Semi-synthesis of new antimicrobial esters from the natural oleanolic and maslinic acids.

In this article, we report an effective procedure for the selective isolation of oleanolic acid 1 and maslinic acid 2 (3.4 and 8.5mg/g DW, respectively) from pomace olive (Olea europaea L.) using an ultrasonic bath, and the synthesis of a series of new triterpenic acid esters. The compounds were characterized by their spectral data and were evaluated for their antimicrobial activity. Among the compounds tested, those having sulfur and chlorine atoms were found to be antibacterial. They showed activity against two Gram-positive bacteria Staphylococcus aureus and Enterococcus faecalis and two Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa (MICs within a range of 5-25µg/mL). The fungus Penicillium italicum was found to be the most sensitive to both sulfur derivatives: (3ß)-3-((thiophene-2-carbonyl)oxy)-olean-12-en-28-oic acid (1a) (IZ=22mm) and (2α,3ß-2,3-bis((thiophene-2-carbonyl)oxy)olean-12-en-28-oic acid (2a) (IZ=24mm).

New septanoside and 20-hydroxyecdysone septanoside derivative from Atriplex portulacoides roots with preliminary biological activities.

The phytochemical investigation of a Tunisian plant Atriplex portulacoides (Chenopodiaceae) led to the isolation of two new compounds designated as portulasoid (2) and septanoecdysone (3) along with the known 20-hydroxyecdysone (20HE) (1). Their chemical structures were elucidated on the basis of extensive spectroscopic methods including ES-HRMS, 1D and 2D-NMR. The isolated compounds were finally tested for their antioxidant activity by using DPPH, ABTS(+), Fe(3+) and catalase assays and also for their antibacterial and anticholinesterase activities.

New antioxidant bibenzyl derivative and isoflavonoid from the Tunisian Salsola tetrandra Folsk.

Two new phytochemical compounds, Tetranins A and B, 1-(3,5'-dihydroxy-4'-méthoxyphenyl)-2-phenylethanol 1 and 5,2'-dihydroxy-5'-methoxy-6,7-methylenedioxy-isoflavone 2, were isolated from the EtOAc extract of Salsola tetrandra roots. They exhibited a significant antioxidant effect in 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical and 2,2'-azinobis (3-ethylbenzothiazoline-6-sulphonic acid (ABTS) assays. Their structures were elucidated by extensive spectroscopic methods including 1-D-((1)H and (13)C) and 2-D-NMR experiments (CHcorr, HMBC, (1)H-(1)H COSY and NOESY) as well as high-resolution ES-MS and they were found to be quite active as antioxidants in the DPPH and ABTS assays.

VEGF and mRNA VEGF expression in CSF from Behçet's disease with neurological involvement.

Vascular endothelial growth factor (VEGF) stimulates angiogenesis, but is also pro-inflammatory and plays an important role in the development of neurological disease, where it can have both attenuating and exacerbating effects. Several studies have indicated that VEGF-A (VEGF) may play a role in the pathogenesis of neurological inflammatory diseases. To assess the role of VEGF in patients with Behçet's disease with neurological involvement, VEGF was measured in the cerebrospinal fluid (CSF) of 32 patients compared to a group of 12 patients with noninflammatory neurological diseases (NIND) and 14 patients with multiple sclerosis (MS). We have also studied the expression of mRNA-VEGF (VEGF-A) in CSF and in peripheral blood mononuclear cells. The mean VEGF(CSF) was significantly increased in neuro-BD and MS patients compared to NIND patients. There was an association between neuro-BD-VEGF(CSF), and leukocyte count. A significant correlation was also observed between neuro-BD-VEGF(CSF) and CSF(%CD4) cells. As a measure of the integrity of the blood-brain barrier Q(albumin) was found correlated to VEGF(CSF). VEGF mRNA was significantly increased in neuro-BD patients compared to NIND patients. These results indicate that, VEGF may be associated with the increased percentages of CD4 cell subpopulation. The role of VEGF is within the inflammatory cascade in the mediation of blood-brain barrier disruption and not specific to Behçet's.

Discrepancies of NKT cells expression in peripheral blood and in cerebrospinal fluid from Behçet's disease.

The precise role of natural killer T (NKT) cells in the pathogenesis of Behçet's disease (BD) remains unknown. The frequency, cytokine profile and heterogeneity of NKT cells were studied in peripheral blood mononuclear cells (PBMC) from 42BD patients and in cerebrospinal fluid (CSF) samples from 9 neuro-BD patients. Flow cytometry revealed a decreased frequency of NKT cells in PBMC from BD patients (median: 0.06%; range: 0%-0.3%) when compared to healthy controls (median: 0.23%; range: 0.1%-0.7%; P<0.01). NKT cells were biased toward a Th(1)-like phenotype, with a significant decrease of IL-4/IFN-gamma ratio in BD (median: 0.049; range: 0.01-0.13) vs. healthy controls (median: 0.82; range: 0.4-1.33; P<0.01). NKT cells were increased in CSF-BD samples (median: 0.18%; range: 0.1%-0.4%), when compared to CSF-NIND patients (median: 0.05%; range: 0.01%-0.09%; P<0.01). Based on the reactivity of PBMC-derived NKT cells toward alpha-galactosylceramide (alpha-GalCer), 80% of BD patients were non-responsive. At the opposite, the reactivity of NKT cells in CSF from BD patients was not impaired. BD-CSF NKT cells exhibited an increased expression of IFN-gamma-producing cells, demonstrating that CSF-NKT cells were functional, and biased toward a Th(1)-like phenotype. These data suggest that functional NKT cells are recruited into BD inflammatory sites contributing to BD pathogenesis.

Cytokine profile in Behçet's disease patients. Relationship with disease activity.

OBJECTIVE: To analyse proinflammatory Th1 and Th2 cytokines in patients with Behçet's disease (BD) in relation to disease activity. METHODS: Forty-five BD patients (25 in active stage) were investigated with ELISA for estimation of cytokines levels. Furthermore, cytokines intracellular synthesis (IL-4 and IFN-gamma) of CD4+ T cells was studied. RESULTS: Active and in remission BD patients showed increased serum levels of Th1 (IFN-gamma, IL-12) and Th2 (IL-4, IL-6 and IL-10) cytokines. Active BD was characterized by a higher increase of IL-6, IL-10 and a striking increase of IL-17, IL-18 and IFN-gamma, compared to remission RD. Upon in vitro stimulation, the percentages of CD4+ T cells containing IFN-gamma and CD40L were higher in active BD compared to healthy controls. CONCLUSION: Our results suggest that the microenvironment of CD4+ T cells in active BD may induce the production of more cells committed to Th1 than in BD patients in remission and healthy controls.