PDF(Pubmed)
Abstract：
Chagas disease (CD) is a worldwide public health problem, and the drugs available for its treatment have severe limitations. Red propolis is a natural extract known for its high content of phenolic compounds and for having activity against T. cruzi. The aim of this study was to investigate the trypanocidal potential of red propolis to isolate, identify, and indicate the mode of action of the bioactive compounds. The results revealed that the total phenolic content was 15.4 mg GAE/g, and flavonoids were 7.2 mg QE/g. The extract was fractionated through liquid-liquid partitioning, and the trypanocidal potential of the samples was evaluated using the epimastigote forms of the Y strain of T. cruzi. In this process, one compound was characterized by MS, 1H, and 13C NMR and identified as vestitol. Cytotoxicity was evaluated employing MRC-5 fibroblasts and H9C2 cardiomyocytes, showing cytotoxic concentrations above 15.62 μg/mL and 31.25 μg/mL, respectively. In silico analyses were applied, and the data suggested that the substance had a membrane-permeation-enhancing effect, which was confirmed through an in vitro assay. Finally, a molecular docking analysis revealed a higher affinity of vestitol with farnesyl diphosphate synthase (FPPS). The identified isoflavan appears to be a promising lead compound for further development to treat Chagas disease.
摘要：
南美锥虫病(CD)是一个世界性的公共卫生问题,可用于治疗的药物有严重的局限性。红色蜂胶是一种天然提取物，以其高含量的酚类化合物和具有抗克氏杆菌的活性而闻名。这项研究的目的是研究红色蜂胶的锥虫杀虫潜力，identify,并指示生物活性化合物的作用模式。结果表明，总酚含量为15.4mgGAE/g，黄酮类化合物为7.2mgQE/g。提取物通过液-液分配进行分馏，并且使用T.cruzi的Y菌株的epimastigote形式评估样品的杀锥虫潜力。在这个过程中,一种化合物通过MS表征，1H,和13CNMR并鉴定为vestitol。使用MRC-5成纤维细胞和H9C2心肌细胞评估细胞毒性，显示细胞毒性浓度高于15.62μg/mL和31.25μg/mL，分别。应用了计算机模拟分析，数据表明该物质具有增强膜渗透的作用，这是通过体外试验证实的。最后,分子对接分析显示vestitol与法尼基二磷酸合酶（FPPS）的亲和力更高。鉴定的异黄酮似乎是一种有前途的先导化合物，可进一步开发治疗查加斯病。
