile on Colonization Efficiency and Gut Microbial Diversity in Human Flora-Associated Mice

2021 ◽  
Vol 8 ◽  
Author(s):  
Sashuang Dong ◽  
BenHua Zeng ◽  
Ling Hu ◽  
Yuling Zhang ◽  
Jiaqi Xiong ◽  
...  
Keyword(s):  
Microbial Diversity ◽  
Mouse Models ◽  
Metabolic Pathways ◽  
Intestinal Flora ◽  
Sugar Metabolism ◽  
Amino Sugar ◽  
Nucleotide Sugar ◽  
Human Donor ◽  
Disease Research ◽  
Human Flora

Human flora-associated (HFA) mouse models allow us to design interventions for human disease research to test specific hypotheses and explore the complex commensal microbiome while avoiding the ethical limitations of using humans as models to directly study intestinal flora diseases. However, few studies have investigated the effect of a humanized diet profile (coarse-feed diet; CFD) on colonization efficiency and gut microbial diversity in HFA mice. We tested the colonization efficiency and gut microbial diversity in germ-free Kunming (KM) mice fed a CFD or a purified feed diet (PFD) at 1, 2, and 4 weeks. Although the colonization efficiencies differed significantly (67.50–70.00% vs. 72.69–85.96%) in the HFA mice, the colonization efficiency of the PFD-fed HFA mice (85.96%) was significantly higher than that of the CFD-fed mice (69.61%) at 2 weeks. At 4 weeks, the colonization efficiency of the PFD-fed mice (72.69%) was comparable to that of the CFD-fed mice (70.00%). Additionally, the gut microbial diversity of the CFD-fed HFA mice was similar to that of a human fecal donor. Regarding the Kyoto Encyclopedia of Genes and Genomes colonic microbiota metabolic pathways, the CFD-fed HFA mice showed more similarities to the human donor than to the PFD-fed mice in amino sugar and nucleotide sugar metabolism, biosynthesis of amino acids, carbon metabolism, purine metabolism, and phosphotransferase systems. In conclusion, the humanized diet profiles of the CFD and PFD could help establish human microbiotas in mice. Constructing HFA mouse models fed a CFD for 4 weeks may be useful in researching human-derived intestinal diseases.

scholarly journals Comparative Proteomic Analysis of Grapevine Rootstock in Response to Waterlogging Stress

2021 ◽  
Vol 12 ◽  
Author(s):  
Xicheng Wang ◽  
Lichun Yan ◽  
Bo Wang ◽  
Yaming Qian ◽  
Zhuangwei Wang ◽  
...  
Keyword(s):  
Carbon Fixation ◽  
Sugar Metabolism ◽  
Enrichment Analysis ◽  
Amino Sugar ◽  
Resistance Mechanisms ◽  
Glutathione Metabolism ◽  
Waterlogging Tolerance ◽  
Galactose Metabolism ◽  
Waterlogging Stress ◽  
Waterlogging Treatment

Waterlogging severely affects global agricultural production. Clarifying the regulatory mechanism of grapevine in response to waterlogging stress will help to improve the waterlogging tolerance of grapevine. In the present study, the physiological and proteomic responses of SO4 grapevine rootstock to different waterlogging tolerances were comparatively assayed. The results showed that the activities of SOD and POD first increased and then decreased, while the change trend of CAT and APX activities was the opposite. In addition, the MDA and H2O2 contents increased after waterlogging treatment, but the chlorophyll a and chlorophyll b contents decreased. A total of 5,578 grapevine proteins were identified by the use of the tandem mass tag (TMT) labeling technique. Among them, 214 (103 and 111 whose expression was upregulated and downregulated, respectively), 314 (129 and 185 whose expression was upregulated and downregulated, respectively), and 529 (248 and 281 whose expression was upregulated and downregulated, respectively) differentially expressed proteins (DEPs) were identified in T0d vs. T10d, T10d vs. T20d, and T0d vs. T20d comparison groups, respectively. Enrichment analysis showed that these DEPs were mainly involved in glutathione metabolism, carbon fixation, amino sugar and nucleotide sugar metabolism, biosynthesis of amino acids, photosynthesis, carbon metabolism, starch, and sucrose metabolism, galactose metabolism, protein processing and ribosomes. To further verify the proteomic data, the expression of corresponding genes that encode eight DEPs was confirmed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). The results of this study presented an important step toward understanding the resistance mechanisms of grapevine in response to waterlogging stress at the proteome level.

scholarly journals In Vitro Antileishmanial Activity of Nicotinamide

2005 ◽  
Vol 49 (2) ◽  
pp. 808-812 ◽  
Author(s):  
D. Sereno ◽  
A. Monte Alegre ◽  
R. Silvestre ◽  
B. Vergnes ◽  
A. Ouaissi
Keyword(s):  
Leishmania Major ◽  
Growth Arrest ◽  
Antileishmanial Activity ◽  
Vitamin B ◽  
Wild Type ◽  
Intracellular Growth ◽  
Cell Growth Arrest ◽  
Transgenic Parasites

ABSTRACT Our study represents the first report demonstrating the antileishmanial activity of nicotinamide (NAm), a form of vitamin B3. A 5 mM concentration of NAm significantly inhibited the intracellular growth of Leishmania amastigotes and the NAD-dependent deacetylase activity carried by parasites overexpressing Leishmania major SIR2 (LmSIR2). However, the transgenic parasites were as susceptible as the wild-type parasites to NAm-induced cell growth arrest. Therefore, we conclude that NAm inhibits leishmanial growth and that overexpression of LmSIR2 does not overcome this inhibition. The mechanism of the inhibition is not defined but may include other in vivo targets. NAm may thus represent a new antileishmanial agent which could potentially be used in combination with other drugs during therapy.

scholarly journals Alterations of gut microbiota in gestational diabetes patients during the second trimester of pregnancy in the Shanghai Han population

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yao Su ◽  
Hong-Kun Wang ◽  
Xu-Pei Gan ◽  
Li Chen ◽  
Yan-Nan Cao ◽  
...  
Keyword(s):  
Gestational Diabetes ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Sugar Metabolism ◽  
16S Rrna Gene Sequencing ◽  
Amino Sugar ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Second Trimester ◽  
Metabolic Hormone

Abstract Background The causes of gestational diabetes mellitus (GDM) are still unclear. Recent studies have found that the imbalance of the gut microbiome could lead to disorders of human metabolism and immune system, resulting in GDM. This study aims to reveal the different gut compositions between GDM and normoglycemic pregnant women and find the relationship between gut microbiota and GDM. Methods Fecal microbiota profiles from women with GDM (n = 21) and normoglycemic women (n = 32) were assessed by 16S rRNA gene sequencing. Fasting metabolic hormone concentrations were measured using multiplex ELISA. Results Metabolic hormone levels, microbiome profiles, and inferred functional characteristics differed between women with GDM and healthy women. Additionally, four phyla and seven genera levels have different correlations with plasma glucose and insulin levels. Corynebacteriales (order), Nocardiaceae (family), Desulfovibrionaceae (family), Rhodococcus (genus), and Bacteroidetes (phylum) may be the taxonomic biomarkers of GDM. Microbial gene functions related to amino sugar and nucleotide sugar metabolism were found to be enriched in patients with GDM. Conclusion Our study indicated that dysbiosis of the gut microbiome exists in patients with GDM in the second trimester of pregnancy, and gut microbiota might be a potential diagnostic biomarker for the diagnosis, prevention, and treatment of GDM.

scholarly journals The keystone species of Precambrian deep bedrock biosphere belong to <i>Burkholderiales</i> and <i>Clostridiales</i>

2015 ◽  
Vol 12 (21) ◽  
pp. 18103-18150 ◽  
Author(s):  
L. Purkamo ◽  
M. Bomberg ◽  
R. Kietäväinen ◽  
H. Salavirta ◽  
M. Nyyssönen ◽  
...  
Keyword(s):  
Microbial Communities ◽  
Carbon Fixation ◽  
Keystone Species ◽  
Carbon Assimilation ◽  
Sugar Metabolism ◽  
Archaeal Community ◽  
Amino Sugar ◽  
Amplicon Sequencing ◽  
Fracture Zones ◽  
Crystalline Bedrock

Abstract. The bacterial and archaeal community composition and the possible carbon assimilation processes and energy sources of microbial communities in oligotrophic, deep, crystalline bedrock fractures is yet to be resolved. In this study, intrinsic microbial communities from six fracture zones from 180–2300 m depths in Outokumpu bedrock were characterized using high-throughput amplicon sequencing and metagenomic prediction. Comamonadaceae-, Anaerobrancaceae- and Pseudomonadaceae-related OTUs form the core community in deep crystalline bedrock fractures in Outokumpu. Archaeal communities were mainly composed of Methanobacteraceae-affiliating OTUs. The predicted bacterial metagenomes showed that pathways involved in fatty acid and amino sugar metabolism were common. In addition, relative abundance of genes coding the enzymes of autotrophic carbon fixation pathways in predicted metagenomes was low. This indicates that heterotrophic carbon assimilation is more important for microbial communities of the fracture zones. Network analysis based on co-occurrence of OTUs revealed the keystone genera of the microbial communities belonging to Burkholderiales and Clostridiales. Bacterial communities in fractures resemble those found from oligotrophic, hydrogen-enriched environments. Serpentinization reactions of ophiolitic rocks in Outokumpu assemblage may provide a source of energy and organic carbon compounds for the microbial communities in the fractures. Sulfate reducers and methanogens form a minority of the total microbial communities, but OTUs forming these minor groups are similar to those found from other deep Precambrian terrestrial bedrock environments.

scholarly journals STRUCTURE AND FUNCTION OF THE FRUIT MICROBIOME IN HEALTHY AND DISEASED KIWIFRUIT

2019 ◽  
Vol 56 (03) ◽  
pp. 577-585
Author(s):  
Wenneng Wu
Keyword(s):  
Microbial Diversity ◽  
Relative Abundance ◽  
Foodborne Pathogens ◽  
Fungal Pathogens ◽  
Sugar Metabolism ◽  
Amino Sugar ◽  
Disease Diagnosis ◽  
Postharvest Disease ◽  
Pathogen Infection ◽  
Microbiome Composition

The fruit surface is an infection court where foodborne pathogens compete with indigenous microbiota for microsites to invade the fruits for nutrients acquisition. However, our current understanding of the structure and functions of fruit microbiome visa-vis postharvest pathogen infection is still nascent. Here, we sequenced the metagenomic DNA to understand the structural and functional attributes of healthy and diseased kiwifruit microbiome. The healthy fruits exhibited higher microbial diversity and distinct microbiome composition compared with diseased fruits. The microbiome of diseased fruit was dominated by fungal pathogens Neofusicoccum parvum and Diplodiaseriata, while the microbiome of healthy fruits were enriched by bacteria from Methylobacteriaceae, Sphingomonadaceae, Nocardioidaceae and fungi in Pleosporaceae. Importantly, the healthy fruit microbiome had a higher relative abundance of genes related to ABC transporter, two-component system, bacterial chemotaxis, bacterial secretion system, but had a lower relative abundance of genes associated with polycyclic aromatic hydrocarbon degradation, amino sugar and nucleotide sugar metabolism, glycine, serine and threonine metabolism compared with diseased fruits. Our results indicate that pathogen infection disrupts the fruit microbiome. The changes in microbiome composition and functions could also increase the possibility of secondary pathogen infection as the reduced microbial diversity may demonstrate less resistance to pathogens infection. Therefore, monitoring the microbiome dynamics and their functions using metagenomic approaches could be useful to build a predictive understanding of accurate postharvest disease diagnosis and management in the future

scholarly journals SYZYGIUM CUMINI (L.) SKEELS LEAF EXTRACT FRACTIONS AS ARGINASE INHIBITORS AND THE EFFECTS OF TANNINS ON THEIR ACTIVITY

2020 ◽  
pp. 268-270
Author(s):  
ARI ARIEFAH HIDAYATI ◽  
BERNA ELYA ◽  
RANI SAURIASARI
Keyword(s):  
Ethyl Acetate ◽  
Inhibitory Activity ◽  
Leaf Extract ◽  
Colorimetric Method ◽  
Ethyl Acetate Fraction ◽  
Precipitation Method ◽  
Total Phenolic ◽  
Syzygium Cumini ◽  
Methanol Fraction ◽  
Phenolic And Flavonoid

Objective: Arginase inhibition could be a potential therapeutic approach for endothelial dysfunction. Syzygium cumini (L.) Skeels leaves containphenolic acids and flavonoids, which have been predicted to exhibit arginase inhibitory activity. Moreover, these leaves contain tannins, which canform complexes with enzymes and lead to false-positive results during biological testing. Therefore, this study was conducted to evaluate the arginaseinhibitory activity of S. cumini leaf extract and fractions as well as to elucidate the effects of tannins on this activity.Methods: S. cumini leaves were fractionated using n-hexane, ethyl acetate, and methanol. A colorimetric method was employed to evaluate arginaseinhibitory activity. Tannin elimination was performed through the gelatin precipitation method. Total phenolic and flavonoid contents of the fractionswere calculated using the Folin–Ciocalteu and aluminum chloride methods, respectively.Results: Ethyl acetate and methanol fractions showed arginase inhibitory activity with half-maximal inhibitory concentrations (IC50) of 46.96 and15.35 μg/mL, respectively. The methanol fraction was positive for tannins. After tannin elimination, this fraction exhibited less potent arginaseinhibitory activity, with an IC50 value of 53.03 μg/mL. The ethyl acetate fraction showed higher total phenolic and flavonoid contents than the methanolfraction.Conclusion: Tannins affected the arginase inhibitory activity of the methanol fraction of S. cumini leaves; however, the ethyl acetate fraction did notcontain tannins and could inhibit arginase activity.

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