Contribution à l’étude de l’huile essentielle de Dipcadi serotinum (l.) Medik du Maroc

Dipcadi serotinum (L.) Medik, est une plante de la famille des Hyacinthaceae, elle est largement utilisée comme réchauffant et aussi pour combattre la jaunisse. Cette plante trouve une large utilisation par la population de la région côtière du Maroc. À notre connaissance l’huile essentielle de cette espèce n’a jamais été étudiée ni chimiquement ni biologiquement. Dans ce contexte, nous avons mené une étude comparative de l’huile essentielle extraite de la partie aérienne et la partie souterraine. Les résultats obtenus pour les rendements et la composition chimique de l’huile essentielle des deux parties étudiés montrent des différences considérables.Mots-clés : Dipcadi serotinum (L.) Medik, huile essentielle, composition chimique, médecine traditionnelle, Maroc.Contribution to the study of the essential oil of Dipcadi serotinum (l.) Medik of MoroccoDipcadi serotinum (L.) Medik, is a plant of the Hyacinthaceae’s family, it is widely used as warming and also to combat the jaundice. This plant is widespread use by the population of the coastal region of Morocco. To our knowledge the essential oil of this species has never been studied or chemically or biologically. In this context, we conducted a comparative study of the essential oil extracted from the aerial part and underground part. The results for yield and chemical composition of essential oil from both sides studied showed significant differences.Keywords : Dipcadi serotinum (L.) Medik, essential oil, chemical composition, traditional medicine, Morocco

Endothelial mineralocorticoid receptor activation enhances endothelial protein C receptor and decreases vascular thrombosis in mice

Previous studies have shown that aldosterone, which activates the mineralocorticoid receptor (MR), promotes thrombosis in animal models. Our objective was to determine whether MR activation/expression in the vascular endothelium could modify thrombotic risk in vivo and to examine thrombin generation at the surface of aortic endothelial cells (HAECs). MR was conditionally overexpressed in vivo in vascular endothelial cells in mice (MR-EC mice) or stimulated with aldosterone in HAECs. Thrombosis after ferric chloride injury was delayed in MR-EC mice compared with controls as well as in wild-type FVB/NRj mice treated with aldosterone (60 mug/kg/d for 21 d). Thrombin generation in platelet-poor plasma did not differ between MR-EC mice and controls. In MR-EC mice, aortic endothelial cell protein C receptor (EPCR) expression was increased. Aldosterone (10(-8) M) attenuated thrombin generation at the surface of cultured HAECs, and this effect was associated with up-regulation of expression of EPCR, which promotes formation of activated protein C. Aldosterone increases EPCR expression via a transcriptional mechanism involving interaction of MR with the specificity protein 1 site. These findings demonstrate that MR activation acts on endothelial cells to protect against thrombosis in physiological conditions and that MR-mediated EPCR overexpression drives this antithrombotic property through enhancing protein C activation

Inactivation of serum response factor contributes to decrease vascular muscular tone and arterial stiffness in mice

RATIONALE: Vascular smooth muscle (SM) cell phenotypic modulation plays an important role in arterial stiffening associated with aging. Serum response factor (SRF) is a major transcription factor regulating SM genes involved in maintenance of the contractile state of vascular SM cells. OBJECTIVE: We investigated whether SRF and its target genes regulate intrinsic SM tone and thereby arterial stiffness. METHODS AND RESULTS: The SRF gene was inactivated SM-specific knockout of SRF (SRF(SMKO)) specifically in vascular SM cells by injection of tamoxifen into adult transgenic mice. Fifteen days later, arterial pressure and carotid thickness were lower in SRF(SMKO) than in control mice. The carotid distensibility/pressure and elastic modulus/wall stress curves showed a greater arterial elasticity in SRF(SMKO) without modification in collagen/elastin ratio. In SRF(SMKO), vasodilation was decreased in aorta and carotid arteries, whereas a decrease in contractile response was found in mesenteric arteries. By contrast, in mice with inducible SRF overexpression, the in vitro contractile response was significantly increased in all arteries. Without endothelium, the contraction was reduced in SRF(SMKO) compared with control aortic rings owing to impairment of the NO pathway. Contractile components (SM-actin and myosin light chain), regulators of the contractile response (myosin light chain kinase, myosin phosphatase target subunit 1, and protein kinase C-potentiated myosin phosphatase inhibitor) and integrins were reduced in SRF(SMKO). CONCLUSIONS: SRF controls vasoconstriction in mesenteric arteries via vascular SM cell phenotypic modulation linked to changes in contractile protein gene expression. SRF-related decreases in vasomotor tone and cell-matrix attachment increase arterial elasticity in large arteries

Design, anticonvulsive and neurotoxic properties of retrobenzamides - N-(nitrophenyl)benzamides and N-(aminophenyl)benzamides

Design, anticonvulsant properties in maximal electroshock-induced seizures [MES] and seizures induced by subcutaneous administration of pentetrazole (scPtz), and neurotoxicity of retrobenzamides (N-(nitrophenyl)benzamides and N-(aminophenyl) benzamides are reported. These data are further compared with those on carbamazepine, phenytoin, ameltolide and other reference compounds. Studies on retrobenzamides in mice dosed intraperitoneally point out a good anticonvulsant potential in the MES test for the amino derivatives (N-(aminophenyl)benzamides) and moderate activity for corresponding "nitro" derivatives. In rats dosed orally, aminoretrobenzamides were, however, less active in the MES test than in mice dosed intraperitoneally. Differences between experimental animal species and administration routes lead to hypothesize rapid metabolization of compounds, reduced intestinal resorption and increased removal from body. The presence of a methyl substitution on the N-phenyl moiety of aminoretrobenzamides attenuated these discrepancies between mice and rats. Present results indicate that pharmacological values - including the dose offering anticonvulsant protection in 50 % of tested animals (ED50) and protective indices - obtained on some retrobenzamides may compete with phenytoin and carbamazepine values. By contrast with phenytoin, some retrobenzamides further exhibit activity in the scPtz test

Anticonvulsant and neurotoxicological properties of 4-amino-N-(2-ethylphenyl)benzamide, a potent ameltolide analogue

A well documented study on the anticonvulsant properties of 4-amino-N-(2-ethylphenyl)benzamide (4-AEPB) is here provided. Initial screening in mice dosed intraperitoneally and rats dosed orally indicated that 4-AEPB is active against maximal electroshock-induced seizures (MES), bur does not protect animals against subcutaneous pentylenetetrazole (sc Ptz)-induced seizures. Quantitative evaluation of anti-MES activity and neurotoxicity of 4-AEPB: given intraperitoneally to mice provided ED50 and TD50 values amounting to 28.6 and 96.3 mu mol/kg respectively, resulting in a protective index (PI = TD50/ED50) equal to 3.36. Further quantitative evaluation in rats dosed orally indicated that the respective ED50 and TD50 values for 4-AEPB were 29.8 and more than 1,530 mu mol/kg, resulting in a very high PI value of over 51. Comparison of anticonvulsant properties and neurotoxicity of 4-AEPB with those previously reported in the literature for two 4-aminobenzamide derivatives, 4-amino-N-(2,6-dimethylphenyl)benzamide (or ameltolide, an antiepileptic drug prototype developed by Eli Lilly), and phenytoin, underlines the value of 4-AEPB for future pharmacological development. In this perspective, an additional favorable element is represented by the ability of 4-AEPB to increase the seizure threshold in the intravenous Ptz seizure threshold test in mice dosed intraperitoneally. Molecular modeling studies show that the translocation of one carbon unit in the isomerization of the 2,6-dimethylphenyl moiety of ameltolide to the 2-ethylphenyl counterpart succeeds in maintaining the conformational low energy presentation adopted by ameltolide, providing clues as to why the 4-AEPB here described is an anticonvulsant agent derived from the 4-aminobenzamide pharmacophore platform as potent as ameltolide

Opioid binding sites in jerboa (Jaculus orientalis) brain: a biochemical comparative study in the awake-active and induced hibernating states.

International audience1. Using tritiated ligands [3H]DADLE, [3H]DAGO, [3H]EKC and [3H]Bremazocine, we have demonstrated the presence of delta, mu and kappa sites in brain membranes from jerboa (Jaculus orientalis), a desert rodent and a true hibernator. 2. A comparative study was realized in the case of the induced hibernating state, indicating a reduction of binding capacities during the hibernation state. 3. Using radioimmunoassay, the endogenous pentapeptide methionine-enkephalin (Met-enk) was evaluated in different areas of jerboa brain in comparison with the effect of induced hibernation on the level of Met-enk. 4. A thermodynamic analysis of the effect of temperature on the binding of opioids, indicates that the hibernating and the active state are energetically different. delta G degrees, delta H degrees and delta S degrees were calculated. A break of the Van't Hoff plot was observed in the active state at 15 degrees C, indicating a possible transition state of membranous phospholipids and/or proteins. 5. The role of phospholipids was studied, using the effect of phospholipase A2 and membrane reconstitution. Phospholipids play a key role in the opioid binding

Conditional inactivation of integrin alpha v subunit in vascular smooth muscle cells decreases thrombin generation in vessels and blood

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