Instituto de Biotecnología-Instituto de Ciencias Básicas, CONICET, Facultad de Ingeniería, Universidad Nacional de San Juan, Av. Libertador General San Martín 1109 (O), San Juan CP 5400, Argentina.
Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, Chacabuco 915, San Luis 5700, Argentina.
Phytomedicine. 2018 Jan 15;39:66-74. doi: 10.1016/j.phymed.2017.12.020. Epub 2017 Dec 20.
In Argentina, the Amaryllidaceae family (59 species) comprises a wide variety of genera, only a few species have been investigated as a potential source of cholinesterases inhibitors to treat Alzheimer disease (AD).
To study the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of the basic dichloromethane extracts (E) from Hieronymiella aurea, H. caletensis, H. clidanthoides, H. marginata, and H. speciosa species, as well as the isolated compounds from these plant extracts.
AChE and BChE inhibitory activities were evaluated with the Ellman's spectrophotometric method. The alkaloids composition from the E was obtained by gas chromatography-mass spectrometry (GC-MS). The E were successively chromatographed on a silica gel column and permeated on Sephadex LH-20 column to afford the main alkaloids identified by means of spectroscopic data. Additionally, an in silico study was carried out.
Nine known alkaloids were isolated from the E of five Hieronymiella species. Galanthamine was identified in all the species by GC-MS standing out H. caletensis with a relative abundance of 9.79% of the total ion current. Strong AChE (IC = 1.84 - 15.40 µg/ml) and moderate BChE (IC50 = 23.74 - 136.40 µg/ml) inhibitory activities were displayed by the extracts. Among the isolated alkaloids, only sanguinine and chlidanthine (galanthamine-type alkaloids) demonstrated inhibitory activity toward both enzymes. The QTAIM study suggests that sanguinine has the strongest affinity towards AChE, attributed to an additional interaction with Ser200 as well as stronger molecular interactions Glu199 and His440.These results allowed us to differentiate the molecular behavior in the active site among alkaloids possessing different in vitro inhibitory activities.
Hieronymiella species growing in Argentina represent a rich and widespread source of galanthamine and others AChE and BChE inhibitors alkaloids. Additionally, the new trend towards the use of natural extracts as pharmaceuticals rather than pure drugs opens a pathway for the development of a phytomedicine derived from extracts of Hieronymiella spp.
在阿根廷，石蒜科（59 种）包含了各种各样的属，只有少数几种被研究为治疗阿尔茨海默病（AD）的潜在胆碱酯酶抑制剂来源。
研究 Hieronymiella aurea、H. caletensis、H. clidanthoides、H. marginata 和 H. speciosa 物种的基本二氯甲烷提取物（E）以及从这些植物提取物中分离得到的化合物对乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BChE）的抑制活性。
采用 Ellman 的分光光度法评价 AChE 和 BChE 的抑制活性。用气相色谱-质谱联用（GC-MS）获得 E 的生物碱组成。E 依次用硅胶柱色谱和 Sephadex LH-20 柱渗透，通过光谱数据鉴定主要生物碱。此外，还进行了计算机模拟研究。
从 5 种 Hieronymiella 物种的 E 中分离出 9 种已知生物碱。GC-MS 鉴定所有物种中均含有加兰他敏，其中 H. caletensis 的总离子流相对丰度为 9.79%。提取物表现出强烈的 AChE（IC50=1.84-15.40μg/ml）和适度的 BChE（IC50=23.74-136.40μg/ml）抑制活性。在所分离的生物碱中，只有血根碱和石蒜碱（加兰他敏型生物碱）对两种酶均具有抑制活性。QTAIM 研究表明，血根碱与 AChE 具有最强的亲和力，这归因于与 Ser200 以及与 Glu199 和 His440 更强的分子相互作用。这些结果使我们能够区分具有不同体外抑制活性的生物碱在活性部位的分子行为。
在阿根廷生长的 Hieronymiella 物种是加兰他敏和其他 AChE 和 BChE 抑制剂生物碱的丰富而广泛的来源。此外，将天然提取物作为药物而不是纯药物使用的新趋势为开发源自 Hieronymiella spp. 的植物药开辟了一条途径。
