ABSTRACT
The parasites of the genus Leishmania cause a range of leishmaniasis diseases, whose treatment is impaired due to intramacrophage parasites living in the mammalian host. Immunostimulation has been considered an important strategy to leishmaniasis treatment. The immunomodulatory effects of the polysaccharides arabinogalactan (ARAGAL), galactomannan (GMPOLY), and xyloglucan (XGJ), as well as their oxovanadium (IV/V) complexes (ARAGAL:VO, GMPOLY:VO, and XGJ:VO) were evaluated on peritoneal macrophages. At 25 µg/mL of GMPOLY:VO and of XGJ:VO, and 10 µg/mL of ARAGAL:VO, nitric oxide (NO) production by the macrophages was not altered compared with the control group. All polymers increased the production of interleukins 1 beta and 6 (IL-1ß and IL-6), but the oxovanadium complexes were more potent activators of these mediators. ARAGAL:VO 10 µg/mL, GMPOLY:VO and XGJ:VO 25 µg/mL led to an increase of 562%, 1054%, and 523% for IL-1ß, respectively. For IL-6 at the same concentration, the levels increased by 539% and 794% for ARAGAL:VO and GMPOLY:VO, respectively. Polysaccharides and their oxovanadium complexes exhibited important leishmanicidal effects on amastigotes of Leishmania (L.) amazonensis. The native and complexed polymers reduced the growth of promastigote-form Leishmania by â¼60%. This effect was reached at concentrations 12 times lower than that observed for Glucantime (300 µg/mL promoted an inhibition of â¼60%). The 50% inhibitory concentration (IC50) values for the complexes were determined. XGJ:VO showed the lowest IC50 value (6.2 µg/mL; 0.07 µg/mL of vanadium), which for ARAGAL:VO was 6.5 µg/mL (0.21 µg/mL of vanadium) and 7.3 µg/mL (0.06 µg/mL of vanadium) for GMPOLY:VO. The upregulation of IL-1ß and IL-6 release and downregulation of NO production by macrophages and the important leishmanicidal effect are essential to stablish their potential use against this pathology.
Subject(s)
Antiprotozoal Agents/pharmacology , Leishmania/drug effects , Leishmaniasis/drug therapy , Organometallic Compounds/pharmacology , Polysaccharides/pharmacology , Vanadates/pharmacology , Antiprotozoal Agents/chemical synthesis , Antiprotozoal Agents/chemistry , Dose-Response Relationship, Drug , Macrophages/drug effects , Macrophages/metabolism , Molecular Structure , Organometallic Compounds/chemical synthesis , Organometallic Compounds/chemistry , Parasitic Sensitivity Tests , Polysaccharides/chemistry , Structure-Activity Relationship , Vanadates/chemistryABSTRACT
Compounds that activate macrophage antimicrobial activity are potential targets for treatment of leishmaniasis. The present study investigated the in vitro immunomodulatory effects of a galactomannan (GALMAN-A) isolated from seeds of Mimosa scabrella and its oxovanadium (IV/V) complex (GALMAN-A:VO(2+)/VO(3+)) on macrophage activity. GALMAN-A increased nitric oxide levels by ~33% at a concentration of 250µg/ml, while GALMAN-A:VO(2+)/VO(3+) decreased nitric oxide levels by ~33% at a concentration of 50µg/ml. Furthermore, GALMAN-A increased interleukin-1 beta (IL-1ß) and interleukin-6 (IL-6) levels by 5.5 and 2.3 times, respectively, at a concentration of 25µg/ml; at the same concentration, GALMAN-A:VO(2+)/VO(3+) promoted an increase in IL-1ß and IL-6 production by 8 and 5.5 times, respectively. However, neither GALMAN-A nor GALMAN-A:VO(2+)/VO(3+) affected tumor necrosis factor alpha (TNF-α) or interleukin-10 (IL-10) levels. Importantly, both GALMAN-A and GALMAN-A:VO(2+)/VO(3+) exhibited leishmanicidal activity on amastigotes of Leishmania (L.) amazonensis, reaching ~60% activity at concentrations of 100 and 25µg/ml, respectively. These results indicate that GALMAN-A is three times more potent and its oxovanadium complex is twelve times more potent than Glucantime (300µg/ml), which is the drug of choice in leishmaniasis treatment. The IC50 value for GALMAN-A:VO(2+)/VO(3+) was 74.4µg/ml (0.58µg/ml of vanadium). Thus, the significant activation of macrophages and the noted leishmanicidal effect demonstrate the need for further studies to clarify the mechanisms of action of these compounds.
Subject(s)
Coordination Complexes , Leishmania/drug effects , Macrophage Activation/drug effects , Mannans/chemistry , Mannans/pharmacology , Vanadium , Animals , Antiparasitic Agents/chemistry , Antiparasitic Agents/pharmacology , Cells, Cultured , Coordination Complexes/chemistry , Coordination Complexes/pharmacology , Galactose/analogs & derivatives , Interleukin-1beta/metabolism , Interleukin-6/metabolism , Mice , Models, Molecular , Vanadium/chemistry , Vanadium/pharmacologyABSTRACT
The effects of polysaccharides, including xyloglucan from Hymenaea courbaril (XG), galactomannans from Schizolobium parahybae (GMSP) and Mimosa scabrella (GMMS), xanthan gum (XT), sodium hyaluronate (HNa) and Fucogel(®) (FG), on the rheological behavior of cosmetic emulsions were evaluated. These incorporations gave rise to six emulsified systems, denoted XGE, GMSPE, GMMSE, XTE, HNaE and FGE, respectively. The emulsion consistency was found to follow the trend GMSPE>XGE>HNaE>FGE>XTE>GMMSE. In general, the addition of polysaccharides increased the viscoelastic properties of the emulsions and decreased the creep compliance. The neutral polysaccharides (GMSPE, GMMSE) led to better stability of the emulsions after storing for 20 days relative to charged polymers. It was found that polysaccharides XG, GMSP and GMMS, which come from the seeds of native Brazilian plant species, might be used to modify the flow properties and stabilities of oil-water emulsions.
