lignans and Parasitemia

The (-)-hinokinin display high activity against Trypanosoma cruzi in vitro and in vivo. (-)-Hinokinin-loaded poly(D,L-lactide-co-glycolide) microparticles were prepared and characterized in order to protect (-)-hinokinin of biological interactions and promote its sustained release for treatment of Chagas disease. The microparticles contain (-)-hinokinin were prepared by the classical method of the emulsion/solvent evaporation. The scanning electron microscopy, light-scattering analyzer were used to study the morphology and particle size, respectively. The encapsulation efficiency was determined, drug release studies were kinetically evaluated, and the trypanocidal effect was evaluated in vivo. (-)-Hinokinin-loaded microparticles obtained showed a mean diameter of 0.862 microm with smooth surface and spherical shape. The encapsulation efficiency was 72.46 +/- 2.92% and developed system maintained drug release with Higuchi kinetics. The preparation method showed to be suitable, since the morphological characteristics, encapsulation efficiency, and in vitro release profile were satisfactory. In vivo assays showed significant reduction of mice parasitaemia after administration of (-)-hinokinin-loaded microparticles. Thus, the developed microparticles seem to be a promising system for sustained release of (-)-hinokinin for treatment of Chagas disease.

Topics: 4-Butyrolactone; Animals; Antiprotozoal Agents; Benzodioxoles; Chagas Disease; Delayed-Action Preparations; Dioxanes; Dioxoles; Disease Models, Animal; Humans; Lactic Acid; Lignans; Mice; Microspheres; Parasitemia; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Treatment Outcome; Trypanosoma cruzi

Extracts from Holostylis reniformis were tested in vivo against Plasmodium berghei and in vitro against a chloroquine-resistant strain of Plasmodium falciparum. The hexane extract of the roots was the most active, causing 67% reduction of parasitemia in vivo. From this extract, six lignans, including a new (7'R,8S,8'S)-3',4'-methylenedioxy-4,5-dimethoxy-2,7'-cyclolignan-7-one, were isolated and tested in vitro against P. falciparum. The three most active lignans showed 50% inhibitor concentrations of < or =0.32 microM. An evaluation of minimum lethal dose (30%) values showed low toxicity for these lignans in a hepatic cell line (Hep G2A16). Therefore, these compounds are potential candidates for the development of antimalarial drugs.

Topics: Animals; Antimalarials; Aristolochiaceae; Cell Line, Tumor; Chromatography, High Pressure Liquid; Circular Dichroism; Formazans; Humans; Inhibitory Concentration 50; Lignans; Mice; Molecular Conformation; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Parasitemia; Plant Extracts; Plant Roots; Plasmodium berghei; Plasmodium falciparum; Spectrophotometry, Ultraviolet; Tetralones