The complete genome sequence of the gram-positive bacterium Bacillus subtilis.

Bacillus subtilis is the best-characterized member of the Gram-positive bacteria. Its genome of 4,214,810 base pairs comprises 4,100 protein-coding genes. Of these protein-coding genes, 53% are represented once, while a quarter of the genome corresponds to several gene families that have been greatly expanded by gene duplication, the largest family containing 77 putative ATP-binding transport proteins. In addition, a large proportion of the genetic capacity is devoted to the utilization of a variety of carbon sources, including many plant-derived molecules. The identification of five signal peptidase genes, as well as several genes for components of the secretion apparatus, is important given the capacity of Bacillus strains to secrete large amounts of industrially important enzymes. Many of the genes are involved in the synthesis of secondary metabolites, including antibiotics, that are more typically associated with Streptomyces species. The genome contains at least ten prophages or remnants of prophages, indicating that bacteriophage infection has played an important evolutionary role in horizontal gene transfer, in particular in the propagation of bacterial pathogenesis.

Codeine accumulation and elimination in larvae, pupae, and imago of the blowfly Lucilia sericata and effects on its development.

The aim of this study was to evaluate the reliability of insect larvae as samples for toxicological investigations. For this purpose, larvae of Lucilia sericata were reared on samples of minced pig liver treated with different concentrations of codeine: therapeutic, toxic, and potentially lethal doses. Codeine was detected in all tested larvae, confirming the reliability of these specimens for qualitative toxicology analysis. Furthermore, concentrations measured in larvae were correlated with levels in liver tissue. These observations bring new elements regarding the potential use of opiates concentrations in larvae for estimation of drug levels in human tissues. Morphine and norcodeine, two codeine metabolites, have been also detected at different concentrations depending on the concentration of codeine in pig liver and depending on the substance itself. The effects of codeine on the development of L. sericata were also investigated. Results showed that a 29-h interval bias on the evaluation of the larval stage duration calculated from the larvae weight has to be considered if codeine was present in the larvae substrate. Similarly, a 21-h interval bias on the total duration of development, from egg to imago, has to be considered if codeine was present in the larvae substrate.

Novel use of a whole cell E. coli bioreporter as a urinary exposure biomarker.

Bacterial bioreporters have substantial potential for contaminant assessment but their real world application is currently impaired by a lack of sensitivity. Here, we exploit the bioconcentration of chemicals in the urine of animals to facilitate pollutant detection. The shore crab Carcinus maenas was exposed to the organic contaminant 2-hydroxybiphenyl, and urine was screened using an Escherichia coli-based luciferase gene (luxAB) reporter assay specific to this compound. Bioassay measurements differentiated between the original contaminant and its metabolites, quantifying bioconcentration factors of up to one hundred-fold in crab urine. Our results reveal the substantial potential of using bacterial bioreporter assays in real-time monitoring of biological matricesto determine exposure histories, with wide ranging potential for the in situ measurement of xenobiotics in risk assessments and epidemiology.

Dimethylarginines, homocysteine metabolism, and cerebrospinal fluid markers for Alzheimer's disease.

Dimethylarginine and homocysteine metabolism are closely linked and alterations of both were observed in plasma and cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD). CSF parameters of homocysteine metabolism have recently been found to be associated with the CSF level of the AD biomarker phosphorylated tau (ptau) in AD patients. To investigate possible relationships between homocysteine and dimethylarginine metabolism and the AD CSF biomarkers ptau181 and amyloid-β 1-42 (Aβ42), we assessed parameters of homocysteine metabolism (CSF homocysteine, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), 5-methyltetrahydrofolate (5-MTHF)) and dimethylarginine metabolism (plasma and CSF asymmetric dimethylarginine (ADMA), symmetric dimethylarginine, L-arginine) as well as CSF Aβ42 and ptau181 in 98 controls and 51 AD patients. Multivariate linear regression analyses were performed to assess associations between the considered parameters. SAH concentrations show significant associations to CSF ADMA levels, and CSF ADMA and L-arginine to ptau181, but not to Aβ42 concentrations in AD patients. When including concentrations of homocysteine, 5-MTHF, SAM, and SAH into the analysis, CSF ADMA concentrations independently predicted ptau181 levels in AD patients but homocysteine-related metabolites were associated with ptau181 only when ADMA was removed from the analysis model. These results suggest that CSF ADMA may interact with CNS homocysteine metabolism and may contribute to neurodegeneration and accumulation of phosphorylated tau in AD. Functional and interventional studies are needed to further proof this hypothesis.

Screening for wound-induced oxylipins in Arabidopsis thaliana by differential HPLC-APCI/MS profiling of crude leaf extracts and subsequent characterisation by capillary-scale NMR

A simple non-targeted differential HPLC-APCI/MS approach has been developed in order to survey metabolome modifications that occur in the leaves of Arabidopsis thaliana following wound-induced stress. The wound-induced accumulation of metabolites, particularly oxylipins, was evaluated by HPLC-MS analysis of crude leaf extracts. A generic, rapid and reproducible pressure liquid extraction procedure was developed for the analysis of restricted leaf samples without the need for specific sample preparation. The presence of various oxylipins was determined by head-to-head comparison of the HPLC-MS data, filtered with a component detection algorithm, and automatically compared with the aid of software searching for small differences in similar HPLC-MS profiles. Repeatability was verified in several specimens belonging to different series. Wound-inducible jasmonates were efficiently highlighted by this non-targeted approach without the need for complex sample preparation as is the case for the 'oxylipin signature' procedure based on GC-MS. Furthermore this HPLC-MS screening technique allowed the isolation of induced compounds for further characterisation by capillary-scale NMR (CapNMR) after HPLC scale-up. In this paper, the screening method is described and applied to illustrate its potential for monitoring polar and non-polar stress-induced constituents as well as its use in combination with CapNMR for the structural assignment of wound-induced compounds of interest

Analytical methods for the quantitative determination of selective serotonin reuptake inhibitors for therapeutic drug monitoring purposes in patients.

Five selective serotonin reuptake inhibitors (SSRIs) have been introduced recently: citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline. Although no therapeutic window has been defined for SSRIs, in contrast to tricyclic antidepressants, analytical methods for therapeutic drug monitoring of SSRIs are useful in several instances. SSRIs differ widely in their chemical structure and in their metabolism. The fact that some of them have N-demethylated metabolites, which are also SSRIs, requires that methods be available which allow therapeutic drug monitoring of the parent compounds and of these active metabolites. most procedures are based on prepurification of the SSRIs by liquid-liquid extraction before they are submitted to separation by chromatographic procedures (high-performance liquid chromatography, gas chromatography, thin layer chromatography) and detection by various detectors (UV, fluorescence, electrochemical detector, nitrogen-phosphorus detector, mass spectrometry). This literature review shows that most methods allow quantitative determination of SSRIs in plasma, in the lower ng/ml range, and that they are, therefore, suitable for therapeutic drug monitoring purposes of this category of drugs.

Absorption and pharmacokinetics of grapefruit flavanones in beagles

The present study evaluated the pharmacokinetics of three different grapefruit flavanone forms in dog plasma and demonstrated their absorption after an oral intake of a grapefruit extract; pharmacokinetic parameters of these forms were also determined. Ten healthy beagles were administered 70 mg citrus flavonoids as a grapefruit extract contained in capsules, while two additional dogs were used as controls and given an excipient. The grapefruit flavanone naringin, along with its metabolites naringenin and naringenin glucuronide, was detected in dog plasma. Blood samples were collected between 0 and 24 h after administration of the extract. Naringin reached its maximun plasma concentration at around 80 min, whereas naringenin and naringenin glucuronide reached their maximun plasma concentrations at around 20 and 30 min, respectively. Maximum plasma concentrations of naringin, naringenin and naringenin glucuronide (medians and ranges) were 0·24 (0·05 2·08), 0·021 (0·001 0·3) and 0·09 (0·034 0·12) mmol/l, respectively. The areas under the curves were 23·16 l (14·04 70·62) min £ mmol/for nariningin, 1·78 (0·09 4·95) min £ mmol/l for naringenin and 22·5 (2·74 99·23) min £ mmol/l for naringenin glucuronide. The median and range values for mean residence time were 3·3 (1·5 9·3), 2·8 (0·8 11·2) and 8·0 (2·3 13·1) h for naringin, naringenin and naringenin glucuronide, respectively. The results of the present study demonstrate the absorption of grapefruit flavanones via the presence of their metabolites in plasma, thus making an important contribution to the field since the biological activities ascribed to these compounds rely on their specific forms of absorption.

Absorption and pharmacokinetics of green tea catechins in beagles

The present study evaluates for the first time in dogs, the kinetics of green tea catechins and their metabolic forms in plasma and urine. Ten beagles were administered 173 mg (12·35 mg/kg body weight) of catechins as a green tea extract, in capsules. Blood samples were collected during 24 h after intake and urine samples were collected during the following periods of time: 02, 26, 68 and 824 h. Two catechins with a galloyl moiety and three conjugated metabolites were detected in plasma. Most of the detected forms in plasma reached their maximum plasma concentration (Cmax) at around 1 h. Median Cmax for (2)-epigallocatechin-3-gallate (EGCG), (2)-epicatechin-3-gallate (ECG), (2)-epigallocatechin glucuronide (EGCglucuronide), (2)-epicatechin glucuronide (EC-glucuronide), (2)-epicatechin sulphate (EC sulphate) were 0·3 (range 0·11·9), 0·1 (range 00·4), 0·8 (range 0·23·9), 0·2 (range 0·1 1·7) and 1 (range 0·33·4) mmol/l, respectively. The areas under the plasma concentration v. time curves (AUC0!24) were 427 (range 1021185) mmol/l £ min for EGC-glucuronide, 112 (range 53919) mmol/l £ min for EC-sulphate, 71 (range 26306) mmol/l £ min for EGCG, 40 (range 12258) mmol/l £ min for EC-glucuronide and 14 (range 0·1124) mmol/l £ min for ECG. The values of mean residence time (MRT0!24) were 5 (range 216), 2 (range 111), 10 (range 213), 3 (range 216) and 2·4 (range 118) h for EGCG, ECG, EGC-glucuronide, EC-glucuronide and EC sulphate, respectively. In urine, catechins were present as conjugated forms, suggesting bile excretion of EGCG and ECG. Green tea catechins are absorbed following an oral administration and EGC-glucuronide is the metabolic form that remains in the organism for a longer period of time, suggesting that this compound could suffer an enterohepatic cycle.

Absorption and pharmacokinetics of grapefruit flavanones in beagles

The present study evaluated the pharmacokinetics of three different grapefruit flavanone forms in dog plasma and demonstrated their absorption after an oral intake of a grapefruit extract; pharmacokinetic parameters of these forms were also determined. Ten healthy beagles were administered 70 mg citrus flavonoids as a grapefruit extract contained in capsules, while two additional dogs were used as controls and given an excipient. The grapefruit flavanone naringin, along with its metabolites naringenin and naringenin glucuronide, was detected in dog plasma. Blood samples were collected between 0 and 24 h after administration of the extract. Naringin reached its maximun plasma concentration at around 80 min, whereas naringenin and naringenin glucuronide reached their maximun plasma concentrations at around 20 and 30 min, respectively. Maximum plasma concentrations of naringin, naringenin and naringenin glucuronide (medians and ranges) were 0·24 (0·05 2·08), 0·021 (0·001 0·3) and 0·09 (0·034 0·12) mmol/l, respectively. The areas under the curves were 23·16 l (14·04 70·62) min £ mmol/for nariningin, 1·78 (0·09 4·95) min £ mmol/l for naringenin and 22·5 (2·74 99·23) min £ mmol/l for naringenin glucuronide. The median and range values for mean residence time were 3·3 (1·5 9·3), 2·8 (0·8 11·2) and 8·0 (2·3 13·1) h for naringin, naringenin and naringenin glucuronide, respectively. The results of the present study demonstrate the absorption of grapefruit flavanones via the presence of their metabolites in plasma, thus making an important contribution to the field since the biological activities ascribed to these compounds rely on their specific forms of absorption.

Cultivos intercalares e controle de plantas daninhas em plantios de maracujá-amarelo

Objetivou-se identificar cultivos intercalares e métodos integrados de controle de plantas daninhas em maracujá-amarelo (Passiflora edulis Sims f. flavicarpa Deg.) como fatores que viabilizem a sua produção e rentabilidade. O experimento foi instalado em maio de 1999, conduzido em espaldeira vertical com um fio de arame a 2,0m do solo, no espaçamento de 2,5m x 5,0m, em blocos casualizados, com seis tratamentos e quatro repetições, sendo T1: milho (Zea mays L. - BR 106) como cultura intercalar; T2: feijão (Phaseolus vulgaris L. - cultivar Pérola) como cultura intercalar; T3: feijão-de-porco nas entrelinhas e capina com enxada nas linhas; T4: feijão-de-porco nas entrelinhas e controle químico nas linhas (glifosate a 1,5 kg/ha); T5: planta daninha controlada quimicamente (em toda a parcela com alachlor a 2,8 kg/ha + diuron a 1,2 kg/ha em pré-emergência e glifosate a 1,5 kg/ha em pós-emergência); e T6: testemunha (capina com enxada em área total). Os dados analisados, no período de produção (maio de 1999 a abril de 2000), mostraram que não houve diferenças estatísticas entre os tratamentos para produtividade (indústria), peso médio, comprimento e diâmetro dos frutos, sólidos solúveis totais e acidez. Contudo, houve significância para produtividade total e in natura, com destaque para a utilização do feijão como cultura intercalar, com produtividade do maracujazeiro de 12,82 t/ha. Tanto o milho como o feijão podem ser recomendados como culturas intercalares no primeiro ano de cultivo do maracujá-amarelo. Os herbicidas aplicados em pré e pós-emergência foram economicamente viáveis e não mostraram efeito tóxico sobre as plantas de maracujá-amarelo.

The anticancer drug tamoxifen counteracts the pathology in a mouse model of duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a severe disorder characterized by progressive muscle wasting,respiratory and cardiac impairments, and premature death. No treatment exists so far, and the identification of active substances to fight DMD is urgently needed. We found that tamoxifen, a drug used to treat estrogen-dependent breast cancer, caused remarkable improvements of muscle force and of diaphragm and cardiac structure in the mdx(5Cv) mouse model of DMD. Oral tamoxifen treatment from 3 weeks of age for 15 months at a dose of 10 mg/kg/day stabilized myofiber membranes, normalized whole body force, and increased force production and resistance to repeated contractions of the triceps muscle above normal values. Tamoxifen improved the structure of leg muscles and diminished cardiac fibrosis by~ 50%. Tamoxifen also reduced fibrosis in the diaphragm, while increasing its thickness,myofiber count, and myofiber diameter, thereby augmenting by 72% the amount of contractile tissue available for respiratory function. Tamoxifen conferred a markedly slower phenotype to the muscles.Tamoxifen and its metabolites were present in nanomolar concentrations in plasma and muscles,suggesting signaling through high-affinity targets. Interestingly, the estrogen receptors ERa and ERb were several times more abundant in dystrophic than in normal muscles, and tamoxifen normalized the relative abundance of ERb isoforms. Our findings suggest that tamoxifen might be a useful therapy for DMD.

Neuropeptide Y and corticotropin-releasing hormone in CSF mark response to antidepressive treatment with citalopram.

Neuropeptides appear to play a role in the pathophysiology of depression and electroconvulsive treatment and lithium affect these compounds in human cerebrospinal fluid (CSF) and rodent brain. Consequently, we investigated whether long-term treatment with the selective serotonin reuptake inhibitor (SSRI) citalopram (Cit) would also affect neuropeptides in CSF of depressed patients. Changes in CSF monoamine metabolites were also explored. CSF concentrations of corticotropin-releasing hormone (CRH)-like immunoreactivity (-LI), neuropeptide Y (NPY)-LI, and Cit were determined in 21 patients with major depression. Lumbar puncture was performed in the morning at baseline and was repeated after at least 4 wk of Cit treatment (40 mg/d). The severity of depression was assessed by the Hamilton Rating Scale for Depression (HAMD). Cit treatment was associated with a significant increase in NPY-LI and decrease in CRH-LI. An evaluation of the relationship between changes in concentrations of NPY-LI, CRH-LI, and the clinical response showed significant correlations between these parameters. Significant NPY and CRH changes in CSF following treatment as well as correlations to changes in HAMD support the hypothesis that these two peptides play a role in affective disorders and are markers of therapeutic response.

Arabidopsis Basic Helix-Loop-Helix Transcription Factors MYC2, MYC3, and MYC4 Regulate Glucosinolate Biosynthesis, Insect Performance, and Feeding Behavior.

Arabidopsis thaliana plants fend off insect attack by constitutive and inducible production of toxic metabolites, such as glucosinolates (GSs). A triple mutant lacking MYC2, MYC3, and MYC4, three basic helix-loop-helix transcription factors that are known to additively control jasmonate-related defense responses, was shown to have a highly reduced expression of GS biosynthesis genes. The myc2 myc3 myc4 (myc234) triple mutant was almost completely devoid of GS and was extremely susceptible to the generalist herbivore Spodoptera littoralis. On the contrary, the specialist Pieris brassicae was unaffected by the presence of GS and preferred to feed on wild-type plants. In addition, lack of GS in myc234 drastically modified S. littoralis feeding behavior. Surprisingly, the expression of MYB factors known to regulate GS biosynthesis genes was not altered in myc234, suggesting that MYC2/MYC3/MYC4 are necessary for direct transcriptional activation of GS biosynthesis genes. To support this, chromatin immunoprecipitation analysis showed that MYC2 binds directly to the promoter of several GS biosynthesis genes in vivo. Furthermore, yeast two-hybrid and pull-down experiments indicated that MYC2/MYC3/MYC4 interact directly with GS-related MYBs. This specific MYC-MYB interaction plays a crucial role in the regulation of defense secondary metabolite production and underlines the importance of GS in shaping plant interactions with adapted and nonadapted herbivores.

Etude de la toxicité hépatique de la cocaïne associée à de l'alcool: Effets de l'éthanol sur le métabolisme de la cocaïne dan les hépatocytes de rat en suspension et dans un modèle enzymatique humain

Le but essentiel de notre travail a été d?étudier la capacité du foie, premier organe de métabolisation des xénobiotiques, à dégrader la cocaïne en présence d?éthanol, à l?aide de deux modèles expérimentaux, à savoir un modèle cellulaire (les hépatocytes de rat en suspension) et un modèle acellulaire (modèle reconstitué in vitro à partir d?enzymes purifiées de foie humain). La première partie a pour objectifs de rechercher les voies de métabolisation de la cocaïne qui sont inhibées et / ou stimulées en présence d?éthanol, sur hépatocytes isolés de rat. Dans ce but, une méthode originale permettant de séparer et de quantifier simultanément la cocaïne, le cocaéthylène et huit de leurs métabolites respectifs a été développée par Chromatographie Phase Gazeuse couplée à la Spectrométrie de Masse (CPG / SM). Nos résultats préliminaires indiquent que l?éthanol aux trois concentrations testées (20, 40 et 80 mM) n?a aucun effet sur la cinétique de métabolisation de la cocaïne. Notre étude confirme que l?addition d?éthanol à des cellules hépatiques de rat en suspension supplémentées en cocaïne résulte en la formation précoce de benzoylecgonine et de cocaéthylène. L?apparition retardée d?ecgonine méthyl ester démontre l?activation d?une deuxième voie de détoxification. La production tardive d?ecgonine indique une dégradation de la benzoylecgonine et de l?ecgonine méthyl ester. De plus, la voie d?oxydation intervenant dans l?induction du stress oxydant en produisant de la norcocaïne est tardivement stimulée. Enfin, notre étude montre une métabolisation complète de la concentration initiale en éthanol par les hépatocytes de rat en suspension. La deuxième partie a pour but de déterminer s?il existe d?autres enzymes que les carboxylesterases formes 1 et 2 humaines ayant une capacité à métaboliser la cocaïne seule ou associée à de l?éthanol. Pour ce faire, une méthode de micropurification par chromatographie liquide (Smart System®) a été mise au point. Dans le cadre de nos dosages in situ de la cocaïne, du cocaéthylène, de la benzoylecgonine, de l?acide benzoïque et de la lidocaïne, une technique par Chromatographie Liquide Haute Performance couplée à une Détection par Barrette de Diode (CLHP / DBD) et une méthode de dosage de l?éthanol par Chromatographie Phase Gazeuse couplée à une Détection par Ionisation de Flamme équipée d?un injecteur à espace de tête (espace de tête CPG / DIF) ont été développées. La procédure de purification nous a permis de suspecter la présence d?autres enzymes que les carboxylesterases formes 1 et 2 de foie humain impliquées dans le métabolisme de la cocaïne et déjà isolées. A partir d?un modèle enzymatique reconstitué in vitro, nos résultats préliminaires indiquent que d?autres esterases que les formes 1 et 2 de foie humain sont impliquées dans l?élimination de la cocaïne, produisant benzoylecgonine et ecgonine méthyl ester. De plus, nous avons montré que les sensibilités de ces enzymes à l?éthanol sont variables.<br/><br/>The main purpose of our work was to study the ability of the liver, as the first organ to metabolise xenobiotic substances, to degrade cocaine in the presence of ethanol. In order to do this, we used two experimental models, namely a cellular model (rat liver cells in suspension) and an a-cellular model (model reconstructed in vitro from purified human liver enzymes). The purpose of the first part of our study was to look for cocaine metabolising processes which were inhibited and / or stimulated by the presence of ethanol, in isolated rat liver cells. With this aim in mind, an original method for simultaneously separating and quantifying cocaine, cocaethylene and eight of their respective metabolites was developed by Vapour Phase Chromatography coupled with Mass Spectrometry (VPC / MS). Our preliminary results point out that ethanol at three tested concentrations (20, 40 et 80 mM) have no effect on the kinetic of metabolisation of cocaine. Our study confirms that the addition of alcohol to rat liver cells in suspension, supplemented with cocaine, results in the premature formation of ecgonine benzoyl ester and cocaethylene. The delayed appearance of ecgonine methyl ester shows that a second detoxification process is activated. The delayed production of ecgonine indicates a degradation of the ecgonine benzoyl ester and the ecgonine methyl ester. Moreover, the oxidising process which occurs during the induction of the oxidising stress, producing norcocaine, is stimulated at a late stage. Finally, our study shows the complete metabolisation of the initial alcohol concentration by the rat liver cells in suspension. The second part consisted in determining if enzymes other than human carboxylesterases 1 and 2, able to metabolise cocaine on its own or with alcohol, existed. To do this, a micropurification method us ing liquid phase chromatography (Smart System®) was developed. A technique based on High Performance Liquid Chromatography coupled with a Diode Array Detection (HPLC / DAD) in the in situ proportioning of cocaine, cocaethylene, ecgonine benzoyl ester, benzoic acid and lidocaine, and a method for proportioning alcohol by quantifying the head space using Vapour Phase Chromatography coupled with a Flame Ionisation Detection (head space VPC / FID) were used. The purification procedure pointed to the presence of enzymes other than the human liver carboxylesterases, forms 1 and 2, involved in the metabolism of cocaine and already isolated. The preliminary results drawn from an enzymatic model reconstructed in vitro indicate that human liver carboxylesterases, other than forms 1 and 2, are involved in the elimination of cocaine, producing ecgonine benzoyl ester and ecgonine methyl ester. Moreover, we have shown that the sensitivity of these enzymes to alcohol is variable.

Investigation phytochimique des plantes aquatiques Potamogeton pectinatus L., P. lucens L., P. perfoliatus L. et P. crispus L. (Potamogetonaceae)

Dans le cadre de la recherche de nouveaux composés naturels, les métabolites secondaires de plantes aquatiques indigènes, les potamots Potamogeton pectinatus L., P. lucens L., P. perfoliatus L. et P. crispus L. (Potamogetonaceae), ont été étudiés. Par leur position écologique et évolutive particulière entre environnement terrestre et aquatique, les plantes aquatiques ou macrophytes pourraient en effet avoir sélectionné des composés avec des caractéristiques originales. Les extraits dichlorométhaniques (apolaires) des potamots ont été analysés par HPLCUV, HPLC-MS, HPLC-RMN et GC-MS, et testés contre diverses cibles biologiques. Sur la base de ces résultats, les extraits apolaires de P. pectinatus et P. lucens ont été étudiés de manière plus approfondie. Ils ont été fractionnés sur des colonnes ouvertes et par VLC, LPLC, MPLC, CPC et HPLC semi-préparative. Une partie de leurs constituants ont été isolés et leurs structures déterminées par des méthodes spectroscopiques, en particulier par RMN et par MS. Quinze composés ont été ainsi isolés de P. pectinatus et P. lucens, dont sept sont des nouveaux produits naturels. Parmi ces quinze produits, neuf sont des diterpènes ent-labdanes contenant un noyau furane ou un groupe lactonique, dont six sont décrits ici pour la première fois. Certains de ces diterpènes ont montré une activité algicide, ce qui indique une de leurs fonctions possible dans les potamots, et un de ces labdanes, le méthyl-15,16-époxy-12-oxo-8(17),13(16),14-ent-labatrièn-19-oate, a également des propriétés anti-inflammatoires. Les composés présents dans les extraits méthanoliques (polaires) n?ont pas été isolés, mais quatorze d?entre eux ont pu être identifiés par HPLC-UV, HPLC-MS et HPLCRMN. Une majorité de ces constituants sont des flavonoïdes connus, des dérivés glycosylés de l?apigénine, la lutéoline et le chrysoériol, également présents en tant qu?aglycones. Plusieurs ent-labdanes glycosylés ont pu être également identifiés dans ces extraits, parmi lesquels un nouveau composé dont la structure a pu être partiellement déterminée. En conclusion, ce travail a permis de mieux connaître la phytochimie de plusieurs plantes aquatiques de Suisse, et d?isoler de nouveaux produits naturels avec des propriétés biologiques et pharmacologiques intéressantes.<br/><br/>The secondary metabolites of Swiss freshwater plants, the pondweeds Potamogeton pectinatus L., P. lucens L., P. perfoliatus L. and P. crispus L. (Potamogetonaceae), were investigated. Because of their peculiar habitat, in-between aquatic and terrestrial life, aquatic plants should produce secondary metabolites with original chemical or biological features. Their apolar extracts were analysed by HPLC-UV, HPLC-MS, HPLC-NMR and GCMS, and were tested with different bioassays. Based on these results, the apolar extracts of P. pectinatus and P. lucens were investigated more extensively. They were fractionated on open columns, and by VLC, LPLC, MPLC, CPC and semi-preparative HPLC. Their constituents were isolated and their structures elucidated by spectroscopic methods as MS and NMR. Fifteen compounds could be isolated from P. pectinatus and P. lucens, and seven were new natural products. Nine of them were ent-labdane diterpenes with a furan moiety or a lactone group, and six of these labdanes were reported here for the first time as natural products. Some of these diterpenes showed an algaecide effect. This activity indicated their potential ecological function in pondweeds. One compound, methyl-15,16-epoxy-12-oxo-8(17),13(16),14-ent-labatrien-19-oate, revealed also some anti-inflammatory properties. The constituents of polar extracts were not isolated, but fourteen of them could be identified by HPLC-UV, HPLC-MS and HPLC-NMR. The major part of these compounds was known flavonoids as apigenin, lutolin, chrysoeriol and their glycosylated derivatives. Several glycosylated ent-labdanes were also identified, and the structure of a new labdane dihexoside was partially elucidated. In conclusion this study allowed a better knowledge of the phytochemistry of Swiss aquatic plants, and the isolation of new natural products with interesting biological and pharmacological properties.