Department of Environmental Biology, University of Rome "La Sapienza", Piazzale Aldo Moro 5, 00185 Rome, Italy.
Department of Chemistry, University of Rome "La Sapienza", Piazzale Aldo Moro 5, 00185 Rome, Italy.
Molecules. 2020 Jul 9;25(14):3140. doi: 10.3390/molecules25143140.
The rationale inspiring the discovery of lead compounds for the treatment of human parasitic protozoan diseases from natural sources is the well-established use of medicinal plants in various systems of traditional medicine. On this basis, we decided to select an overlooked medicinal plant growing in central Italy, Desr. (Lamiaceae), which has been used as a traditional remedy against protozoan diseases, and to investigate its potential against Human African trypanosomiasis (HAT). For this purpose, we assayed three extracts of different polarities obtained from the aerial parts of -namely, water (MarrInc-HO), ethanol (MarrInc-EtOH) and dichloromethane (MarrInc-CHCl)-against (TC221), with the aim to discover lead compounds for the development of antitrypanosomal drugs. Their selectivity index (SI) was determined on mammalian cells (BALB/3T3 mouse fibroblasts) as a counter-screen for toxicity. The preliminary screening selected the MarrInc-CHCl extract as the most promising candidate against HAT, showing an IC value of 28 μg/mL. On this basis, column chromatography coupled with the NMR spectroscopy of a MarrInc-CHCl extract led to the isolation and identification of five compounds i.e. 1-α-linolenoyl-2-palmitoyl-3-stearoyl-- glycerol (), 1-linoleoyl-2-palmitoyl-3-stearoyl--glycerol (), stigmasterol (), palmitic acid (), and salvigenin (). Notably, compounds and were tested on , with the latter being five-fold more active than the MarrInc-CHCl extract (IC = 5.41 ± 0.85 and 28 ± 1.4 μg/mL, respectively). Furthermore, the SI for salvigenin was >18.5, showing a preferential effect on target cells compared with the dichloromethane extract (>3.6). Conversely, stigmasterol was found to be inactive. To complete the work, also the more polar MarrInc-EtOH extract was analyzed, giving evidence for the presence of 2″--allopyranosyl-cosmosiin (), verbascoside (), and samioside (). Our findings shed light on the phytochemistry of this overlooked species and its antiprotozoal potential, providing evidence for the promising role of flavonoids such as salvigenin for the treatment of protozoal diseases.
从天然来源发现治疗人类寄生原生动物疾病的先导化合物的基本原理是药用植物在各种传统医学体系中的广泛应用。基于这一原理，我们决定选择一种在意大利中部被忽视的药用植物 - Desr.（唇形科），该植物已被用作治疗原生动物疾病的传统疗法，并研究其对人类非洲锥虫病（HAT）的潜在作用。为此，我们检测了从该植物的地上部分获得的三种不同极性提取物 - 水（MarrInc-HO）、乙醇（MarrInc-EtOH）和二氯甲烷（MarrInc-CHCl） - 对 （TC221）的活性，旨在发现用于开发抗锥虫药物的先导化合物。它们的选择性指数（SI）在哺乳动物细胞（BALB/3T3 小鼠成纤维细胞）上测定，作为毒性的反筛。初步筛选选择 MarrInc-CHCl 提取物作为最有希望的 HAT 候选物，其 IC 值为 28 μg/mL。在此基础上，MarrInc-CHCl 提取物的柱色谱法结合 NMR 光谱分析导致了五种化合物的分离和鉴定，即 1-α-亚麻酰基-2-棕榈酰基-3-硬脂酰基--甘油（）、1-亚油酰基-2-棕榈酰基-3-硬脂酰基--甘油（）、豆甾醇（）、棕榈酸（）和圣草酚（）。值得注意的是，化合物 和 在 上进行了测试，后者的活性比 MarrInc-CHCl 提取物高五倍（IC = 5.41 ± 0.85 和 28 ± 1.4 μg/mL）。此外，圣草酚的 SI > 18.5，表明与二氯甲烷提取物（>3.6）相比，其对靶细胞具有优先作用。相反，豆甾醇被发现没有活性。为了完成这项工作，还分析了极性更强的 MarrInc-EtOH 提取物，证明存在 2″--allopyranosyl-cosmosiin（）、毛蕊花糖苷（）和山麦冬苷（）。我们的研究结果阐明了这种被忽视物种的植物化学及其抗原生动物的潜力，为黄酮类化合物如圣草酚治疗原生动物疾病的潜在作用提供了证据。
