Ethyl acetate extract and its major constituent, isorhamnetin 3-O-rutinoside, from Nitraria retusa leaves, promote apoptosis of human myelogenous erythroleukaemia cells.

OBJECTIVE: Fractionation of ethyl acetate extract (EA) obtained from Nitraria retusa leaves was assessed using different methods of chromatography, and isorhamnetin3-O-rutinoside (I3-O-R) was isolated from this extract. Its structure was determined using data obtained from (1) H and (13) C NMR spectra, as well as by various correlation experiments (COSY, HMQC and HMBC). Both EA extract and I3-O-R were investigated for their ability to induce apoptosis in human chronic myelogenous erythroleukaemia cells (K562). MATERIALS AND METHODS: Apoptosis of cells from the K562 line was detected by DNA fragmentation, PARP cleavage and by evaluating activities of caspases 3 and 8. RESULTS: Apoptosis, revealed by DNA fragmentation and PARP cleavage, was observed after 48-h incubation of these human myelogenous erythroleukaemia cells (K562), with the tested products. Likewise, caspase 3 and caspase 8 activities were induced in the presence of the EA extract and I3-O-R after 48 h of incubation. CONCLUSION: Our results strongly suggest the involvement of the extrinsic pathway of apoptosis in cells treated by both the original EA extract and its major component, I3-O-R.

[Efflux pumps: their role in Staphylococcus aureus antibiotic resistance]. / 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.

New dihydrophenanthrene and phenyldihydroisocoumarin constituents of Trema orientalis.

In the course of the chemical investigation of extracts of the trunk bark and root bark of Trema orientalis, three new compounds were isolated, namely, (9S*,10S*)-3-[7-(3,10-dihydroxy-9-hydroxymethyl-2,5-dimethoxy)-9,10-dihydrophenanthrenyl]propenal (1), (9S*,10S*)-3-[7-(5-O-beta-glucopyranosyl-10-hydroxy-9-hydroxymethyl-2,6-dimethoxy)-9,10-dihydrophenanthrenyl]propenal (2), and (3R*,3aR*,4R*,5S*)-6-O-alpha-arabinopyranosyl-8-hydroxy-3-(4-hydroxyphenyl)-4-(4-hydroxyphenyl)-5-(3,5-dihydroxyphenyl)-3,3a-dihydrocyclopenta[1,2,3-de]isobenzopyran-1-one (3, orientoside A). The structures of 1-3 were determined by spectral methods.

Prenylated xanthones as potential P-glycoprotein modulators.

Dimethylallyl (DMA) derivatives of a naturally occurring xanthone (decussatin 1) were prepared. Their activity as potential P-glycoprotein inhibitors was monitored by affinity of direct binding and compared to that of corresponding DMA-flavones. Both classes of compounds exhibited the same structure-activity relationships. Decreasing polarity enhanced the binding affinity for the P-glycoprotein C-terminal cytosolic domain since DMA derivatives were more active, but unsubstituted hydroxyl group close to the carbonyl was required for efficient activity.