Medicinal Plants Research Center, NPPM, Federal University of Piauí, Teresina, PI, Brazil; Laboratory of Organic Geochemistry, LAGO, Federal University of Piauí, Teresina, PI, Brazil.
Medicinal Plants Research Center, NPPM, Federal University of Piauí, Teresina, PI, Brazil; Department of Veterinary Morphophysiology, Federal University of Piauí, Teresina, PI, Brazil.
Toxicol In Vitro. 2020 Mar;63:104750. doi: 10.1016/j.tiv.2019.104750. Epub 2019 Dec 18.
The present study was directed to the in vitro antileishmanial, cytotoxic and immunomodulatory effects of Garcinielliptone FC (GFC) against promastigote and macrophage-internalized amastigote forms of Leishmania amazonensis. GFC showed in vitro cytotoxicity against BALB/c peritoneal macrophages with CC of 74.90 μM. The hemolytic activity against sheep erythrocytes only demonstrated a decrease of 20.42% in cell viability at the highest tested concentration tested (1326.0 μM). GFC promoted in vitro growth inhibition of both promastigote and intracellular amastigotes with IC values of 14.06 and 1.91 μM, respectively, with 7.3-fold higher Selectivity Index (SI) for intracellular amastigotes (SI = 39.21) than for promastigotes (SI = 5.33). Interestingly, the pre-treatment of macrophages or promastigotes with GFC promoted decrease of infected macrophages and number of recovered amastigotes, respectively. Also, GFC was able to markedly promote macrophages activation by increase of phagocytic capability and nitrite production at concentrations able to solve infection of macrophages by L. amazonensis, suggesting the possible involvement of immunomodulatory modulation of macrophages leading to solve the infection. GFC is an emerging and promising chemical compound for the studies focused on the assessment of its therapeutic potential on in vivo experimental models of leishmaniasis.
本研究旨在研究 Garcinielliptone FC（GFC）对美洲利什曼原虫前鞭毛体和巨噬细胞内化的无鞭毛体形式的体外抗利什曼原虫、细胞毒性和免疫调节作用。GFC 对 BALB/c 腹腔巨噬细胞表现出体外细胞毒性，CC 为 74.90 μM。对绵羊红细胞的溶血活性仅在最高测试浓度（1326.0 μM）下显示细胞活力下降 20.42%。GFC 分别对前鞭毛体和细胞内无鞭毛体的体外生长抑制作用具有 IC 值为 14.06 和 1.91 μM，细胞内无鞭毛体的选择性指数（SI）为 39.21 倍，明显高于前鞭毛体（SI = 5.33）。有趣的是，GFC 预处理巨噬细胞或前鞭毛体可分别降低感染巨噬细胞的数量和恢复的无鞭毛体数量。此外，GFC 能够通过增加吞噬能力和亚硝酸盐的产生来显著促进巨噬细胞的激活，在能够解决巨噬细胞感染美洲利什曼原虫的浓度下，表明可能涉及对巨噬细胞的免疫调节作用，从而解决感染。GFC 是一种新兴的有前途的化学化合物，用于研究其在体内实验性利什曼病模型中的治疗潜力。
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