Departament of Natural Products, Pharmaceutical Technology Institute, Far-Manguinhos, Fiocruz, Sizenando Nabuco 100 St, Manguinhos, Rio de Janeiro 21041-250, RJ, Brazil.
Health Sciences Center, Natural Produts Research Institut (IPPN), Federal University of Rio de Janeiro, Block H-1° Floor, Rio de Janeiro 21941-590, RJ, Brazil.
Molecules. 2022 Feb 9;27(4):1151. doi: 10.3390/molecules27041151.
The species are a recognized botanical source of a broad structural diversity of lignans and its derivatives. For the first time, Kunth is presented as a promising natural source of the bioactive (-)-grandisin. Phytochemical analyses of extracts from its leaves, branches and inflorescences showed the presence of the target compound in large amounts, with leaf extracts found to contain up to 52.78% in its composition. A new HPLC-DAD-UV method was developed and validated to be selective for the identification of (-)-grandisin being sensitive, linear, precise, exact, robust and with a recovery above 90%. The absolute configuration of the molecule was determined by X-ray diffraction. Despite the identification of several enantiomers in plant extracts, the major isolated substance was characterized to be the (-)-grandisin enantiomer. In vascular reactivity tests, it was shown that the grandisin purified from botanical extracts presented an endothelium-dependent vasorelaxant effect with an IC of 9.8 ± 1.22 μM and around 80% relaxation at 30 μM. These results suggest that has the potential to serve as a renewable source of grandisin on a large scale and the potential to serve as template for development of new drugs for vascular diseases with emphasis on disorders related to endothelial disfunction.
该种植物是木脂素及其衍生物广泛结构多样性的公认植物来源。首次发现，Kunth 是生物活性（-）-大告灵的有前途的天然来源。对其叶、枝和花序提取物的植物化学分析表明，大量存在目标化合物，叶提取物中含量高达 52.78%。开发并验证了一种新的 HPLC-DAD-UV 方法，该方法对（-）-大告灵的鉴定具有选择性，灵敏度高、线性、精确、准确、稳健，回收率高于 90%。通过 X 射线衍射确定了分子的绝对构型。尽管在植物提取物中鉴定出了几种对映异构体，但主要分离出的物质被表征为（-）-大告灵对映异构体。在血管反应性测试中，从植物提取物中分离出的大告灵表现出内皮依赖性血管舒张作用，IC 为 9.8 ± 1.22 μM，在 30 μM 时舒张约 80%。这些结果表明，Kunth 有可能大规模作为大告灵的可再生来源，并且有可能作为开发新血管疾病药物的模板，重点是与内皮功能障碍相关的疾病。
