Antileishmanial polyphenols from Garcinia vieillardii

Seven xanthones, the new vieillardiixanthones B and C (1) and (7), pancixanthones A (2), B (3), 1,6-dihydroxyxanthone (6), pyranojacareubin and 5,6-O-dimethyl-2-deprenylrheediaxanthone together with two benzophenones, clusiachromene (4) and 3-geranyl-2,4,6-trihydroxybenzophenone (5) were isolated from the stem bark of the neocaledonian Garcinia vieillardii. 2, 5 and 6 showed a significant antileishmanial activity against the promastigote forms of Leishmania mexicana and L. infantum and against the amastigote forms of L. infantum

Preparative Isolation, Fast Centrifugal Partition Chromatography Purification and Biological Activity of Cajaflavanone from Derris ferruginea Stems

Introduction The Derris genus is known to contain flavonoid derivatives, including prenylated flavanones and isoflavonoids such as rotenoids, which are generally associated with significant biological activity. Objective To develop an efficient preparative isolation procedure for bioactive cajaflavanone. Methodology Fast centrifugal partition chromatography (FCPC) was optimised to purify cajaflavanone from Derris ferruginea stems in a single step as compared to fractionation from the cyclohexane extract by successive conventional solid–liquid chromatography procedures. The purification yield, purity, time and solvent consumption per procedure are described. The anti-fungal, anti-bacterial, anti-leishmanial, anti-plasmodial, anti-oxidant activities and the inhibition of advanced glycation end-products (AGEs) by cajaflavanone accumulation are described. Results FCPC enabled cajaflavanone purification in a single separation step, yielding sufficient quantities to perform in vitro biological screening. Interestingly, cajaflavanone had an inhibitory effect on the formation of AGEs, without displaying any in vitro anti-oxidant activity. Conclusion A simple and efficient procedure, in comparison with other preparative methods, for bioactive cajaflavone purification has been developed using FCPC

Anti-AGEs and antiparasitic activity of an original prenylated isoflavonoid and flavanones isolated from Derris ferruginea

A new isoflavonoid, 5-hydroxy-3-(4-hydroxyphenyl)-8-isopropenyl-8,9-dihydro-4H-furo-[2,3-h]-chromen-4-one named derrisisoflavone G (1), four known prenylated flavanones (2–5), four known isoflavonoids (6–9) and two phenolic derivatives (10, 11) have been isolated from crude extracts of Derris ferruginea stems and leaves. Compounds 1–11 were identified using spectroscopic methods whereas an unambiguous structural assignment of 1 was accomplished through hemi-synthesis. Compounds 2–5 exhibited strong in vitro antiparasitic activity against Plasmodium falciparum and Leishmania major but with poor selectivity, whereas 1–5 significantly inhibited the formation of advanced glycation endproducts (AGEs)

Recombinant forms of Leishmania amazonensis excreted/secreted promastigote surface antigen (PSA) induce protective immune responses in dogs

International audiencePreventive vaccination is a highly promising strategy for interrupting leishmaniasis transmission that can, additionally, contribute to elimination. A vaccine formulation based on naturally excreted secreted (ES) antigens was prepared from L. infantum promastigote culture supernatant. This vaccine achieved successful results in Phase III trials and was licensed and marketed as CaniLeish. We recently showed that newly identified ES promastigote surface antigen (PSA), from both viable promastigotes and axenically-grown amastigotes, represented the major constituent and the highly immunogenic antigen of L. infantum and L. amazonensis ES products. We report here that three immunizations with either the recombi-nant ES LaPSA-38S (rPSA) or its carboxy terminal part LaPSA-12S (Cter-rPSA), combined with QA-21 as adjuvant, confer high levels of protection in naive L. infantum-infected Beagle dogs, as checked by bone marrow parasite absence in respectively 78.8% and 80% of vaccinated dogs at 6 months post-challenge. The parasite burden in infected vaccinated dogs was significantly reduced compared to placebo group, as measured by q-PCR. Moreover, our results reveal humoral and cellular immune response clear-cut differences between vaccinated and control dogs. An early increase in specific IgG2 antibodies was observed in rPSA/QA-21-and Cter-rPSA/QA-21-immunized dogs only. They were found functionally active in vitro and were highly correlated with vaccine protection. In vaccinated protected dogs, IFN-γ and NO productions, as well as anti-leishmanial macrophage activity, were increased. These data strongly suggest that ES PSA or its carboxy-terminal part, in recom-binant forms, induce protection in a canine model of zoonotic visceral leishmaniasis by inducing a Th1-dominant immune response and an appropriate specific antibody response. These data suggest that they could be considered as important active components in vaccine candidates

Granzyme B-induced mitochondrial ROS are required for apoptosis

Caspases and the cytotoxic lymphocyte protease granzyme B (GB) induce reactive oxygen species (ROS) formation, loss of transmembrane potential and mitochondrial outer membrane permeabilization (MOMP). Whether ROS are required for GB-mediated apoptosis and how GB induces ROS is unclear. Here, we found that GB induces cell death in an ROS-dependent manner, independently of caspases and MOMP. GB triggers ROS increase in target cell by directly attacking the mitochondria to cleave NDUFV1, NDUFS1 and NDUFS2 subunits of the NADH: ubiquinone oxidoreductase complex I inside mitochondria. This leads to mitocentric ROS production, loss of complex I and III activity, disorganization of the respiratory chain, impaired mitochondrial respiration and loss of the mitochondrial cristae junctions. Furthermore, we have also found that GB-induced mitocentric ROS are necessary for optimal apoptogenic factor release, rapid DNA fragmentation and lysosomal rupture. Interestingly, scavenging the ROS delays and reduces many of the features of GB-induced death. Consequently, GB-induced ROS significantly promote apoptosis

Amino acid substitutions in the Candida albicans sterol 5,6-desaturase (Erg3p) confer azole resistance: characterization of two novel mutants with impaired virulence

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