The analysis of the skeletal muscle metabolism is crucial for designing optimal exercise paradigms in type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease that commonly results from a high-calorie diet and sedentary lifestyle, leading to insulin resistance and glucose homeostasis perturbation. Physical activity is recommended as one first-line treatment in T2DM, but it leads to contrasted results. We hypothesized that, instead of applying standard exercise protocols, the prescription of personalized exercise programs specifically designed to reverse the potential metabolic alterations in skeletal muscle could result in better results. METHODS: To test this hypothesis, we drew the metabolic signature of the fast-twitch quadriceps muscle, based on a combined unbiased NMR spectroscopy and RT-qPCR study, in several T2DM mouse models of different genetic background (129S1/SvImJ, C57Bl/6J), sex and aetiology (high-fat diet (HFD) or HFD/Streptozotocin (STZ) induction or transgenic MKR (FVB-Tg Ckm-IGF1R*K1003R)1Dlr/J) mice. Three selected mouse models with unique muscular metabolic signatures were submitted to three different swimming-based programs, designed to address each metabolic specificity. RESULTS: We found that depending on the genetic background, the sex, and the mode of T2DM induction, specific muscular adaptations occurred, including depressed glycolysis associated with elevated PDK4 expression, shift to ß-oxidation, or deregulation of amino-acid homeostasis. Interestingly, dedicated swimming-based exercises designed to restore specific metabolic alterations in muscle were found optimal in improving systemic T2DM hallmarks, including a significant reduction in insulin resistance, the improvement of glucose homeostasis, and a delay in sensorimotor function alterations. CONCLUSION: The muscle metabolism constitutes an important clue for the design of precision exercises with potential clinical implications for T2DM patients.

Revisiting the nature and pharmacodynamics of tacrolimus metabolites.

The toxicity of tacrolimus metabolites and their potential pharmacodynamic (PD) interactions with tacrolimus might respectively explain the surprising combination of higher toxicity and lower efficacy of tacrolimus despite normal blood concentrations, described in extensive metabolizers. To evaluate such interactions, we produced tacrolimus metabolites in vitro and characterized them by high resolution mass spectrometry (HRMS, for all) and nuclear magnetic resonance (NMR, for the most abundant, M-I). We quantified tacrolimus metabolites and checked their structure in patient whole blood and peripheral blood mononuclear cells (PBMC). We explored the interactions of M-I with tacrolimus in silico, in vitro and ex vivo. In vitro metabolization produced isoforms of tacrolimus and of its metabolites M-I and M-III, whose HRMS fragmentation suggested an open-ring structure. M-I and M-III open-ring isomers were also observed in patient blood. By contrast, NMR could not detect these open-ring forms. Transplant patients expressing CYP3A5 exhibited higher M-I/TAC ratios in blood and PBMC than non-expressers. Molecular Dynamics simulations showed that: all possible tacrolimus metabolites and isomers bind FKPB12; and the hypothetical open-ring structures induce looser binding between FKBP12 and calcineurins, leading to lower CN inhibition. In vitro, tacrolimus bound FKPB12 with more affinity than purified M-I, and the pool of tacrolimus metabolites and purified M-I had only weak inhibitory activity on IL2 secretion and not at all on NFAT nuclear translocation. M-I showed no competitive effect with tacrolimus on either test. Finally, M-I or the metabolite pool did not significantly interact with tacrolimus MLR suppression, thus eliminating a pharmacodynamic interaction.

One touch is all it takes: the supramolecular interaction between ubiquitin and lanthanide complexes revisited by paramagnetic NMR and molecular dynamics.

The supramolecular interaction between lanthanide complexes and proteins is at the heart of numerous chemical and biological studies. Some of these complexes have demonstrated remarkable interaction properties with proteins or peptides in solution and in the crystalline state. Here we have used the paramagnetism of lanthanide ions to characterize the affinity of two lanthanide complexes for ubiquitin. As the interaction process is dynamic, the acquired NMR data only reflect the time average of the different steps. We have used molecular dynamics (MD) simulations to get a deeper insight into the detailed interaction scenario at the microsecond scale. This NMR/MD approach enabled us to establish that the tris-dipicolinate complex interacts specifically with arginines and lysines, while the crystallophore explores the protein surface through weak interactions with carboxylates. These observations shed new light on the dynamic interaction properties of these complexes, which will ultimately enable us to propose a crystallization mechanism.

Loss of prion protein control of glucose metabolism promotes neurodegeneration in model of prion diseases.

Corruption of cellular prion protein (PrPC) function(s) at the plasma membrane of neurons is at the root of prion diseases, such as Creutzfeldt-Jakob disease and its variant in humans, and Bovine Spongiform Encephalopathies, better known as mad cow disease, in cattle. The roles exerted by PrPC, however, remain poorly elucidated. With the perspective to grasp the molecular pathways of neurodegeneration occurring in prion diseases, and to identify therapeutic targets, achieving a better understanding of PrPC roles is a priority. Based on global approaches that compare the proteome and metabolome of the PrPC expressing 1C11 neuronal stem cell line to those of PrPnull-1C11 cells stably repressed for PrPC expression, we here unravel that PrPC contributes to the regulation of the energetic metabolism by orienting cells towards mitochondrial oxidative degradation of glucose. Through its coupling to cAMP/protein kinase A signaling, PrPC tones down the expression of the pyruvate dehydrogenase kinase 4 (PDK4). Such an event favors the transfer of pyruvate into mitochondria and its conversion into acetyl-CoA by the pyruvate dehydrogenase complex and, thereby, limits fatty acids ß-oxidation and subsequent onset of oxidative stress conditions. The corruption of PrPC metabolic role by pathogenic prions PrPSc causes in the mouse hippocampus an imbalance between glucose oxidative degradation and fatty acids ß-oxidation in a PDK4-dependent manner. The inhibition of PDK4 extends the survival of prion-infected mice, supporting that PrPSc-induced deregulation of PDK4 activity and subsequent metabolic derangements contribute to prion diseases. Our study posits PDK4 as a potential therapeutic target to fight against prion diseases.

NMR metabolomics study of chronic low-dose exposure to a cocktail of persistent organic pollutants.

Nowadays, exposure to endocrine-disrupting chemicals (EDCs), including persistent organic pollutants (POPs), is one of the most critical threats to public health. EDCs are chemicals that mimic, block, or interfere with hormones in the body's endocrine system and have been associated with a wide range of health issues. This innovative, untargeted metabolomics study investigates chronic low-dose internal exposure to a cocktail of POPs on multiple tissues that are known to accumulate these lipophilic compounds. Interestingly, the metabolic response differs among selected tissues/organs in mice. In the liver, we observed a dynamic effect according to the exposure time and the doses of POPs. In the brain tissue, the situation is the opposite, leading to the conclusion that the presence of POPs immediately gives a saturated effect that is independent of the dose and the duration of exposure studied. By contrast, for the adipose tissues, nearly no effect is observed. This metabolic profiling leads to a holistic and dynamic overview of the main metabolic pathways impacted in lipophilic tissues by a cocktail of POPs.

A Toolbox for Glutamine Use in Dissolution Dynamic Nuclear Polarization: from Enzymatic Reaction Monitoring to the Study of Cellular Metabolic Pathways and Imaging.

Glutamine is under scrutiny regarding its metabolic deregulation linked to energetic reprogramming in cancer cells. Many analytical techniques have been used to better understand the impact of the metabolism of amino acids on biological processes, however only a few are suited to work with complex samples. Here, we report the use of a general dissolution dynamic nuclear polarization (D-DNP) formulation using an unexpensive radical as a multipurpose tool to study glutamine, with insights from enzymatic modelling to complex metabolic networks and fast imaging. First, hyperpolarized [5-13 C] glutamine is used as molecular probe to study the kinetic action of two enzymes: L-asparaginase that has been used as an anti-metabolic treatment for cancer, and glutaminase. These results are also compared with those acquired with another hyperpolarized amino acid, [1,4-13 C] asparagine. Second, we explored the use of hyperpolarized (HP) substrates to probe metabolic pathways by monitoring metabolic profiles arising from hyperpolarized glutamine in E. coli extracts. Finally, a highly concentrated sample formulation is proposed for the purpose of fast imaging applications. We think that this approach can be extended to formulate other amino acids as well as other metabolites and provide complementary insights into the analysis of metabolic networks.

Present and future of pure shift NMR in metabolomics.

NMR is one of the most powerful techniques for the analysis of biological samples in the field of metabolomics. However, the high complexity of fluids, tissues, or other biological materials taken from living organisms is still a challenge for state-of-the-art pulse sequences, thereby limiting the detection, the identification, and the quantification of metabolites. In this context, the resolution enhancement provided by broadband homonuclear decoupling methods, which allows for simplifying 1 H multiplet patterns into singlets, has placed this so-called pure shift technique as a promising approach to perform metabolic profiling with unparalleled level of detail. In recent years, the many advances achieved in the design of pure shift experiments has paved the way to the analysis of a wide range of biological samples with ultra-high resolution. This review leads the reader from the early days of the main pure shift methods that have been successfully developed over the last decades to address complex samples, to the most recent and promising applications of pure shift NMR to the field of NMR-based metabolomics.

Ultrahigh-Resolution NMR with Water Signal Suppression for a Deeper Understanding of the Action of Antimetabolic Drugs on Diffuse Large B-Cell Lymphoma.

Ultrahigh-resolution NMR has recently attracted considerable attention in the field of complex samples analysis. Indeed, the implementation of broadband homonuclear decoupling techniques has allowed us to greatly simplify crowded 1H spectra, yielding singlets for almost every proton site from the analyzed molecules. Pure shift methods have notably shown to be particularly suitable for deciphering mixtures of metabolites in biological samples. Here, we have successfully implemented a new pure shift pulse sequence based on the PSYCHE method, which incorporates a block for solvent suppression that is suitable for metabolomics analysis. The resulting experiment allows us to record ultrahigh-resolution 1D NOESY 1H spectra of biofluids with suppression of the water signal, which is a crucial step for highlighting metabolite mixtures in an aqueous phase. We have successfully recorded pure shift spectra on extracellular media of diffuse large B-cell lymphoma (DLBCL) cells. Despite a lower sensitivity, the resolution of pure shift data was found to be better than that of the standard approach, which provides a more detailed vision of the exo-metabolome. The statistical analyses carried out on the resulting metabolic profiles allow us to successfully highlight several metabolic pathways affected by these drugs. Notably, we show that Kidrolase plays a major role in the metabolic pathways of this DLBCL cell line.

Synthesis and characterization of novel conformers of (E)-2-(3-nitro-H-imidazo[1,2-a]pyridin-2-ylthio)-N'-benzylideneacetohydrazide derivatives.

Eighteen new N-acylhydrazones (9a-r) containing the imidazo[1,2-a]pyridine scaffold were synthesized through a seven steps reaction sequence, ending with a condensation of 2-(3-nitro-H-imidazo[1,2-a]pyridin-2-ylthio)acetohydrazide with various benzaldehyde derivatives (8a-r). All synthesized compounds were characterized by 1D NMR (1 H and 13 C NMR) and 2D NMR (NOESY) spectroscopic analyses and high-resolution mass spectrometry (HRMS). The analysis of 1 H NMR data performed at room temperature in deuterated dimethylsulfoxide (DMSO-d6 ) revealed the presence of (E)-2-(3-nitro-H-imidazo[1,2-a]pyridin-2-ylthio)-N'-benzylideneacetohydrazide (9a-r) as a mixture of two conformers, namely, syn-periplanar E (sp E) and anti-periplanar E (ap E). For all N-acylhydrazones that were synthesized, the sp E conformer was found to be the major form except in the case of hydrazone derived from o-hydroxybenzaldehyde.

Structural analysis of unstable norbixin isomers guided by pure shift nuclear magnetic resonance.

We report the analysis of complex samples obtained during the microwave irradiation/heating of norbixin, which has been identified as a potential therapeutic target for age-related macular degeneration (AMD). In this context, identifying the different isomers that are obtained during its degradation is of primary importance. However, this characterization is challenging because, on the one hand, some of these isomers are unstable, and on the other hand, the 1 H spectra of these isomeric mixtures are poorly resolved. We could successfully apply 1D pure shift experiments to obtain ultrahigh-resolution 1 H nuclear magnetic resonance (NMR) spectra of the norbixin isomer samples and exploit their information content to analyze complementary 2D NMR data and describe accurately their isomeric composition.

On the Supra-LUMO Interaction: Case Study of a Sudden Change of Electronic Structure as a Functional Emergence.

The synergistic functioning of redox-active components that emerges from prototypical 2,2'-di(N-methylpyrid-4-ylium)-1,1'-biphenyl is described. Interestingly, even if a trans conformation of the native assembly is expected, due to electrostatic repulsion between cationic pyridinium units, we demonstrate that cis conformation is equally energy-stabilized on account of a peculiar LUMO (SupLUMO) that develops through space, encompassing the two pyridiniums in a single, made-in-one-piece, electronic entity (superelectrophoric behavior). This SupLUMO emergence, with the cis species as superelectrophore embodiment, originates in a sudden change of electronic structure. This finding is substantiated by insights from solid state (single-crystal X-ray diffraction) and solution (NOE NMR and UV-vis-NIR spectroelectrochemistry) studies, combined with electronic structure computations. Electrochemistry shows that electron transfers are so strongly correlated that two-electron reduction manifests itself as a single-step process with a large potential inversion consistent with inner creation of a carbon-carbon bond (digital simulation). Besides, absence of reductive formation of dimers is a further indication of a preferential intramolecular reactivity determined by the SupLUMO interaction (cis isomer pre-organization). The redox-gated covalent bond, serving as electron reservoir, was studied via atropisomerism of the reduction product (VT NMR study). The overall picture derived from this in-depth study of 2,2'-di(N-methylpyrid-4-ylium)-1,1'-biphenyl proves that trans and cis species are worth considered as intrinsically sharply different, that is, as doubly-electrophoric and singly-superelectrophoric switchable assemblies, beyond conformational isomerism. Most importantly, the through-space-mediated SupLUMO may come in complement of other weak interactions encountered in Supramolecular Chemistry as a tool for the design of electroactive architectures.

Endometriosis phenotypes are associated with specific serum metabolic profiles determined by proton-nuclear magnetic resonance.

RESEARCH QUESTION: What is the correlation between serum metabolic profile and endometriosis phenotype? DESIGN: A pilot study nestled in a prospective cohort study at a university hospital, including 46 patients with painful endometriosis who underwent surgery and 21 controls who did not have macroscopic endometriotic lesions. Endometriosis was strictly classified into two groups of 23 patients each: endometrioma (OMA) and deep infiltrating endometriosis (DIE). Serum samples were collected before surgery for metabolomic profiling based on proton-nuclear magnetic resonance spectroscopy in combination with statistical approaches. Comparative identification of the metabolites in the serum from endometriosis patients and from controls was carried out, including an analysis according to endometriosis phenotype. RESULTS: The serum metabolic profiles of the endometriosis patients revealed significantly lower concentrations of several amino acids compared with the controls, whereas the concentrations of free fatty acids and ketone bodies were significantly higher. The OMA and the DIE phenotypes each had a specific metabolic profile, with higher concentrations of two ketone bodies in the OMA group, and higher concentrations of free fatty acids and lipids in the DIE group. CONCLUSION: Proton-nuclear magnetic resonance-based metabolomics of serum samples were found to have ample potential for identifying metabolic changes associated with endometriosis phenotypes. This information may improve our understanding of the pathogenesis of endometriosis.

The follicular fluid metabolome differs according to the endometriosis phenotype.

RESEARCH QUESTION: Is there a follicular fluid-specific metabolic profile in deep infiltrating endometriosis (DIE) depending on the presence of an associated ovarian endometrioma (OMA) that could lead to the identification of biomarkers for diagnosis and prognosis of the disease? DESIGN: In this prospective cohort study, proton nuclear magnetic resonance (1H-NMR) experiments were carried out on 50 follicular fluid samples from patients presenting with DIE, associated or not associated with an OMA, and 29 follicular fluid samples from patients with infertility caused by a tubal obstruction. RESULTS: Concentrations of glucose, citrate, creatine and amino acids such as tyrosine and alanine were lower in women with DIE than control participants, whereas concentrations of lactate, pyruvate, lipids and ketone bodies were higher. Metabolic analysis revealed enhanced concentrations of glycerol and ketone bodies in patients with OMA, indicative of an activation of lipolysis followed by beta-oxidation. Concentrations of lactate and pyruvate were increased in patients without OMA, whereas the concentration of glucose was decreased, highlighting activation of the anaerobic glycolysis pathway. Differences in concentrations of amino acids such as threonine and glutamine were also statistically relevant in discriminating between the presence or absence of OMA. CONCLUSIONS: Results indicate a mitochondrial dysregulation in endometriosis phenotypes, with a modified balance between anaerobic glycolysis and beta-oxidation in OMA phenotypes that could affect the fertility of women with endometriosis. As the composition of the follicular fluid has been shown to be correlated with oocyte development and outcome of implantation after fertilization, these findings may help explain the high level of infertility in these patients.

Correction to: Urinary metabolic profiling of asymptomatic acute intermittent porphyria using a rule-mining-based algorithm.

The article Urinary metabolic profiling of asymptomatic acute intermittent porphyria using a rule-mining-based algorithm, written by Margaux Luck, Caroline Schmitt, Neila Talbi, Laurent Gouya, Cédric Caradeuc, Hervé Puy, Gildas Bertho and Nicolas Pallet was originally published Online First without open access. After publication in volume [14], issue [1], Citation ID[10] the author decided to opt for Open Choice and to make the article an open access publication. Therefore, the copyright of the article has been changed to © The Author(s) 2018 and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/ ), which permits use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made. The original article has been corrected.

Insights into the interaction of high potency inhibitor IRC-083864 with phosphatase CDC25.

CDC25 phosphatases play a crucial role in cell cycle regulation. They have been found to be over-expressed in various human tumours and to be valuable targets for cancer treatment. Here, we report the first model of binding of the most potent CDC25 inhibitor to date, the bis-quinone IRC-083864, into CDC25B obtained by combining molecular modeling and NMR studies. Our study provides new insights into key interactions of the catalytic site inhibitor and CDC25B in the absence of any available experimental structure of CDC25 with a bound catalytic site inhibitor. The docking model reveals that IRC-083864 occupies both the active site and the inhibitor binding pocket of the CDC25B catalytic domain. NMR saturation transfer difference and WaterLOGSY data indicate the binding zones of the inhibitor and support the docking model. Probing interactions of analogues of the two quinone units of IRC-083864 with CDC25B demonstrate that IRC-083864 competes with each monomer. Proteins 2017; 85:593-601. © 2016 Wiley Periodicals, Inc.

Model of the Interaction between the NF-κB Inhibitory Protein p100 and the E3 Ubiquitin Ligase ß-TrCP based on NMR and Docking Experiments.

NF-κB is a major transcription factor whose activation is triggered through two main activation pathways: the canonical pathway involving disruption of IκB-α/NF-κB complexes and the alternative pathway whose activation relies on the inducible proteolysis of the inhibitory protein p100. One central step controlling p100 processing consists in the interaction of the E3 ubiquitin ligase ß-TrCP with p100, thereby leading to its ubiquitinylation and subsequent either complete degradation or partial proteolysis by the proteasome. However, the interaction mechanism between p100 and ß-TrCP is still poorly defined. In this work, a diphosphorylated 21-mer p100 peptide model containing the phosphodegron motif was used to characterize the interaction with ß-TrCP by NMR. In parallel, docking simulations were performed in order to obtain a model of the 21P-p100/ß-TrCP complex. Saturation transfer difference (STD) experiments were performed in order to highlight the residues of p100 involved in the interaction with the ß-TrCP protein. These results highlighted the importance of pSer865 and pSer869 residues in the interaction with ß-TrCP and particularly the Tyr867 that fits inside the hydrophobe ß-TrCP cavity with the Arg474 guanidinium group. Four other arginines, Arg285, Arg410, Arg431, and Arg521, were found essential in the stabilization of p100 on the ß-TrCP surface. Importantly, the requirement for these five arginine residues of ß-TrCP for the interaction with p100 was further confirmed in vivo, thereby validating the docking model through a biological approach.

Expression in yeast, new substrates, and construction of a first 3D model of human orphan cytochrome P450 2U1: Interpretation of substrate hydroxylation regioselectivity from docking studies.

BACKGROUND: Cytochrome P450 2U1 (CYP2U1) has been identified from the human genome and is highly conserved in the living kingdom. In humans, it has been found to be predominantly expressed in the thymus and in the brain. CYP2U1 is considered as an "orphan" enzyme as few data are available on its physiological function(s) and active site topology. Its only substrates reported so far were unsaturated fatty acids such as arachidonic acid, and, much more recently, N-arachidonoylserotonin. METHODS: We expressed CYP2U1 in yeast Saccharomyces cerevisiae, built a 3D homology model of CYP2U1, screened a library of compounds known to be substrates of CYP2 family with metabolite detection by high performance liquid chromatography-mass spectrometry, and performed docking experiments to explain the observed regioselectivity of the reactions. RESULTS: We show that drug-related compounds, debrisoquine and terfenadine derivatives, subtrates of CYP2D6 and CYP2J2, are hydroxylated by recombinant CYP2U1 with regioselectivities different from those reported for CYP2D6 and 2J2. Docking experiments of those compounds and of arachidonic acid allow us to explain the regioselectivity of the hydroxylations on the basis of their interactions with key residues of CYP2U1 active site. MAJOR CONCLUSION: Our results show for the first time that human orphan CYP2U1 can oxidize several exogenous molecules including drugs, and describe a first CYP2U1 3D model. GENERAL SIGNIFICANCE: These results could have consequences for the metabolism of drugs particularly in the brain. The described 3D model should be useful to identify other substrates of CYP2U1 and help in understanding its physiologic roles.

Urinary metabolic fingerprint of acute intermittent porphyria analyzed by (1)H NMR spectroscopy.

(1)H NMR is a nonbiased technique for the quantification of small molecules that could result in the identification and characterization of potential biomarkers with prognostic value and contribute to better understand pathophysiology of diseases. In this study, we used (1)H NMR spectroscopy to analyze the urinary metabolome of patients with acute intermittent porphyria (AIP), an inherited metabolic disorder of heme biosynthesis in which an accumulation of the heme precursors 5-aminolaevulinic acid (ALA) and porphobilinogen (PBG) promotes sudden neurovisceral attacks, which can be life-threatening. Our objectives were (1) to demonstrate the usefulness of (1)H NMR to identify and quantify ALA and PBG in urines from AIP patients and (2) to identify metabolites that would predict the response to AIP crisis treatment and reflect differential metabolic reprogramming. Our results indicate that (1)H NMR can help to diagnose AIP attacks based on the identification of ALA and PBG. We also show that glycin concentration increases in urines from patients with frequent recurrences at the end of the treatment, after an initial decrease, whereas PBG concentration remains low. Although the reasons for this altered are elusive, these findings indicate that a glycin metabolic reprogramming occurs in AIPr patients and is associated with recurrence. Our results validate the proof of concept of the usefulness of (1)H NMR spectroscopy in clinical chemistry for the diagnosis of acute attack of AIP and identify urinary glycin as a potential marker of recurrence of AIP acute attacks.

Tryptophan depletion and the kinase GCN2 mediate IFN-γ-induced autophagy.

IFN-γ is a master regulator of the immune responses that occur in the transplanted kidney, acting both on the immune system and on the graft itself. The cellular responses to IFN-γ are complex, and emerging evidence suggests that IFN-γ may regulate autophagic functions. Conversely, autophagy modulates innate and adaptive immune functions in various contexts. In this study, we identify a novel mechanism by which IFN-γ activates autophagy in human kidney epithelial cells and provide new insights into how autophagy regulates immune functions in response to IFN-γ. Our results indicate that IFN-γ promotes tryptophan depletion, activates the eIF2α kinase general control nonderepressible-2 (GCN2), and leads to an increase in the autophagic flux. Further, tryptophan supplementation and RNA interference directed against GCN2 inhibited IFN-γ-induced autophagy. This process is of functional relevance because autophagy regulates the secretion of inflammatory cytokines and growth factors by human kidney epithelial cells in response to IFN-γ. These findings assign to IFN-γ a novel function in the regulation of autophagy, which, in turn, modulates IFN-γ-induced secretion of inflammatory cytokines.

Phytochemical Study of the Anthelminthic Potential of Guadeloupean Plant Biodiversity.

Gastrointestinal parasitism is a major health and welfare problem in ruminants. Synthetic chemical anthelmintic drugs have led to the emergence of resistance in gastrointestinal strongyles, inducing the search for alternatives to control the infections that affect ruminants. The objective of this work was to evaluate the anthelmintic potential of plant extracts against Haemonchus contortus Rudolphi. Three plants of the Guadeloupean biodiversity, Momordica charantia L., Carica papaya L. and Sargassum spp., were selected based on their high polyphenolic content and natural abundance. The phytochemistry of plants was explored, a biological assay against the parasite H. contortus was carried out, and several hypotheses about the way of action were proposed by an innovative electrochemical screening method.