NMR metabolomic approaches for plants, toxicology and medicine

NMR metabolomic approaches for plants, toxicology and medicine This article describes the principles as well as the analytical and chemometric tools that support the development of NMR metabolomic approaches. These analytical methods are illustrated through a range of selected examples in various domains of biology and medicine, concerning the study of genetically modified organisms, plant/environment interactions, environmental toxicology, pharmacology, cancerology, or molecular epidemiology

Tristaenone A : a new anti-inflammatory compound isolated from the Australian Indigenous plant Tristaniopsis laurina

Inspired by ethnopharmacological knowledge, we conducted a bioassay-guided fractionation of the leaves of Tristaniopsis laurina which led to the discovery of a new anti-inflammatory compound, tristaenone A (1). The structure was elucidated by detailed spectroscopic data analysis, and the absolute configuration was established using X-ray crystallography analysis. Tristaenone A (1) suppressed LPS and IFN-γ-induced NO, TNF-α and IL-6 production in RAW 264.7 cells with IC50 values of 37.58 ± 2.45 μM, 80.6 ± 5.82 μM and 125.65 ± 0.34 μM, respectively. It also inhibited NF-κB nuclear translocation by 52.93 ± 14.14% at a concentration of 31.85 μM

Myrtinols A-F : new anti-inflammatory peltogynoid flavonoid derivatives from the leaves of Australian Indigenous plant Backhousia myrtifolia

Our in-house ethnopharmacological knowledge directed our anti-inflammatory investigation into the leaves of Backhousia mytifolia. Bioassay guided isolation of the Australian indigenous plant Backhousia myrtifolia led to the isolation of six new rare peltogynoid derivatives named myrtinols A–F (1–6) along with three known compounds 4-O-methylcedrusin (7), 7-O-methylcedrusin (8) and 8-demethylsideroxylin (9). The chemical structures of all the compounds were elucidated by detailed spectroscopic data analysis, and absolute configuration was established using X-ray crystallography analysis. All compounds were evaluated for their anti-inflammatory activity by assessing the inhibition of nitric oxide (NO) production and tumor necrosis factor- α (TNF-α) in lipopolysaccharide (LPS) and interferon (IFN)-γ activated RAW 264.7 macrophages. A structure activity relationship was also established between compounds (1–6), noting promising anti-inflammatory potential by compounds 5 and 9 with an IC50 value of 8.51 ± 0.47 and 8.30 ± 0.96 µg/mL for NO inhibition and 17.21 ± 0.22 and 46.79 ± 5.87 µg/mL for TNF-α inhibition, respectively

From the bush to the brain : preclinical stages of ethnobotanical anti-inflammatory and neuroprotective drug discovery : an Australian example

The Australian rainforest is a rich source of medicinal plants that have evolved in the face of dramatic environmental challenges over a million years due to its prolonged geographical isolation from other continents. The rainforest consists of an inherent richness of plant secondary metabolites that are the most intense in the rainforest. The search for more potent and more bioavailable compounds from other plant sources is ongoing, and our short review will outline the pathways from the discovery of bioactive plants to the structural identification of active compounds, testing for potency, and then neuroprotection in a triculture system, and finally, the validation in an appropriate neuro-inflammatory mouse model, using some examples from our current research. We will focus on neuroinflammation as a potential treatment target for neurodegenerative diseases including multiple sclerosis (MS), Parkinson’s (PD), and Alzheimer’s disease (AD) for these plant-derived, anti-inflammatory molecules and highlight cytokine suppressive anti-inflammatory drugs (CSAIDs) as a better alternative to conventional nonsteroidal anti-inflammatory drugs (NSAIDs) to treat neuroinflammatory disorders

Combining Genomics and Metabolomics for the Discovery of Regulatory Genes and Their Use in Metabolic Engineering to Produce ‘Healthy Foods’

Plants often accumulate their natural products to relatively low levels, so there is a lot of interest in breeding or engineering plants that produce higher levels. It has been shown that the most effective way to increase the accumulation of secondary metabolites is to increase the activity of genes that regulate the activity of the biosynthetic pathways that make different natural products. Regulatory genes of this type encode proteins called transcription factors. The biggest bottleneck in using this strategy to develop plants that accumulate significantly higher levels of important natural products is that not many transcription factors regulating secondary metabolism have yet been identified at the molecular level. Genes encoding transcription factors can be identified from model plants with sequenced genomes. The ability of such genes to regulate metabolism can be assayed by examination of mutants (reverse genetics) and by investigating the metabolic effects of high levels of expression of the genes. The combined techniques of metabolic fingerprinting and metabolite profiling of mutant and transgenic plants are allowing us to identify new genes encoding transcription factors controlling secondary metabolism, that can be used as tools for engineering natural product accumulatio

Skeletal muscle metabolomics and blood biochemistry analysis reveal metabolic changes associated with dietary amino acid supplementation in dairy calves

The effects of different amino acid (AA) supplementations of milk protein-based milk replacers in pre-ruminant calves from 3 days to 7 weeks of age were studied. Animals were divided into 4 groups: Ctrl) Control group fed with milk protein-based milk replacer without supplementation; GP) supplementation with 0.1% glycine and 0.3% proline; FY) supplementation with 0.2% phenylalanine and 0.2% tyrosine; MKT) supplementation with 0.62% lysine, 0.22% methionine and 0.61% threonine. For statistical analysis, t-test was used to compare AA-supplemented animals to the Ctrl group. At week 7, body weight and average daily gain (ADG) were measured and blood samples and skeletal muscle biopsies were taken. Blood biochemistry analytes related to energy metabolism were determined and it was shown that MKT group had higher serum creatinine and higher plasma concentration of three supplemented AAs as well as arginine compared with the Ctrl group. GP group had similar glycine/proline plasma concentration compared with the other groups while in FY group only plasma phenylalanine concentration was higher compared with Control. Although the AA supplementations in the GP and FY groups did not affect average daily gain and metabolic health profile from serum, the metabolome analysis from skeletal muscle biopsy revealed several differences between the GP-FY groups and the Ctrl-MKT groups, suggesting a metabolic adaptation especially in GP and FY groupsinfo:eu-repo/semantics/publishedVersio

Microfluidic Organ‐on‐a‐Chip Technology for Advancement of Drug Development and Toxicology

In recent years, the exploitation of phenomena surrounding microfluidics has seen an increase in popularity, as researchers have found a way to use their unique properties to create superior design alternatives. One such application is representing the properties and functions of different organs on a microscale chip for the purpose of drug testing or tissue engineering. With the introduction of “organ‐on‐a‐chip” systems, researchers have proposed various methods on various organ‐on‐a‐chip systems to mimic their in vivo counterparts. In this article, a systematic approach is taken to review current technologies pertaining to organ‐on‐a‐chip systems. Design processes with attention to the particular instruments, cells, and materials used are presented

Raw NMR data for "NMR based metabolomic analysis of the physiological role of the electron-bifurcating FeFe-hydrogenase Hnd in Solidesulfovibrio fructosivorans under pyruvate fermentation"

This dataset contains raw NMR spectra used for the metabolomics study published in "NMR based metabolomic analysis of the physiological role of the electron-bifurcating FeFe-hydrogenase Hnd in Solidesulfovibrio fructosivorans under pyruvate fermentation". Proton NMR spectra of culture medium and cell pellets, from WT and HndD-deleted Solidesulfovibrio fructosivorans strains, grown under pyruvate fermentation condition, were recorded using liquid-state and HRMAS NMR spectroscopy, respectively.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV