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薇甘菊叶凝集素:体外抗利什曼原虫活性及对利什曼原虫内阿米巴形式的免疫调节作用。

Microgramma vacciniifolia Frond Lectin: In Vitro Anti-leishmanial Activity and Immunomodulatory Effects Against Internalized Amastigote Forms of Leishmania amazonensis.

机构信息

Departamento de Bioquímica, Centro de Biociências, Universidade Federal de Pernambuco, Recife, Pernambuco, Brazil.

Núcleo de Pesquisas em Plantas Medicinais-NPPM, Universidade Federal do Piauí, Teresina, Piauí, Brazil.

出版信息

Acta Parasitol. 2023 Dec;68(4):869-879. doi: 10.1007/s11686-023-00717-7. Epub 2023 Oct 24.

Abstract

PURPOSE

The treatment of leishmaniasis, an anthropozoonosis caused by Leishmania protozoa, is limited by factors, such as adverse effects, toxicity, and excessive cost, which has highlighted the importance of novel drugs. In this context, natural products have been considered as sources of antileishmanial agents. This study investigated the leishmanicidal activity of Microgramma vacciniifolia frond lectin (MvFL) on promastigotes and amastigotes of Leishmania amazonensis.

METHODS

The effects of MvFL on promastigote proliferation and macrophage infection by amastigotes were evaluated and mean inhibitory concentrations (IC) were calculated. As a safety assessment, the hemolytic capacity of MvFL (6.25-200 µg/mL) against mouse and human erythrocytes was determined. Additionally, the ability of MvFL (6.25-100 µg/mL) to modulate lysosomal and phagocytic activities and the nitric oxide (NO) production by murine peritoneal macrophages was also investigated.

RESULTS

After 24 h, MvFL inhibited the proliferation of L. amazonensis promastigotes, with an IC of 88 µg/mL; however, hemolytic activity was not observed. MvFL also reduced macrophage infection by amastigotes with an IC of 52 µg/mL. Furthermore, treatment with MvFL reduced the number of amastigotes internalized by infected murine peritoneal macrophages by up to 68.9% within 48 h. At a concentration of 25 µg/mL, MvFL stimulated lysosomal activity of macrophages within 72 h, but did not alter phagocytic activity or induce NO production at any of the tested concentrations.

CONCLUSION

MvFL exerts antileishmanial activity and further studies are needed to assess its therapeutic potential in in vivo experimental models of leishmaniasis.

摘要

目的

利什曼原虫引起的人兽共患疾病——利什曼病的治疗受到副作用、毒性和费用过高的限制,这凸显了新型药物的重要性。在这种情况下,天然产物已被视为抗利什曼药物的来源。本研究调查了 Microgramma vacciniifolia frond lectin(MvFL)对 Leishmania amazonensis 前鞭毛体和无鞭毛体的杀利什曼原虫活性。

方法

评估 MvFL 对前鞭毛体增殖和巨噬细胞感染无鞭毛体的影响,并计算平均抑制浓度(IC)。作为安全性评估,测定 MvFL(6.25-200μg/mL)对小鼠和人红细胞的溶血能力。此外,还研究了 MvFL(6.25-100μg/mL)调节溶酶体和吞噬活性以及诱导鼠腹腔巨噬细胞产生一氧化氮(NO)的能力。

结果

24 小时后,MvFL 抑制 L. amazonensis 前鞭毛体的增殖,IC 为 88μg/mL;但未观察到溶血活性。MvFL 还降低了巨噬细胞感染无鞭毛体的能力,IC 为 52μg/mL。此外,用 MvFL 处理可使感染的鼠腹腔巨噬细胞内的无鞭毛体数量减少多达 68.9%,在 48 小时内。在 25μg/mL 浓度下,MvFL 在 72 小时内刺激巨噬细胞的溶酶体活性,但在任何测试浓度下均不改变吞噬活性或诱导 NO 产生。

结论

MvFL 具有抗利什曼原虫活性,需要进一步研究其在利什曼病体内实验模型中的治疗潜力。

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