Serviço de Fitoquímica e Prospecção Farmacêutica, Divisão de Ciência e Inovação, Fundação Ezequiel Dias, Belo Horizonte, MG, Brazil.
Herbário PAMG, Departamento de Pesquisa, Empresa de Pesquisa Agropecuária de Minas Gerais, Belo Horizonte, MG, Brazil.
J Ethnopharmacol. 2019 Mar 1;231:125-140. doi: 10.1016/j.jep.2018.10.039. Epub 2018 Nov 3.
Species of Aspidosperma are known popularly as "peroba, guatambu, carapanaúba, pau-pereiro" and "quina". The genus can be found in the Americas, mainly between Mexico and Argentina. Many species of Aspidosperma are used by the population in treating cardiovascular diseases, malaria, fever, diabetes and rheumatism. The phytochemical aspects of the species of the genus Aspidosperma have been studied extensively. The monoterpene indole alkaloids are the main secondary metabolites in Aspidosperma species, and about 250 of them have been isolated showing a considerable structural diversity. Several of them have showed some important pharmacological activities. Aspidosperma subincanum Mart. and Aspidosperma tomentosum Mart. (Apocynaceae) are Brazilian species widely used by the population to treat diabetes mellitus, hypercholesterolemia. The pharmacological activities of both species have been investigated and the biological properties described can be related to their isolated indole alkaloids. However, more pharmacological studies are needed in order to justify the use of these species in folk medicine. In this review, we present reports mainly focused on chemical and biological studies and their relationship with the ethnopharmacological use of both Aspidosperma species.
The aim of this review is to present their ethnopharmacological use as correlated to their biological activities as described for the extracts and isolated compounds from Aspidosperma subincanum Mart. and Aspidosperma tomentosum Mart. In addition, some aspects related to the biosynthetic pathways are discussed, also NMR assignments and some synthesis information about indole alkaloids from both Aspidosperma species are included.
The bibliographic search was made in theses and dissertations using some databases such as NDLTD (Networked Digital Library of Theses and Dissertations), OATD (Open Access Theses and Dissertations) and Google Scholar. More data were gathered from books, Brazilian journals and articles available on electronic databases such as, Google Scholar, PubChem, Scifinder, Web of Science, SciELO, PubMed and Science Direct. Additionally, the Google Patents and Espacenet Patent Search (EPO) were also consulted. The keywords Aspidosperma, A. subincanum, A. tomentosum, indole alkaloids were used in the research. The languages were restricted to Portuguese, English and Spanish and references were selected according to their relevance.
A. subincanum Mart. and A. tomentosum Mart. (Apocynaceae) are Brazilian species widely used by the population to treat a few diseases. Extracts and isolated compounds of both species have shown antitumor and antimalarial activities. The antitumor activity of isolated compounds has been extensively studied. However, the antiplasmodial activity needs to be investigated further as well as the anti-inflammatory, anti-hyperlipidemic and anorexigenic activities. From A. subincanum twenty-one indole alkaloids were isolated and some of them have been extensively studied. From the leaves and bark of A. tomentosum four alkaloids and one flavonoid were isolated. Furthermore, CG-MS analysis of seeds, branches, leaves and arils identified nine indole alkaloids. Stemmadenine has been proposed as a precursor of indole alkaloids obtained from some species of Aspidosperma. Many of the biosynthetic steps have been characterized at the enzymatic level and appropriate genes have been identified, however, other steps have yet to be investigated and they are still controversial. Some isolated alkaloids from A. subincanum and A. tomentosum were identified only by mass spectrometry. In many cases, their NMR data was either not available or was incomplete. The described meta-analysis of the available NMR data revealed that the chemical shifts belonging to the indole ring might be used to characterize this class of alkaloids within complex matrices such as plant extracts. The biological activities and the structural complexity of these compounds have stimulated the interest of many groups into their synthesis. In this review, some information about the synthesis of indole alkaloids and their derivatives was presented.
A. subincanum and A. tomentosum are used by the population of Brazil to treat many diseases. A few biological activities described for the extracts and isolated compounds of both species are in agreement with the ethnopharmacological use for others species of Aspidosperma, such as, antimalarial, the treatment of diabetes and other illnesses. These species are sources of leading compounds which can be used for developing new drugs. In addition, other biological activities reported and suggested by ethnopharmacological data have yet to be investigated and could be an interesting area in the search for new bioactive compounds.
属于夹竹桃科的 Aspidosperma 物种通常被称为“peroba、guatambu、carapanaúba、pau-pereiro”和“quina”。该属分布于美洲,主要分布在墨西哥和阿根廷之间。许多 Aspidosperma 物种被人们用于治疗心血管疾病、疟疾、发热、糖尿病和风湿。Aspidosperma 属植物的植物化学方面已经得到了广泛的研究。单萜吲哚生物碱是 Aspidosperma 物种中的主要次生代谢物,约有 250 种已被分离出来,显示出相当大的结构多样性。其中一些具有重要的药理活性。巴西的 Aspidosperma subincanum Mart. 和 Aspidosperma tomentosum Mart.(夹竹桃科)是被广泛用于治疗糖尿病、高胆固醇血症的物种。这两个物种的药理活性已经得到了研究,描述的生物特性可以与其分离的吲哚生物碱相关联。然而,为了证明这些物种在民间医学中的使用是合理的,还需要进行更多的药理学研究。在这篇综述中,我们主要介绍了化学和生物学研究的报告,并将其与 Aspidosperma subincanum Mart. 和 Aspidosperma tomentosum Mart. 的民族药理学用途相关联。此外,还讨论了一些与生物合成途径相关的方面,包括 NMR 分配和这两个 Aspidosperma 物种的吲哚生物碱的一些合成信息。
本综述的目的是介绍它们的民族药理学用途,以及它们的提取物和分离化合物的生物活性,这些活性已被描述为 Aspidosperma subincanum Mart. 和 Aspidosperma tomentosum Mart. 的生物活性。此外,还讨论了一些与生物合成途径相关的方面,包括 NMR 分配和这两个 Aspidosperma 物种的吲哚生物碱的一些合成信息。
使用 NDLTD(论文和学位论文网络数字图书馆)、OATD(开放获取论文和学位论文)和 Google Scholar 等数据库进行文献检索。还从书籍、巴西期刊和可在 Google Scholar、PubChem、Scifinder、Web of Science、SciELO、PubMed 和 Science Direct 等电子数据库中获得更多数据。此外,还查阅了 Google Patents 和 Espacenet Patent Search(EPO)。研究中使用了 Aspidosperma、A.subincanum、A.tomentosum、吲哚生物碱等关键词。语言仅限于葡萄牙语、英语和西班牙语,参考文献根据其相关性进行选择。
巴西的 Aspidosperma subincanum Mart. 和 Aspidosperma tomentosum Mart.(夹竹桃科)是被广泛用于治疗几种疾病的物种。这两个物种的提取物和分离化合物都显示出抗肿瘤和抗疟活性。对分离化合物的抗肿瘤活性进行了广泛的研究。然而,抗疟活性需要进一步研究,以及抗炎、抗高血脂和厌食症活性。从 A.subincanum 中分离出二十一种吲哚生物碱,其中一些已被广泛研究。从 A.tomentosum 的叶子和树皮中分离出四种生物碱和一种类黄酮。此外,通过 CG-MS 分析种子、树枝、叶子和浆果皮鉴定出九种吲哚生物碱。Stemmadenine 被提出作为从某些 Aspidosperma 物种中获得的吲哚生物碱的前体。许多生物合成步骤已经在酶水平上进行了特征描述,并且已经鉴定出适当的基因,但是其他步骤尚未进行研究,仍然存在争议。从 A.subincanum 和 A.tomentosum 中分离出的一些生物碱仅通过质谱鉴定。在许多情况下,它们的 NMR 数据要么不可用,要么不完整。对现有 NMR 数据的元分析表明,吲哚环的化学位移可能用于在植物提取物等复杂基质中表征此类生物碱。这些化合物的生物活性和结构复杂性激发了许多研究小组对其合成的兴趣。在这篇综述中,介绍了一些吲哚生物碱及其衍生物的合成信息。
巴西的 Aspidosperma subincanum Mart. 和 Aspidosperma tomentosum Mart. 被巴西人民用于治疗许多疾病。一些已被描述的提取物和分离化合物的生物活性与其他 Aspidosperma 物种的民族药理学用途一致,例如抗疟、治疗糖尿病和其他疾病。这些物种是开发新药的先导化合物的来源。此外,其他已报道并由民族药理学数据提示的生物活性仍有待研究,这可能是寻找新的生物活性化合物的一个有趣领域。