Graduate Program in Pharmaceutical Sciences, Federal University of Pará, R. Augusto Corrêa, 01, Guamá, CEP 66075-110 Belém, Pará, Brazil.
Faculty of Pharmacy, Federal University of Ouro Preto, R. Diogo de Vasconcelos, 122, Pilar, CEP 35400-000 Ouro Preto, Minas Gerais, Brazil.
J Ethnopharmacol. 2019 Jan 10;228:99-109. doi: 10.1016/j.jep.2018.09.012. Epub 2018 Sep 7.
Aspidosperma excelsum Benth. (Apocynaceae), a native tree in the Brazilian Amazonia, is traditionally used to treat various diseases, including malaria.
To investigate the chemical constitution, antiplasmodial activity and cytotoxicity of samples obtained from A. excelsum trunk bark by different procedures aiming to evaluate their potential as an antimalarial phytomedicine.
A hydroethanolic extract and alkaloid extracts were prepared and assayed for antiplasmodial activity and cytotoxicity against chloroquine-resistant Plasmodium falciparum (W2 strain) and HepG2 cells, respectively. Taking into account the known occurrence and antimalarial activity of Aspidosperma monoterpene indole alkaloids (MIA), acid-base extractions were carried out and the fractions were assayed for antiplasmodial activity and cytotoxicity. All the samples were analysed by hyphenated chromatographic techniques, such as UPLC-DAD-ESI-MS/MS and HRMS (HPLC-MS MicroTOF), comparing their chemical composition to the literature data.
The hydroethanolic extract disclosed a moderate in vitro activity against chloroquine-resistant Plasmodium falciparum (W2 strain) with IC 23.68 ± 3.08 µg/mL), low cytotoxicity to HepG2 cells (> 250 µg/mL) and good SI (> 10.56). A total of 20 known monoterpene indole alkaloids were identified, seven of which are here firstly described for A. excelsum. Known highly active alkaloids, namely demethylaspidospermine, aspidocarpine, and ochrolifuanine are present in active alkaloid fractions and might contribute to their observed antiplasmodial effect. An alkaloid fraction (Ae-Alk2), obtained directly from trunk bark by extraction with dil. aqueous HCl, pointed out for its activity (IC 8.75±2.26 µg/mL, CC 185.14±1.97 µg/mL, SI 21.16) and should be highlighted as the most promising out of the assayed samples.
The present results represent a preliminary support to the alleged antimalarial use of A. excelsum trunk bark and allowed to highlight alkaloid fractions as promising phytomedicines.
巴西亚马逊地区的本地树种 Aspidosperma excelsum Benth.（夹竹桃科），传统上用于治疗各种疾病，包括疟疾。
通过不同的程序从 Aspidosperma excelsum 的树干皮中获得样品，研究其化学成分、抗疟原虫活性和细胞毒性，以评估其作为抗疟植物药的潜力。
制备水-乙醇提取物和生物碱提取物，并分别测定其对氯喹抗性恶性疟原虫（W2 株）和 HepG2 细胞的抗疟原虫活性和细胞毒性。考虑到 Aspidosperma 单萜吲哚生物碱（MIA）的已知发生和抗疟原虫活性，进行了酸碱提取，并测定了各馏分的抗疟原虫活性和细胞毒性。所有样品均通过 UPLC-DAD-ESI-MS/MS 和 HRMS（HPLC-MS MicroTOF）等联用色谱技术进行分析，将其化学成分与文献数据进行比较。
水-乙醇提取物对氯喹抗性恶性疟原虫（W2 株）具有中等体外活性（IC 23.68 ± 3.08 µg/mL），对 HepG2 细胞的细胞毒性较低（>250 µg/mL），SI 较好（>10.56）。共鉴定出 20 种已知的单萜吲哚生物碱，其中 7 种是首次在 A. excelsum 中描述的。已知高度活性的生物碱，即去甲基阿朴啡、阿朴卡林和奥克洛利福宁存在于活性生物碱馏分中，可能对其观察到的抗疟原虫作用有贡献。直接从树干皮中用稀盐酸提取得到的生物碱馏分（Ae-Alk2）因其活性（IC 8.75±2.26 µg/mL，CC 185.14±1.97 µg/mL，SI 21.16）而引人注目，应该是所测试样品中最有前途的。
本研究结果初步支持了 Aspidosperma excelsum 树干皮的抗疟用途，并突出了生物碱馏分作为有前途的植物药。
