马缨丹和罗望子提取物及马缨丹中的 Lantadene A 对盘尾丝虫和罗阿丝虫的杀幼虫作用。

Filaricidal properties of Lantana camara and Tamarindus indica extracts, and Lantadene A from L. camara against Onchocerca ochengi and Loa loa.

机构信息

Department of Biochemistry and Molecular Biology, Faculty of Science, University of Buea, Buea, Cameroon.

Institute of Medical Research and Medicinal Plants Studies (IMPM), Yaounde, Cameroon.

出版信息

PLoS Negl Trop Dis. 2018 Jun 13;12(6):e0006565. doi: 10.1371/journal.pntd.0006565. eCollection 2018 Jun.

Abstract

BACKGROUND

Ivermectin is the only drug currently recommended for the treatment of onchocerciasis, the second leading infectious cause of blindness in the world. This drug kills only the first stage larvae-microfilariae (mf) of Onchocerca volvulus and is to be used cautiously in areas where Loa loa is prevalent because of severe adverse events observed with coinfected patients.

METHODOLOGY/PRINCIPAL FINDINGS: This study investigated the anti-filarial activities of two Cameroonian medicinal plants, Lantana camara and Tamarindus indica locally used to treat onchocerciasis. Twelve (12) extracts were prepared and tested in vitro on the bovine model parasite, O. ochengi as well as L. loa mf. Both mf and adult male worm viabilities were assessed by motility scoring, while adult female worm viability was determined biochemically by standard MTT/formazan colorimetry. Cytotoxicity and acute toxicity were determined respectively, in monkey kidney epithelial cells and in BALB/c mice. Pure compounds were isolated by LC/MS using a bio-assay guided strategy. All the extracts showed 100% activity at 500 μg/mL against O. ochengi adult worms and mf. The highest activity against O. ochengi was observed with the hexane extract of L. camara leaves (LCLhex), with IC50 of 35.1 μg/mL for adult females and 3.8 μg/mL for the mf. Interestingly, this extract was more active against O. ochengi mf than L. loa mf. Further studies on the extracts led to the isolation of lantadene A from the methylene chloride extract of L. camara leaves, with IC50s of 7.85 μg/mL for adult males, 10.38 μg/mL for adult females, 10.84 μg/mL for O. ochengi mf and 20.13 μg/mL for L. loa mf.

CONCLUSIONS/SIGNIFICANCE: We report for the first time the anti-onchocercal activities of these locally consumed medicinal plants and lantadene A, a potential lead for further development as an onchocerciasis cure.

摘要

背景

伊维菌素是目前唯一被推荐用于治疗盘尾丝虫病(世界第二大致盲性传染病)的药物。这种药物只能杀死旋盘尾丝虫的第一期幼虫——微丝蚴(mf),并且在流行罗阿罗阿丝虫的地区使用时需要谨慎,因为合并感染的患者会出现严重的不良反应。

方法/主要发现:本研究调查了两种喀麦隆药用植物——马缨丹和罗望子的抗丝虫活性,这些植物在当地用于治疗盘尾丝虫病。共制备了 12 种提取物,并在体外牛模型寄生虫——奥氏曼森线虫以及罗阿罗阿丝虫 mf 上进行了测试。通过运动评分评估 mf 和成虫雄性虫活力,而通过标准 MTT/甲臜比色法测定成虫雌性虫活力。分别在猴肾上皮细胞和 BALB/c 小鼠中测定细胞毒性和急性毒性。使用基于生物测定的策略通过 LC/MS 分离纯化合物。所有提取物在 500μg/mL 时对奥氏曼森线虫成虫和 mf 均显示 100%的活性。对奥氏曼森线虫的最高活性观察到马缨丹叶的正己烷提取物(LCLhex),其对成虫雌性的 IC50 为 35.1μg/mL,对 mf 的 IC50 为 3.8μg/mL。有趣的是,该提取物对奥氏曼森线虫 mf 的活性高于罗阿罗阿丝虫 mf。对提取物的进一步研究导致从马缨丹叶的二氯甲烷提取物中分离出拉坦丁 A,其对成虫雄性的 IC50 为 7.85μg/mL,对成虫雌性的 IC50 为 10.38μg/mL,对奥氏曼森线虫 mf 的 IC50 为 10.84μg/mL,对罗阿罗阿丝虫 mf 的 IC50 为 20.13μg/mL。

结论/意义:我们首次报道了这些当地食用药用植物以及拉坦丁 A 的抗盘尾丝虫活性,拉坦丁 A 可能成为进一步开发盘尾丝虫病治疗方法的潜在先导化合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f01/6016949/a795aa3a917d/pntd.0006565.g001.jpg

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