Teixeira Maribel, Cerqueira Fátima, Barbosa Carlos Maurício, Nascimento Maria São José, Pinto Madalena
CEQOFFUP--Centro de Estudos de Química Orgânica, Fitoquímica e Farmacologia da Universidade do Porto, Faculdade de Farmácia, Universidade do Porto, R. Aníbal Cunha, 164, 4050-047 Porto, Portugal.
J Drug Target. 2005 Feb;13(2):129-35. doi: 10.1080/10611860400027717.
For the first time the inhibitory effect of xanthone and 3-methoxyxanthone on nitric oxide (NO) production by IFN-gamma/LPS activated J774 macrophage cell line is reported. A remarkable improvement of this effect promoted by encapsulation of these compounds in nanocapsules of poly (DL-lactide-co-glycolide) (PLGA) is also demonstrated. A weak inhibitory effect of 3.6% on NO production by activated macrophages was observed for xanthone at the highest studied concentration (100 microM). This effect was slightly higher for 3-methoxyxanthone at the same concentration, producing a reduction of 16.5% on NO production. In contrast, equivalent concentrations of xanthone and 3-methoxyxanthone incorporated in nanocapsules produced a significant decrease on NO production of 91.8 and 80.0%, respectively. Empty nanocapsules also exhibited a slight NO inhibitory activity, which may be due to the presence of soybean lecithin in the composition of the nanosystems. The viability of the macrophages was not affected either by free or nanoencapsulated xanthones. Fluorescence microscopy analysis confirmed that a phagocytic process was involved in the macrophage uptake of xanthone- and 3-methoxyxanthone-loaded PLGA nanocapsules. Phagocytosis might be the main mechanism responsible for the enhancement of the intracellular delivery of both compounds and consequently for the improvement of their biological effect.
首次报道了呫吨酮和3-甲氧基呫吨酮对IFN-γ/LPS激活的J774巨噬细胞系产生一氧化氮（NO）的抑制作用。还证明了将这些化合物封装在聚（DL-丙交酯-共-乙交酯）（PLGA）纳米胶囊中可显著增强这种作用。在研究的最高浓度（100 microM）下，观察到呫吨酮对活化巨噬细胞产生NO的抑制作用较弱，为3.6%。相同浓度下，3-甲氧基呫吨酮的这种作用略高，使NO产生减少16.5%。相比之下，纳米胶囊中掺入的等量呫吨酮和3-甲氧基呫吨酮分别使NO产生显著降低91.8%和80.0%。空纳米胶囊也表现出轻微的NO抑制活性，这可能是由于纳米系统组成中存在大豆卵磷脂。巨噬细胞的活力不受游离或纳米包封的呫吨酮的影响。荧光显微镜分析证实，吞噬过程参与了巨噬细胞对负载呫吨酮和3-甲氧基呫吨酮的PLGA纳米胶囊的摄取。吞噬作用可能是增强这两种化合物细胞内递送并因此改善其生物学效应的主要机制。
