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International audience; Campylobacter is one of the major causes of bacterial gastroenteritis worldwide. Humans are infected by eating contaminated meat and antibacterial activity of essential oils could be one of the solutions to reduce the contamination of animals. Here, we studied the antibacterial activity of the Daucus carota essential oil and its active molecules against Campylobacter and other Gram-negative bacteria. Chemically synthesized molecules including (E)methylisoeugenol, elemicin and eugenol were also studied. The results showed that the entire oil and the (E)-methylisoeugenol which is the more active molecule had a bactericidal effect. 2 Same effects were observed using purified and chemically synthesized molecules. In addition, the intracellular potassium and intracellular ATP contents were affected in Campylobacter cells treated with Daucus carota essential oil and its active molecules. Inhibition of the membrane bound F O F 1-ATPase was also observed. Finally, an efflux mechanism of the Daucus carota essential oil active molecules was described for the first time in gamma proteobacteria and the specific antibacterial activity against Campylobacter jejuni was correlated with the lack of this efflux mechanism in this species.

Many pro-angiogenic factors acting directly or indirectly on the proliferation and differentiation of endothelial cells have been highlighted, in particular: VEGF (‘Vascular Endothelial Growth Factor’), FGF (‘Fibroblast Growth Factor’), PDGF (‘Platelet-Derived Growth Factor’), VEGF exerts its pro-angiogenic activity by binding to the surface of receptors with tyrosine kinase activity (VEGFR). The first objective of this study was to elucidate the composition of the essential oil of the roots of Scolymus grandifloras Desf. The second aim was to describe the intra-species variation in essential oil composition in natural populations of 21 oil samples from different Algerian locations using statistical analysis and bioinformatical study of VEGFR inhibition. The essential oil isolated from the root parts, was a really source of Davanoide compounds. The results of the docking simulation revealed that davanone (Ligand 13) has an affinity to interact with cDNA, VEGF and its receptors. The ADMET properties and BOILED-Egg plot validate the compound 13 pass the brain barrier and have high absorption in the intestines with good bioavailability. The findings of this study contribute to the pharmacological knowledge and the therapeutic efficacy of davanone and can initiate the development of new anti-angiogenic drugs. Results showed that essential oil of Scolymus grandiflorus presented a large level of percentage of davanone, davanol D1 and 2-hydroxy davanone. These components may be a new source of nontoxic anticancer agents. However, an additional in vitro and/or in vivo experimental study should make it possible to verify the theoretical results obtained in silico. Communicated by Ramaswamy H. Sarma

Angiogenes is therefore appears to be a complex phenomenon, finely regulated by various activators (pro-angiogenic factors) and inhibitors (anti-angiogenic factors). Among the pro-angiogenic factors, VEGF (Vascular Endothelial Growth Factor) seems to be one of the main players in tumor angiogenesis. It exerts its pro-angiogenic activity by attaching to the surface of receptors with tyrosine kinase activity (VEGFR). The aim of this research was the bioinformatical study of VEGFR inhibition by essential oils of the Inula viscosa. Analyses of essential oils obtained by hydrodistillation from the aerial parts of the plant were performed using GC and GC/MS analysis. We used molecular modeling approaches as molecular mechanics to theoretical investigation VEGF receptors by natural inhibitors. Nineteen compounds were identified, constituting 90.1-98.8% of the total essential oils. The main components of the plants were (E)-nerolidol (15.5–20.2 %), caryophyllene oxide (10.6–18.1%), (E)-Z-farnesyl acetone (13.2–25.1%) and (E)-β-farnesene (1.5–5.6%). Essential oil samples were clustered into two groups according to their chemical compositions. The molecular dynamics study was conducted for the best inhibitors. A few key residues were identified at the binding site of VEGFR. The Pharmacokinetics was justified by means of lipophilicity and high coefficient of skin permeability. The in silico evaluation of ADME revealed that L19 has high absorption. The essential oil of I. viscosa presents a significant variability. This study revealed that (E)-Z-Farnesylacetone is a functional inhibitor of VEGF activities and subsequently can be the best inhibitors candidate to be scrutinized in vivo and in vitro. Communicated by Ramaswamy H. Sarma

Chemical and genetic diversity of Teucrium polium L. subsp. polium from western Algeria and T. polium L. subsp. capitatum from Corsica were investigated. Diversity within and among the two populations of subspecies was assessed according to the chemical composition of their essential oils and the genetic diversity. Chemical analysis was performed using a combination of capillary GC-RI and GC/MS after fractionation using column chromatography. Genetic structures were mapped using three polymorphic genetic markers: two chloroplast markers (RPL32-TRNL and TRNL-F) and ribosomal nuclear markers (ITS region). The statistical analysis showed that both subspecies were clearly distinguished by these chemical and genetic markers. The oil chemical compositions differed qualitatively and quantitatively between the subspecies. Both collective oils were dominated by hydrocarbon compounds however the Algerian sample oils exhibited higher amounts of hydrocarbon sesquiterpenes than those of Corsica (31.2 g/100 g vs. 4.4 g/100 g) while the latter displayed higher amounts of hydrocarbon monoterpenes than the first (59.3 g/100 g vs. 34.3 g/100 g). Neighbor-joining, Maximum likelihood and Bayesian trees constructed from chloroplast markers and nuclear ITS region sequences showed the existence of two groups associated with taxonomic and chemical characteristics. The study indicated that variation in the essential oil composition within subspecies depends on genetic background. The samples of subsp. capitatum from Corsica are a homogeneous group, in contrast to samples of subsp. polium from Algeria which were clustered in two groups. Chemical and genetic diversity of Algerian populations could be explained by geographical isolation of the populations. In addition, the morphological polymorphism observed throughout the colour of flowers could be explained by environmental parameters as well as the soil pH.

This work is a collection of my teaching activities and postdoctoral researches carried out within the laboratory "Chimie des Produits Naturels" (CPN) and the 'Natural resources' research project supported by the UMR CNRS 6134 "Environmental Sciences" of the University of Corsica Pasquale Paoli. The works concern the characterization of aromatic and medicinal plants (AMP) and products of agriculture through the volatile complex mixtures that are derived. These complex mixtures are essential oils, hydrosols, solvent extracts and volatile fractions. The different steps of the analytical sequence were discussed, the choice of plants and their sampling, the sample preparation, analysis, interpretation of the results using the statistical tool and their enhancement through the research of active molecules. The first part deals with the characterization of the essential oils, hydrosols, solvent extracts and volatile fractions from AMP and the aromas of olive-oils and citrus juices. To do this, we examined the potential of alternative methods to hydrodistillation, such as microwave-assisted extraction and Solid Phase MicroExtraction. The analysis is performed in the laboratory CPN using chromatographic techniques as Gas Chromatography (GC) for quantification and GC coupled with Mass Spectrometry (GC/MS) for the identification of the constituents. We have optimized the analytical sequence using complementary techniques such as column chromatography, SM using chemical ionization mode and the Nuclear Magnetic Resonance for the identification of missing references libraries molecules. The second part concerns the development of a new research axis which aims to highlight the active compounds through the study of antibacterial and antifungal activities of essential oils and plant extracts. We have highlighted the biological properties of essential oils and extracts against bacteria involved in food borne illness and nosocomial infections. The last part is developing the prospects aimed at strengthening the work on the AMP and agricultural products of Corsica by exploring new matrices (polar fraction) and new extraction techniques. The valorization of plant complex mixtures by the search for new antibiotics surpassing the mechanisms of resistance of bacteria and of new antioxidants remains scientific challenge for the future., Ce travail constitue un recueil des mes activités d'enseignement et de recherche postdoctorales réalisées au sein du laboratoire " Chimie des Produits Naturels " (CPN) dans le cadre du projet de recherche " Ressources Naturels " soutenu par l'UMR CNRS 6134 " Sciences de l'Environnement " de l'Université de Corse Pasquale Paoli. Les travaux concernent la caractérisation des Plantes aromatiques et médicinales (PAM) et des produits de l'agroalimentaire au travers des mélanges complexes volatils qui en sont issus. Ces mélanges complexes sont des huiles essentielles, des hydrolats, des extraits aux solvants et des fractions volatiles. Les différentes étapes de la séquence analytique ont été examinées à savoir, le choix des végétaux et leur échantillonnage, la préparation de l'échantillon, son analyse proprement dite, l'interprétation des résultats au moyen de l'outil statistique et leur valorisation au travers de la recherche de principes actifs. La première partie vise à caractériser les huiles essentielles, les hydrolats, les extraits aux solvants et les fractions volatiles issus de PAM et ainsi que les arômes des huiles d'olives et de jus d'agrumes. Pour cela, nous avons examiné les potentialités de méthodes dites alternatives à l'hydrodistillation, méthode conventionnelle pour l'obtention des huiles essentielles et des hydrolats, telles que l'extraction assistée par micro-ondes et la MicroExtraction en Phase Solide. L'analyse proprement est réalisée au laboratoire CPN à l'aide de techniques chromatographiques telles que la Chromatographie en Phase Gazeuse (CPG) pour la quantification et la CPG couplée à la Spectrométrie de Masse (CPG-SM) pour l'identification des constituants des mélanges. Nous avons optimisé la séquence analytique en utilisant la complémentarité des techniques telles que la chromatographie sur colonne, l'utilisation de la SM en mode ionisation chimique et de la Résonance Magnétique Nucléaire pour l'identification de molécules absentes des bibliothèques de références. La deuxième partie concerne le développement d'un axe de recherche nouveau qui vise à mettre en évidence des principes actifs au travers de l'étude des propriétés antibactériennes et antifongiques des huiles essentielles et des extraits de végétaux. Nous avons mis en évidence les propriétés biologiques d'huiles essentielles et d'extraits sur un certain nombre de bactéries impliquées dans des infections nosocomiales et alimentaires. La dernière partie développe les perspectives de travail qui visent à renforcer les travaux sur les PAM et sur les produits identitaires de l'agroalimentaire produits en Corse en explorant de nouvelles matrices d'études (fraction lourde) et de nouvelles techniques d'extraction. La valorisation des mélanges complexes issus des végétaux par la recherche de nouveaux antibiotiques surpassant les mécanismes de résistance des bactéries et de nouveaux antioxydants reste un challenge scientifique d'avenir.

This research project aimed to analyze the anti-trypanosomal and anti-leishmanial potential of essential oils extracted from Vietnamese plants and their constituents. These two important neglected diseases are affecting millions of people either in poorly developed or developing countries despite of many efforts made this past decade to decrease their incidence. Literature data show that some essential oils possessed promising anti-parasitic activity not only in vitro but also in vivo using animal models. 37 Vietnamese essential oils were therefore screened on Trypanosoma brucei brucei bloodstream form and Leishmania mexicana mexicana promastigotes. Their cytotoxicity was also analyzed on two different mammalian cell lines in order to choose the samples showing the best selective effect toward parasites. Among them, 4 essential oils extracted from Litsea cubeba, Curcuma longa, Curcuma zedoaria, and Zingiber officinale revealed selective anti-trypanosomal effect, while the most promising anti-leishmanial one was extracted from Ocimum gratissimum. Their chemical composition was then characterized by gas chromatography coupled with FID and MS detectors. Curlone isolated from Curcuma longa essential oil and curzerene from Curcuma zedoaria one were identified as promising anti-trypanosomal candidates while eugenol was responsible for the selective anti-leishmanial effect of Ocimum gratissimum essential oil. Eugenol was already known for its activity on different Leishmania species. However, its mechanism of action against these parasites remains unknown. As it has been shown that eugenol can interact with ergosterol in Candida albicans membrane, and because ergosterol is also a major sterol in Leishmania plasma membrane, its effect was evaluated on liposomes mimicking Leishmania membrane as well as on Leishmania cells. Our results indicate that eugenol did not induce membrane permeabilization nor membrane fluidization at its IC50, but only at much higher concentrations. We also observed, at this IC50, an inhibition of Leishmania metabolism. Ce projet de recherche a pour but l’étude des potentiels antitrypanosomaux et antileishmaniens d’huiles essentielles extraites de plantes vietnamiennes et leurs constituants. Ces deux maladies négligées touchent des millions de personnes dans des pays peu développés ou en cours de développement et ce, malgré les nombreux efforts consentis durant ces dernières décennies pour réduire leur incidence. Selon les données de la littérature, certaines huiles essentielles présentent une activité antiparasitaire prometteuse, tant in vitro que in vivo sur des modèles animaux. De ce fait, 37 huiles essentielles ont été testées sur la forme sanguine du Trypanosoma brucei brucei et sur les promastigotes Leishmania mexicana mexicana. Par ailleurs, leur cytotoxicité a également été déterminée sur deux lignées cellulaires de mammifères différentes afin de sélectionner les échantillons démontrant un effet sélectif envers les parasites. Parmi ceux-ci, 4 huiles essentielles extraites de Litsea cubeba, Curcuma longa, Curcuma zedoaria, et Zingiber officinale se sont révélées avoir un effet antitrypanosomal sélectif, tandis qu’une huile essentielle extraite de Ocimum gratissimum a présenté l’effet antileishmanien sélectif le plus prometteur. Leur composition chimique a ensuite été caractérisée par chromatographie en phase gazeuse couplée à des détecteurs à spectrométrie de masse et FID. La curlone, isolée à partir de l’huile essentielle de Curcuma longa et le curzerène issu de Curcuma zedoaria ont été identifiés comme des candidats antitrypanosomaux prometteurs alors que l’eugénol s’est révélé être le composant responsable de l’effet antileishmanien sélectif de l’huile essentielle d’ Ocimum gratissimum. Bien que l’eugénol fût déjà connu pour son activité sur plusieurs souches de Leishmania, son mécanisme d’action sur ces parasites reste encore inconnu. Comme il avait été démontré que l’eugénol pourrait interagir avec l’ergostérol dans la membrane Candida albicans et que l’ergostérol est un stérol majeur de la membrane plasmique de Leishmania, son effet a été évalué à la fois sur des liposomes imitant la membrane leishmaniale et sur les cellules de Leishmania elles-mêmes. Nos résultats montrent que l’eugénol n’induit ni une perméabilisation, ni une fluidification de la membrane à sa CI50, mais seulement à de plus hautes concentrations. Par contre, nous avons pu observer une inhibition du métabolisme de Leishmania à cette concentration. (BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 2019