Florence Souard

Department of Pharmacotherapy and Pharmaceutics (DPP)

RESEARCH ACTIVITIES

The research activities cover two areas. 

The first one concerns clinical notions and the exploration of interactions between plants and conventional drugs on the basis of the HEDRINE database. HEDRINE is a tool for advising health professionals about interactions to help them make good choices and for a better management of patient. 

The other part concerns more fondamental aspects of metabolomics of based on plants and in particular the modification of the metabolome between plant products (phytomedecine / food supplements) absorbed per os and the fraction that has passed the digestive barrier. 

Selected publications

Articles dans des revues avec comité de lecture

A paraître

Workflow4Metabolomics (W4M): a user-friendly metabolomics platform for analysis of MS and NMR data

Comparison between ZenoTOF 7600 system and QTOF for plant metabolome: an example of metabolomics applied to coffee leaves

2025

Workflow4Metabolomics (W4M): A User-Friendly Metabolomics Platform for Analysis of Mass Spectrometry and Nuclear Magnetic Resonance Data.

Various spectrometric methods can be used to conduct metabolomics studies. Nuclear magnetic resonance (NMR) or mass spectrometry (MS) coupled with separation methods, such as liquid or gas chromatography (LC and GC, respectively), are the most commonly used techniques. Once the raw data have been obtained, the real challenge lies in the bioinformatics required to conduct: (i) data processing (including preprocessing, normalization, and quality control); (ii) statistical analysis for comparative studies (such as univariate and multivariate analyses, including PCA or PLS-DA/OPLS-DA); (iii) annotation of the metabolites of interest; and (iv) interpretation of the relationships between key metabolites and the relevant phenotypes or scientific questions to be addressed. Here, we will introduce and detail a stepwise protocol for use of the Workflow4Metabolomics platform (W4M), which provides user-friendly access to workflows for processing of LC-MS, GC-MS, and NMR data. Those modular and extensible workflows are composed of existing standalone components (e.g., XCMS and CAMERA packages) as well as a suite of complementary W4M-implemented modules. This tool suite is accessible worldwide through a web interface and is hosted on UseGalaxy France. The extensible Virtual Research Environment (VRE) provided offers pre-configured workflows for metabolomics communities (platforms, end users, etc.), as well as possibilities for sharing among users. By providing a consistent ecosystem of tools and workflows through Galaxy, W4M makes it possible to process MS and NMR data from hundreds of samples using an ordinary personal computer, after step-by-step workflow optimization. © 2025 Wiley Periodicals LLC. Basic Protocol 1: W4M account creation, working history preparation, and data upload Support Protocol 1: How to prepare an NMR zip file Support Protocol 2: How to convert MS data from proprietary format to open format Support Protocol 3: How to get help with W4M (IFB forum) and how to report a problem on the GitHub repository Basic Protocol 2: LC-MS data processing Alternate Protocol 1: GC-MS data processing Alternate Protocol 2: NMR data processing Basic Protocol 3: Statistical analysis Basic Protocol 4: Annotation of metabolites from LC-MS data Alternate Protocol 3: Annotation of metabolites from NMR data.

2024

BABINE: An original and user-friendly scale for the simple and quick management of herb-drug interactions in clinical practice

Metabolite profiles of green leaves and coffee beans as predictors of coffee sensory quality in Robusta (Coffea canephora) germplasm from the Democratic Republic of the Congo

Research on the chemical composition of coffee beans and its correlation with sensory quality is advancing, but the metabolites in coffee leaves have often been overlooked. This study investigated the metabolite profiles of roasted coffee, green beans, and coffee leaves from 39 C. canephora genotypes through LC-HRMS with an untargeted metabolomics approach. Our results showed that metabolite profiles of roasted coffee, green beans, and coffee leaves can be discriminated based on the coffee's sensory quality. The highest predictive power of coffee sensory quality was achieved with the metabolite profiles of the coffee leaves. Genotypes with varying genetic backgrounds could only be discriminated by the metabolite profiles of the coffee leaves. Metabolite marker compounds predictive of sensory quality were a putative quercetin derivate in green beans and likely physagulin E and argophyllin in coffee leaves. Estimated levels of caffeoylquinic acids, dicaffeoylquinic acids, and caffeoylquinic acid lactones were higher in roasted coffee with a lower sensory quality. These differences were not apparent in their respective green beans and coffee leaves. Overall, our study revealed the promising potential of the metabolite profile of coffee leaves as a predictive tool for coffee sensory quality and the genetic background of C. canephora.

Metabolite profiles of green leaves and coffee beans as predictors of coffee sensory quality in Robusta (Coffea canephora) germplasm from the Democratic Republic of the Congo

Research on the chemical composition of coffee beans and its correlation with sensory quality is advancing, but the metabolites in coffee leaves have often been overlooked. This study investigated the metabolite profiles of roasted coffee, green beans, and coffee leaves from 39 C. canephora genotypes through LC-HRMS with an untargeted metabolomics approach. Our results showed that metabolite profiles of roasted coffee, green beans, and coffee leaves can be discriminated based on the coffee's sensory quality. The highest predictive power of coffee sensory quality was achieved with the metabolite profiles of the coffee leaves. Genotypes with varying genetic backgrounds could only be discriminated by the metabolite profiles of the coffee leaves. Metabolite marker compounds predictive of sensory quality were a putative quercetin derivate in green beans and likely physagulin E and argophyllin in coffee leaves. Estimated levels of caffeoylquinic acids, dicaffeoylquinic acids, and caffeoylquinic acid lactones were higher in roasted coffee with a lower sensory quality. These differences were not apparent in their respective green beans and coffee leaves. Overall, our study revealed the promising potential of the metabolite profile of coffee leaves as a predictive tool for coffee sensory quality and the genetic background of C. canephora.

Targeted metabolomics and transcript profiling of methyltransferases in three coffee species

Coffee plants contain well-known xanthines as caffeine. Three Coffea species grown in a controlled greenhouse environment were the focus of this research. Coffea arabica and C. canephora are two first principal commercial species and commonly known as arabica and robusta, respectively. Originating in Central Africa, C. anthonyi is a novel species with small leaves. The xanthine metabolites in flower, fruit and leaf extracts were compared using both targeted and untargeted metabolomics approaches. We evaluated how the xanthine derivatives and FQA isomers relate to the expression of biosynthetic genes encoding N- and O-methyltransferases. Theobromine built up in leaves of C. anthonyi because caffeine biosynthesis was hindered in the absence of synthase gene expression. Despite this, green fruits expressed these genes and they produced caffeine. Given that C. anthonyi evolved successfully over time, these findings put into question the defensive role of caffeine in leaves. An overview of the histolocalisation of xanthines in the different flower parts of Coffea arabica was also provided. The gynoecium contained more theobromine than the flower buds or petals. This could be attributed to increased caffeine biosynthesis before fructification. The presence of theophylline and the absence of theobromine in the petals indicate that caffeine is catabolized more in the petals than in the gynoecium.

Targeted metabolomics and transcript profiling of methyltransferases in three coffee species

Xanthines are the most known alkaloids present in coffee plants. The studies about their metabolism and their pharmacological activities have started several years ago to provide more information about the chemical properties of the most popular beverages in the world, such as coffee or tea. This work consisted in performing metabolomic analysis based on LC-(HR)MS data to investigate the metabolism of xanthines in the leaves and in the fruits of Coffea anthonyi, Coffea arabica and Coffea canephora. While C. arabica and C. canephora have been widely studied, only few information is available for C. anthonyi. However, due to the wide climate changes, this species growing at low altitudes could be a promising species to make coffee beverages. The expression of genes for proteins involved in xanthines biosynthesis has also been investigated by performing RT-qPCR. An overview of the histolocalisation of xanthines in the different organs of Coffea arabica flowers was also provided.

No reliable clinical results without a proper description of medicinal herbs

Aromatherapy and cystic fibrosis: real-life, but many questions remain.

2023

Cancer patients' behaviors and attitudes toward natural health products.

Natural health products (NHPs), including vitamins, minerals, and herbal supplements, are the most common complementary and alternative medicine (CAM) among cancer patients. Our survey determined the attitudes and behaviors of cancer patients toward natural complementary therapies that should be considered to implement an integrative approach in the future.

1457 Kampo traditional ointments for wound healing

Kampo herbal ointments for skin wound healing

The management of skin wound healing problems is a public health issue in which traditional herbal medicines could play a determining role. Kampo medicine, with three traditionally used ointments, provides interesting solutions for these dermatological issues. These ointments named Shiunkō , Chuōkō , and Shinsen taitsukō all have in common a lipophilic base of sesame oil and beeswax from which herbal crude drugs are extracted according to several possible manufacturing protocols. This review article brings together existing data on metabolites involved in the complex wound healing process. Among them are representatives of the botanical genera Angelica , Lithospermum , Curcuma , Phellodendron , Paeonia , Rheum , Rehmannia , Scrophularia , or Cinnamomum . Kampo provides numerous metabolites of interest, whose content in crude drugs is very sensitive to different biotic and abiotic factors and to the different extraction protocols used for these ointments. If Kampo medicine is known for its singular standardization, ointments are not well known, and research on these lipophilic formulas has not been developed due to the analytical difficulties encountered in biological and metabolomic analysis. Further research considering the complexities of these unique herbal ointments could contribute to a rationalization of Kampo's therapeutic uses for wound healing.

2022

Herb-anticancer drug interactions in real life based on VigiBase, the WHO global database

Cancer patients could combine herbal treatments with their chemotherapy. We consulted VigiBase, a WHO database of individual case safety reports (ICSRs) which archives reports of suspected Adverse Drug Reactions (ADRs) when herbal products are used in conjunction with anti-cancer treatment. We focused on the possible interactions between antineoplastic (L01 ATC class) or hormone antagonists (L02B ATC class) with 10 commonly used herbs (pineapple, green tea, cannabis, black cohosh, turmeric, echinacea, St John's wort, milk thistle and ginger) to compare ADRs described in ICSRs with the literature. A total of 1057 ICSRs were extracted from the database but only 134 were complete enough (or did not concern too many therapeutic lines) to keep them for analysis. Finally, 51 rationalizable ICSRs could be explained, which led us to propose a pharmacokinetic or pharmacodynamic interaction mechanism. Reports concerned more frequently women and half of the rationalizable ICSRs involved Viscum album and Silybum marianum. 5% of the ADRs described could have been avoided if clinicians had had access to the published information. It is also important to note that in 8% of the cases, the ADRs observed were life threatening. Phytovigilance should thus be considered more by health care professionals to best treat cancer patients and for better integrative care.

Targeted and Untargeted Mass Spectrometry-Based Metabolomics for Chemical Profiling of Three Coffee Species

While coffee beans have been studied for many years, researchers are showing a growing interest in coffee leaves and by-products, but little information is currently available on coffee species other than Coffea arabica and Coffea canephora. The aim of this work was to perform a targeted and untargeted metabolomics study on Coffea arabica, Coffea canephora and Coffea anthonyi. The application of the recent high-resolution mass spectrometry-based metabolomics tools allowed us to gain a clear overview of the main differences among the coffee species. The results showed that the leaves and fruits of Coffea anthonyi had a different metabolite profile when compared to the two other species. In Coffea anthonyi, caffeine levels were found in lower concentrations while caffeoylquinic acid and mangiferin-related compounds were found in higher concentrations. A large number of specialized metabolites can be found in Coffea anthonyi tissues, making this species a valid candidate for innovative healthcare products made with coffee extracts.

HDI Highlighter, The First Intelligent Tool to Screen the Literature on Herb-Drug Interactions

Herbal food supplements are commonly used and can be an important part of patient self-care. Like all other bio-active and therapeutic products, they have a benefit/risk balance. These products are not without adverse effects and potentially interact with other therapies. Educating patients and providing information for health professionals about the risk of herb-drug interactions is key. One of the purposes of the biomedical literature is to inform prescribers. Scientific literature accessible on databases such as PubMed is dense and careful reading is time consuming. We propose a reading aid tool named “HDI highlighter” to help readers to find key information in clinical studies and case reports describing herb-drug interactions. It uses natural language processing algorithms (artificial intelligence) with a pharmaceutical focus. Semantic relation extraction for herb-drug interactions from the biomedical literature are overexpressed using keywords. We have tested it to review 120 published articles over the last 10 years. In these articles, we have shown that case reports often involved long-term or semi-long-term treatments such as cancer or human immunodeficiency virus therapies, antiepileptic drugs, or central nervous system drugs. Similarly, these classes of drugs are more extensively targeted by clinical studies. Herb-drug interactions described in case reports are identified in medicinal, recreational, and alimentary uses. They also usually lack a rigorous description of the herb(s) involved. Typically, clinical studies provide a complete description of protocols and dosages, with a few exceptions explained by patients' needs. Clinical studies on herbs are nevertheless conducted on a limited number of patients. All these limitations make the interpretation of herb-drug interactions complicated, but the HDI highlighter provides a quick overview of the herb-drug interaction literature.

2021

Coffee Leaves: An Upcoming Novel Food?

Unlike those of coffee beans, the healthy properties of coffee leaves have been overlooked for a long time, even if they are consumed as a beverage by local communities of several African countries. Due to the presence of xanthines, diterpenes, xanthones, and several other polyphenol derivatives as main secondary metabolites, coffee leaves might be useful to prevent many daily disorders. At the same time, as for all bioactive molecules, careless use of coffee leaf infusions may be unsafe due to their adverse effects, such as the excessive stimulant effects on the central nervous system or their interactions with other concomitantly administered drugs. Moreover, the presence of some toxic diterpene derivatives requires careful analytical controls on manufactured products made with coffee leaves. Accordingly, knowledge about the properties of coffee leaves needs to be increased to know if they might be considered a good source for producing new supplements. The purpose of the present review is to highlight the biosynthesis, metabolism, and distribution of the 4 main classes of secondary metabolites present in coffee leaves, their main pharmacological and toxicological aspects, and their main roles in planta. Differences in coffee leaf chemical composition depending on the coffee species will also be carefully considered.

Untargeted metabolomics approach to discriminate mistletoe commercial products

Proposals for Antimicrobial Testing Guidelines Applied on Ajowan and Spanish Lavender Essential Oils

Abstract To fight the rising resistance of microorganisms to antibiotics, a strategy followed by several researchers is to focus on natural compounds, such as essential oils, as a source of potent antibacterial compounds. These last decades, hundreds of original papers have been written about microbiological assays that prove the antibacterial activity of essential oils and their use in the medical field. But can we really compare all the data available in the literature when the raw material, the microbiological assays, and/or the strains are different from one article to another? This review will point out the differences and the inadequate practices found in published articles that tested 2 lesser-studied essential oils-Spanish lavender and the ajowan-by the broth dilution method against Staphylococcus aureus, a human pathogenic bacterium. Many pitfalls were found in the literature, for example, a variable chemical composition rarely underlined by the authors, unidentified strains or clinical strains used without a related antibiogram, a lack of quality controls, and the assertion of questionable positive results. At last, some general guidelines that should be followed by every scientific researcher will be discussed.

Antibacterial Activities of Homemade Matrices Miming Essential Oils Compared to Commercial Ones

The increasing bacterial resistance to antibiotics is a worldwide concern. Essential oils are known to possess remarkable antibacterial properties, but their high chemical variability complicates their development into new antibacterial agents. Therefore, the main purpose of this study was to standardize their chemical composition. Several commercial essential oils of ajowan (Trachyspermum ammi L.) and thyme (chemotype thymol) (Thymus vulgaris L.) were bought on the market. GC-MS analysis revealed that thyme essential oils have a chemical composition far more consistent than ajowan essential oils. Sometimes thymol was not even the major compound. The most abundant compounds and the homemade mixtures were tested against two Staphylococcus aureus strains. The antibacterial property of β-caryophyllene presented no direct activity against S. aureus LMG 15975, but in association with thymol or carvacrol at equal percentages an MIC of 125 μg/mL was observed. The mixture of those three compounds at equivalent percentages also decreased by 16-fold the MIC of the penicillin V. Against S. aureus LMG 21674, β-caryophyllene presented an MIC of 31.3 μg/mL and decreased by 267-fold the MIC of the penicillin V. These observations led us to question the benefits of using a complex chemical mixture instead of one active compound to fight bacterial resistance.

Does the Phytochemical Diversity of Wild Plants Like the Erythrophleum genus Correlate with Geographical Origin?

Secondary metabolites are essential for plant survival and reproduction. Wild undomesticated and tropical plants are expected to harbor highly diverse metabolomes. We investigated the metabolomic diversity of two morphologically similar trees of tropical Africa, Erythrophleum suaveolens and E. ivorense, known for particular secondary metabolites named the cassaine-type diterpenoids. To assess how the metabolome varies between and within species, we sampled leaves from individuals of different geographic origins but grown from seeds in a common garden in Cameroon. Metabolites were analyzed using reversed phase LC-HRMS(/MS). Data were interpreted by untargeted metabolomics and molecular networks based on MS/MS data. Multivariate analyses enabled us to cluster samples based on species but also on geographic origins. We identified the structures of 28 cassaine-type diterpenoids among which 19 were new, 10 were largely specific to E. ivorense and five to E. suaveolens. Our results showed that the metabolome allows an unequivocal distinction of morphologically-close species, suggesting the potential of metabolite fingerprinting for these species. Plant geographic origin had a significant influence on relative concentrations of metabolites with variations up to eight (suaveolens) and 30 times (ivorense) between origins of the same species. This shows that the metabolome is strongly influenced by the geographical origin of plants (i.e., genetic factors).

2020

Antibacterial and Cytotoxic Activities of Ten Commercially Available Essential Oils

Two in one: bifunctional derivatives of trolox acting as antimalarial and antioxidant agents

Background: The aim of the present work was to set-up compounds that are able to act simultaneously as antimalarial and antioxidants. Trolox, a known antioxidant was chosen as a core structure to ensure the antioxidant activity and contribute to antiplasmodial effect. Results: Ten compounds were prepared in one step and evaluated on chloroquino-sensitive (3D7) and chloroquino-resistant (FcB1) strains of Plasmodium falciparum. The most active compound (3d) shows antiplasmodial activity in the range of chloroquine against chloroquino-sensitive and chloroquino-resistant P. falciparum strain. The antioxidant activity of (3d) was conducted through four tests and was found to be more potent than trolox itself and L-ascorbic acid. Conclusion: Compound (3d) can be considered as an excellent lead molecule for further in vivo studies. This study paves the way for building large chemical libraries to be investigated in the field of malaria.

Mistletoe-Extract Drugs Stimulate Anti-Cancer Vγ9Vδ2 T Cells.

Human phosphoantigen-reactive Vγ9Vδ2 T cells possess several characteristics, including MHC-independent recognition of tumor cells and potent killing potential, that make them attractive candidates for cancer immunotherapeutic approaches. Injectable preparations from the hemi-parasite plant Viscum album L. (European mistletoe) are commonly prescribed as complementary cancer therapy in European countries such as Germany, but their mechanism of action remains poorly understood. Here, we investigated in-depth the in vitro response of human T cells towards mistletoe-extract drugs by analyzing their functional and T-cell-receptor (TCR) response using flow cytometry and high-throughput sequencing respectively. Non-fermented mistletoe-extract drugs (AbnobaViscum), but not their fermented counterparts (Iscador), induced specific expansion of Vγ9Vδ2 T cells among T cells. Furthermore, AbnobaViscum rapidly induced the release of cytotoxic granules and the production of the cytokines IFNγ and TNFα in Vγ9Vδ2 T cells. This stimulation of anti-cancer Vγ9Vδ2 T cells was mediated by the butyrophilin BTN3A, did not depend on the accumulation of endogenous phosphoantigens and involved the same Vγ9Vδ2 TCR repertoire as those of phosphoantigen-reactive Vγ9Vδ2 T cells. These insights highlight Vγ9Vδ2 T cells as a potential target for mistletoe-extract drugs and their role in cancer patients receiving these herbal drugs needs to be investigated.

A new potential anti‐cancer beta‐carboline derivative decreases the expression levels of key proteins involved in glioma aggressiveness: A proteomic investigation

Gliomas remain highly fatal due to their high resistance to current therapies. Deregulation of protein synthesis contributes to cancer onset and progression and is a source of rising interest for new drugs. CM16, a harmine derivative with predicted high blood-brain barrier penetration, exerts antiproliferative effects partly through translation inhibition. We evaluated herein how CM16 alters the proteome of glioma cells. The analysis of the gel-free LC/MS and auto-MS/MS data showed that CM16 induces time- and concentration-dependent significant changes in the total ion current chromatograms. In addition, we observed spontaneous clustering of the samples according to their treatment condition and their proper classification by unsupervised and supervised analyses, respectively. A two-dimensional gel-based approach analysis allowed us to identify that treatment with CM16 may downregulate four key proteins involved in glioma aggressiveness and associated with poor patient survival (HspB1, BTF3, PGAM1, and cofilin), while it may upregulate galectin-1 and Ebp1. Consistently with the protein synthesis inhibition properties of CM16, HspB1, Ebp1, and BTF3 exert known roles in protein synthesis. In conclusion, the downregulation of HspB1, BTF3, PGAM1 and cofilin bring new insights in CM16 antiproliferative effects, further supporting CM16 as an interesting protein synthesis inhibitor to combat glioma.

2018

Determination of three main chlorogenic acids in water extracts of coffee leaves by liquid chromatography coupled to an electrochemical detector

Coffee is a beverage widely consumed in the world. The coffee species most commercialized worldwide are Arabica (Coffea arabica) and Robusta (Coffea canephora). Roasted coffee beans are the most used, but coffee leaves are also consumed as infusion in several countries for traditional medicinal purposes. They contain several interesting phenolic antioxidant compounds mainly belonging to chlorogenic acids (CGAs). In the present work, a liquid chromatography-electrochemical detection (LC-EC) method was developed for the determination of three main chlorogenic acid isomers, namely 3-, 4-, and 5-caffeoylquinic acids (CQA), in coffee leaves aqueous extracts. Samples from eight coffee species, namely; Coffea arabica, Coffea canephora, Coffea liberica, Coffea humilis, Coffea mannii, Coffea charrieriana, Coffea anthonyi, and Coffea liberica var. liberica, were grown and collected in tropical greenhouses. Linearity of the calibration graphs was observed in the range from the limit of quantification to 1.0 × 10−5 M, with R2 equal to 99.9% in all cases. High sensitivity was achieved with a limit of detection of 1.0 × 10−8 M for 3-CQA and 5-CQA (i.e., 3.5 µg/L) and 2.0 × 10−8 M for 4-CQA (i.e., 7.1 µg/L). The chromatographic profile of the samples harvested for each Coffea species was studied comparatively. Obtained raw data were pretreated for baseline variations and shifts in retention times between the chromatographic profiles. Principal Component Analysis (PCA) was applied to the pretreated data. According to the results, three clusters of Coffea species were found. In the water sample extracts, 5-CQA appeared to be the major isomer, and some species contained a very low amount of CQAs. Fluctuations were observed depending on the Coffea species and harvesting period. Significant differences between January and July were noticed regarding CQAs content. The species with the best CQAs/caffeine ratio was identified. The LC-EC data were validated by liquid chromatography-high resolution mass spectrometry (LC-HRMS).

Metabolomics fingerprint of coffee species determined by untargeted-profiling study using LC-HRMS

Coffee bean extracts are consumed all over the world as beverage and there is a growing interest in coffee leaf extracts as food supplements. The wild diversity in Coffea (Rubiaceae) genus is large and could offer new opportunities and challenges. In the present work, a metabolomics approach was implemented to examine leaf chemical composition of 9 Coffea species grown in the same environmental conditions. Leaves were analyzed by LC-HRMS and a comprehensive statistical workflow was designed. It served for univariate hypothesis testing and multivariate modeling by PCA and partial PLS-DA on the Workflow4Metabolomics infrastructure. The first two axes of PCA and PLS-DA describes more than 40% of variances with good values of explained variances. This strategy permitted to investigate the metabolomics data and their relation with botanic and genetic informations. Finally, the identification of several key metabolites for the discrimination between species was further characterized.

Identification of coffee leaves using FT-NIR spectroscopy and SIMCA

Abundant literature has been devoted to coffee beans (green or roasted) chemical description but relatively few studies have been devoted to coffee leaves. Given the fact that coffee leaves are used for food and medicinal consumption, it was of interest to develop a rapid screening method in order to identify coffee leaves taxa. Investigation by Fourier - Transform near infrared spectroscopy (FT-NIRS) was performed on nine Coffea taxa leaves harvested over one year in a tropical greenhouse of the Botanic Garden Meise (Belgium). The only process after leaves harvesting was an effective drying and a homogeneous leaves grinding. FT-NIRS with SIMCA analysis allowed to discriminate the spectral profiles across taxon, aging stage (mature and senescence coffee leaves) and harvest period. This study showed that it was possible (i) to classify the different taxa, (ii) to identify their aging stage and (iii) to identify the harvest period for the mature stage with a correct classification rate of 99%, 100% and 90%, respectively.

Contrasting cadmium resistance strategies in two metallicolous populations of Arabidopsis halleri.

While cadmium (Cd) tolerance is a constitutive trait in the Arabidopsis halleri species, Cd accumulation is highly variable. Recent adaptation to anthropogenic metal stress has occurred independently within the genetic units of A. halleri and the evolution of different mechanisms involved in Cd tolerance and accumulation has been suggested. To gain a better understanding of the mechanisms underlying Cd tolerance and accumulation in A. halleri, ionomic inductively coupled plasma mass spectrometry (ICP-MS), transcriptomic (RNA sequencing) and metabolomic (high-performance liquid chromatography-mass spectrometry) profiles were analysed in two A. halleri metallicolous populations from different genetic units (PL22 from Poland and I16 from Italy). The PL22 and I16 populations were both hypertolerant to Cd, but PL22 hyperaccumulated Cd while I16 behaved as an excluder both in situ and when grown hydroponically. The observed hyperaccumulator vs excluder behaviours were paralleled by large differences in the expression profiles of transporter genes. Flavonoid-related transcripts and metabolites were strikingly more abundant in PL22 than in I16 shoots. The role of novel A. halleri candidate genes possibly involved in Cd hyperaccumulation or exclusion was supported by the study of corresponding A. thaliana knockout mutants. Taken together, our results are suggestive of the evolution of divergent strategies for Cd uptake, transport and detoxification in different genetic units of A. halleri.

2017

Terpenoids from Platostoma rotundifolium (Briq.) A. J. Paton Alter the Expression of Quorum Sensing-Related Virulence Factors and the Formation of Biofilm in Pseudomonas aeruginosa PAO1.

Platostoma rotundifolium (Briq.) A. J. Paton aerial parts are widely used in Burundi traditional medicine to treat infectious diseases. In order to investigate their probable antibacterial activities, crude extracts from P. rotundifolium were assessed for their bactericidal and anti-virulence properties against an opportunistic bacterial model, Pseudomonas aeruginosa PAO1. Whereas none of the tested extracts exert bacteriostatic and/or bactericidal proprieties, the ethyl acetate and dichloromethane extracts exhibit anti-virulence properties against Pseudomonas aeruginosa PAO1 characterized by an alteration in quorum sensing gene expression and biofilm formation without affecting bacterial viability. Bioguided fractionation of the ethyl acetate extract led to the isolation of major anti-virulence compounds that were identified from nuclear magnetic resonance and high-resolution molecular spectroscopy spectra as cassipourol, β-sitosterol and α-amyrin. Globally, cassipourol and β-sitosterol inhibit quorum sensing-regulated and -regulatory genes expression in las and rhl systems without affecting the global regulators gacA and vfr, whereas α-amyrin had no effect on the expression of these genes. These terpenoids disrupt the formation of biofilms at concentrations down to 12.5, 50 and 50 µM for cassipourol, β-sitosterol and α-amyrin, respectively. Moreover, these terpenoids reduce the production of total exopolysaccharides and promote flagella-dependent motilities (swimming and swarming). The isolated terpenoids exert a wide range of inhibition processes, suggesting a complex mechanism of action targeting P. aeruginosa virulence mechanisms which support the wide anti-infectious use of this plant species in traditional Burundian medicine.

Responses of above- and below-ground fungal symbionts to cessation of mowing in subalpine grassland

The cessation of mowing in subalpine grasslands promotes the dominance of Festuca paniculata leading to the reduction in plant diversity. Moreover, it affects positively the abundance of Epichloë sp. inhabiting F. paniculata leaves and negatively the soil density of arbuscular mycorrhizal fungi (AMF). We explored how the cessation of mowing influences root AMF communities in F. paniculata and the neighboring plants, and Epichloë sp alkaloids. Thirteen AMF operational taxonomical units were found. The neighboring plants affected positively the abundances of Aalpin and GLOM_7 whereas the interaction plant/management type influenced significantly Claroide_1, GLOM_1 and GLOM_7. The N-formylnorloline, produced by Epichloë sp. increased in unmown grassland. Hence, the cessation of mowing, coinciding with the high abundance of endophyte alkaloid, affected root-associated AMF with differential responses at the abundance level. The N-formylnorloline could be one compound underpinning the dynamic of plant diversity with a resulting structuration of AMF in subalpine grasslands.

2015

Optimization of Experimental Parameters to Explore Small-Ligand/Aptamer Interactions through Use of (1) H NMR Spectroscopy and Molecular Modeling.

Aptamers constitute an emerging class of molecules designed and selected to recognize any given target that ranges from small compounds to large biomolecules, and even cells. However, the underlying physicochemical principles that govern the ligand-binding process still have to be clarified. A major issue when dealing with short oligonucleotides is their intrinsic flexibility that renders their active conformation highly sensitive to experimental conditions. To overcome this problem and determine the best experimental parameters, an approach based on the design-of-experiments methodology has been developed. Here, the focus is on DNA aptamers that possess high specificity and affinity for small molecules, L-tyrosinamide, and adenosine monophosphate. Factors such as buffer, pH value, ionic strength, Mg(2+) -ion concentration, and ligand/aptamer ratio have been considered to find the optimal experimental conditions. It was then possible to gain new insight into the conformational features of the two ligands by using ligand-observed NMR spectroscopic techniques and molecular mechanics.

2014

Use of a fractional factorial design to study the effects of experimental factors on the chitin deacetylation.

Chitosan is obtained by deacetylation of chitin. Chitosan versatility is directly related to the polymer's characteristics depending on the deacetylation process. The aim of this research was to study the parameters influencing deacetylation and to elucidate their effect on acetylation degree (DA) and molecular weight (MW). The effect on chitosan DA was investigated using a fractional factorial design 2(7-3) with seven factors and two variation levels. The tested factors were: X1=number of successive baths, X2=reaction time, X3=temperature, X4=alkali reagent, X5=sodium borohydride, X6=the atmospheric conditions and X7=alkali concentration. A mathematical model was investigated corresponding to the following relation ŷ=7.469-1.344X1-1.094X2-3.094X3+1.906X4+0.656X5+0.906X6-1.031X7+0.469X1X2-0.781X3X4+0.906X1X3X4 with R2=0.99. This model allows fixing experimental conditions for each desired DA. To study the effect on chitosan MW, only atmospheric conditions and use of sodium borohydride as an oxygen scavenger were investigated. The use of sodium borohydride and nitrogen atmosphere was found to have a protective effect against chitosan degradation during deacetylation.

HEDRINE : un nouvel outil d'aide à la décision pour les interactions plante-médicament

2013

Occurrence of the synthetic analgesic tramadol in an African medicinal plant.

Pro-oxidant properties of indolone-N-oxides in relation to their antimalarial properties.

Indolone-N-oxides (INODs) are bioreducible and possess remarkable anti-malarial activities in the low nanomolar range in vitro against different Plasmodium falciparum (P. falciparum) strains and in vivo. INODs have an original mechanism of action: they damage the host cell membrane without affecting non-parasitized erythrocytes. These molecules produce a redox signal which activates SYK tyrosine kinases and induces a hyperphosphorylation of AE1 (band 3, erythrocyte membrane protein). The present work aimed to understand the early stages of the biochemical interactions of these compounds with some erythrocyte components from which the redox signal could originate. The interactions were studied in a biomimetic model and compared with those of chloroquine and artemisinin. The results showed that INODs i) do not enter the coordination sphere of the metal in the heme iron complex as does chloroquine; ii) do not generate iron-dependent radicals as does artemisinin; iii) generate stable free radical adducts after reduction at one electron; iv) cannot trap free radicals after reduction. These results confirm that the bioactivity of INODs does not lie in their spin-trapping properties but rather in their pro-oxidant character. This property may be the initiator of the redox signal which activates SYK tyrosine kinases.

Research highlights: African tree gets to the root of pain

β-Cyclodextrin-Glycerol Dimers: Synthesis and NMR Conformational Analysis

The synthesis of new β‐cyclodextrin dimers linked through their primary faces by different glycerol‐like moieties by click chemistry is described. The unusual behaviour of these cyclodextrin-glycerol dimers in aqueous solution has been studied by NMR spectroscopy. We show that, depending on the length of the linking arm between the two cyclodextrins, the dimers could adopt very different conformations in water: symmetrical or pseudo[1]rotaxane‐like structures through one D ‐glucopyranose unit tumbling in one β‐cyclodextrin.

Potential of autochthonous fungal strains isolated from contaminated soils for degradation of polychlorinated biphenyls.

Up to now, most studies on polychlorinated biphenyl (PCB) bioremediation have examined the ability of model fungal strains to biodegrade PCBs. Yet, there is limited information concerning the potential of autochthonous filamentous fungal strains in the biodegradation of PCBs and their possible use in the environmental technologies. In this study, we investigated the capacity of autochthonous fungal strains in the biodegradation of PCBs by isolating 24 taxa from former industrial sites highly contaminated by PCBs. Microscopic and molecular analyses using the internal transcribed spacer (ITS) region revealed that the fungal strains belonged to the phyla Ascomycota (19 strains) and Zygomycota (five strains). The chromatography gas analysis revealed evidence of degradation of seven PCB congeners. With the exception of Circinella muscae which presented no degradation potential, the other fungal strains exhibited a rate of biodegradation ranging from 29 to 85 % after 7 d of incubation in liquid medium. Among these strains, Doratomyces nanus, Doratomyces purpureofuscus, Doratomyces verrucisporus, Myceliophthora thermophila, Phoma eupyrena, and Thermoascus crustaceus showed remarkable degradation ability (>70 %) regardless of the number of chlorine substituents on the biphenyl nucleus and a high tolerance towards PCBs. To our knowledge, this is the first study that demonstrates the ability of PCB degradation by these species and indicates the potential effectiveness of some autochthonous fungal strains in bioremediation systems.

Evaluation of the antiplasmodial activity of extracts of plants used in traditional medicine in Kenya

2012

Sugar-oligoamides: synthesis of DNA minor groove binders.

Sugar-oligoamides have been designed and synthesized as structurally simple carbohydrate-based ligands to study carbohydrate-minor groove DNA interactions. Here we report an efficient solution-phase synthetic strategy to obtain two broad families of sugar-oligoamides. The first type, structure vector A (-Py[Me]-γ-Py-Ind), has a methyl group present as a substituent on the nitrogen of pyrrole B, connected to the C terminal of the oligoamide fragment. The second type, structure vector B (-Py[(CH(2))(11)OH]-γ-Py-Ind), has an alkyl chain present on the nitrogen of pyrrole B connected to the C terminal of the oligoamide fragment and has been designed to access to di- and multivalent sugar-oligoamides. By using sequential DIPC/HOBt coupling reactions, the oligoamide fragment -Py[R]-γ-Py-Ind has been constructed. The last coupling reaction between the anomeric amino sugar and the oligoamide fragment was carried out by activating the acid derivative as a BtO- ester, which has been performed by using TFFH. The isolated esters (BtO-Py[R]-γ-Py-Ind) were coupled with selected amino sugars using DIEA in DMF. The synthesis of two different selective model vectors (vector A (1) and vector B (2)) and two types of water-soluble sugar-oligoamide ligands, with vector A structure (compounds 3-7) and with vector B structure (compound 8), was carried out.

2011

Forming spirocyclohexadienone-oxocarbenium cation species in the biomimetic synthesis of amomols.

The oxidation of appropriate 2-(4-hydroxyphenyl)ethyl ketones gives direct access to amomols by means of the formation of a transient spirocyclohexadienone-oxocarbenium ion that is intermolecularly intercepted by an alcohol. Furthermore, homochiral amomols and other new analogues were synthesized for the first time and were biologically evaluated on Plasmodium falciparum.

Flavonoids as promising lead compounds in type 2 diabetes mellitus: molecules of interest and structure-activity relationship.

There is evidence that hyperglycemia results in the generation of reactive oxygen species, leading to oxidative stress in various tissues, including vascular system. An important link between oxidative stress, inflammatory response and insulin activity is now well established. The ability of antioxidants to protect against the deleterious effects of hyperglycemia and also to improve glucose metabolism and intake must be considered as leads of choice in diabetes treatment. In addition to their antioxidative activity, many flavonoids were demonstrated to act on biological targets involved in type 2 diabetes mellitus such as: α-glycosidase, glucose cotransporter or aldose reductase. In this context, flavonoids behaving as antioxidants were studied as potential drugs by acting as biological targets involved in diabetes development. In this review, we propose to shed light on antioxidants flavonoids investigated as antidiabetics. A special focus was made to address the structure-activity relationship related to the effect of these naturally occurring molecules on different targets involved in diabetes development.

2010

1-Azaaurones derived from the naturally occurring aurones as potential antimalarial drugs.

We report the synthesis and in vitro antiplasmodial activity of 35 compounds, designed as analogues of the naturally occurring aurones. Several of these analogues showed submicromolar antimalarial activity against a chloroquine-resistant strain of Plasmodium falciparum (FcB1-Columbia strain) cultured on human erythrocytes. Substitution of the intracyclic oxygen in aurones by a nitrogen atom and systematic variation of the substituent at the B-ring revealed promising leads showing good activity on the CQ-resistant strain. In particular, 4,6-dimethoxy-4'-ethylazaaurone 22 showed antiplasmodial potency without noticeable toxicity. The easy synthesis of this family of compounds and the relevant antiplasmodial activity are in favor of promising candidates for further development.

2009

A novel chalcone derivative which acts as a microtubule depolymerising agent and an inhibitor of P-gp and BCRP in in-vitro and in-vivo glioblastoma models.

Over the past decades, in spite of intensive search, no significant increase in the survival of patients with glioblastoma has been obtained. The role of the blood-brain barrier (BBB) and especially the activity of efflux pumps belonging to the ATP Binding Cassette (ABC) family may, in part, explain this defect.

2008

Les phénomènes de résistance aux antibiotiques liés aux pompes à efflux : exemple de Staphylococcus aureus.

Efflux pumps located in the bacterial membranes are responsible for low level resistance to antibiotics, considered not to be relevant in the clinic and thus often neglected. However, these pumps contribute to the emergence of high level antibiotic resistance mechanisms, which are responsible for severe complications during the treatment of infectious diseases. Therefore it is necessary to take into account these pumps while developing novel antibacterial agents. Among these new research strategies, the development of efflux pump inhibitors seems to be an attractive approach to restore the activity of some "classical" antibiotics and to limit the emergence of multiresistant strains associated with hospital-acquired infections. In this review, we focalise on Staphylococcus aureus efflux pumps and their potential inhibitors.

Sugar-oligoamides: bound-state conformation and DNA minor-groove-binding description by TR-NOESY and differential-frequency saturation-transfer-difference experiments.

Selective-frequency saturation-transfer-difference (STD) spectra allow the description of complexes established between minor-groove binders and long tracts of calf thymus DNA (ct-DNA). Two sets of experiments with selective saturation of either the H1' or H4'/H5'/H5'' proton NMR regions of deoxyribose allow the description of the ligand residues close to the inner (H1') and outer regions (H4'/H5'/H5'') of the minor groove of double-helical DNA. A series of complexes of sugar-oligoamides (2-6) with ct-DNA have been studied by both TR-NOESY and STD experiments. The binding mode of the complexes is similar to that of netropsin (1) and allows us to define a general binding mode for this family of ligands, in which an NH rim points towards the internal area (inner region) and a CH3 rim points towards the external part (outer region) of the minor groove of DNA. Also by means of both TR-NOESY and STD experiments, a description of the asymmetric centers of the sugar residue close to the inner and outer regions of the groove has been achieved. These results confirm that the sugar is responsible for the differences previously found in binding energetics.

2007

Cyclic Sugar Amino Acids

2006

Isolation and antimalarial activity of alkaloids from Pseudoxandra cuspidata.

A novel and very unusual azaanthracene alkaloid, 1-aza-7,8,9,10-tetramethoxy-4-methyl-2-oxo-1,2-dihydroanthracene ( 1) and a new diastereoisomer of the bis-benzylisoquinoline alkaloid rodiasine, 1 S,1' R-rodiasine ( 2), as well as the alkaloids O-methylpunjabine ( 3) and O-methylmoschatoline ( 4) have been isolated from Pseudoxandra cuspidata bark, used in French Guiana as an antimalarial. Their structures were elucidated by spectroscopic analyses, especially 2D-NMR techniques (ADEQUATE and NOESY). We found that the antimalarial activity of this bark was mostly due to bis-benzylisoquinoline 1 S,1' R-rodiasine ( 2) (IC (50)= 1 microM) also displaying a low cytotoxicity.

2005

Carbohydrate-based DNA ligands: sugar-oligoamides as a tool to study carbohydrate-nucleic acid interactions.

Sugar-oligoamides have been designed and synthesized as structurally simple carbohydrate-based ligands to study carbohydrate-DNA interactions. The general design of the ligands 1-3 has been done as to favor the bound conformation of Distamycin-type gamma-linked covalent dimers which is a hairpin conformation. Indeed, NMR analysis of the sugar-oligoamides in the free state has indicated the presence of a percentage of a hairpin conformation in aqueous solution. The DNA binding activity of compounds 1-3 was confirmed by calf thymus DNA (ct-DNA) NMR titration. Interestingly, the binding of the different sugar-oligoamides seems to be modulated by the sugar configuration. Semiquantitative structural information about the DNA ligand complexes has been derived from NMR data. A competition experiment with Netropsin suggested that the sugar-oligoamide 3 bind to DNA in the minor groove. The NMR titrations of 1-3 with poly(dA-dT) and poly(dG-dC) suggested preferential binding to the ATAT sequence. TR-NOE NMR experiments for the sugar-oligoamide 3-ct-DNA complex both in D(2)O and H(2)O have confirmed the complex formation and given information on the conformation of the ligand in the bound state. The data confirmed that the sugar-oligoamide ligand is a hairpin in the bound state. Even more relevant to our goal, structural information on the conformation around the N-glycosidic linkage has been accessed. Thus, the sugar asymmetric centers pointing to the NH-amide and N-methyl rims of the molecule have been characterized.

2004

N-acyl substituted 7-amino-4-chloroisocoumarin: a peptide degradation model via an imide mechanism.

During the coupling reaction between 3-alkoxy-7-amino-4-chloroisocoumarin and N-acyl alanine dipeptide, an unexpected deamidation reaction was observed. The proposed mechanism for this reaction involved the formation of an imide intermediate which after cleavage led to the release of amino acid moiety. The described deamidation reaction represents the first chemical model involving a non-peptidic moiety, which mimics biological and chemical deamidation processes occurring in proteins or peptides incorporating an asparagine or a glutamine residue.

2003

New antiviral nucleoside prodrugs await application.

In this review, we intend to highlight outstanding concepts of antiviral nucleoside prodrugs which have been developed in recent years, so as to improve the efficacy of a given antiviral drug or to overcome some drug deficiencies. Examples of antiviral carrier-linked nucleoside prodrugs or nucleoside bioprecursors are described, and their active mechanisms discussed. The described nucleoside prodrugs are classified in two structural classes: prodrugs bearing molecular modifications on the sugar moiety and prodrugs bearing molecular modifications on the nucleic base. Despite the important research work accomplished through out the world during the last few years in developing improved antiviral drugs for the treatment of HIV (human immunodeficiency virus), HBV (hepatitis B virus), HCV (hepatitis C virus), HSV (herpes simplex virus), HCMV (human cytomegalovirus), etc infections, only few nucleoside antiviral prodrugs are marketed, while promising prodrugs deriving from original concepts were developed. The most relevant concepts are discussed: (1) - pronucleotide approach allows the design of prodrugs, which by-pass the first kinase phosphorylation step; (2) - drug design based on Bodor's concept for brain delivery improved drugs and (3) - 5'-O-carbonate nucleosides and deaminase approaches, which allow active drug regeneration. Nonetheless, none of these innovative models have reached the market.

Sans date

HDI Corpus: a Dataset for Named Entity Recognition for In-Context Herb-Drug Interactions