Chair of Food Science, Institute of Nutritional Science, and Interdisciplinary Research Center (IFZ), Justus Liebig University Giessen, Heinrich-Buff-Ring 26-32, 35392 Giessen, Germany; Institute of Pharmaceutical Chemistry, Philipps University Marburg, Marbacher Weg 6-10, 35032 Marburg, Germany; Pharmacognosy Department, Faculty of Pharmacy, Al-Azhar University, 11371 Cairo, Egypt.
Chair of Food Science, Institute of Nutritional Science, and Interdisciplinary Research Center (IFZ), Justus Liebig University Giessen, Heinrich-Buff-Ring 26-32, 35392 Giessen, Germany.
J Chromatogr A. 2020 Jan 4;1609:460438. doi: 10.1016/j.chroma.2019.460438. Epub 2019 Aug 7.
Plants are an important source of natural iridoids. This study demonstrates for the first time the acetylcholinesterase (AChE) inhibitory activity of iridoids belonging to the class of antirrhinosides. As iridoids distinguish the chemical composition of most species of the Plantaginaceae family, the active AChE inhibitors were investigated in the hydro-alcoholic extract of Anarrhinum pubescens Fresen. High-performance thin-layer chromatography (HPTLC) in combination with the AChE inhibition assay is a time and material saving methodology, and thus was employed to directly point to the individual enzyme inhibitors occurring in the plant. The effect-directed screening successfully discovered three active metabolites. These were characterized as antirrhinoside-derived iridoids. Two of these are here reported as newly isolated natural compounds. Identification of the two new metabolites was based on analysis of their collected spectroscopic data (HRMS, 1D and 2D NMR). Their structures were elucidated to be 6-O-, 6'-O-di-trans-cinnamoyl-antirrhinoside (1) and 5-O-, 6-O-difoliamenthoyl-antirrhinoside (3), while the previously known compound 6-O-foliamenthoyl-(6'-O-cinnamoyl)-antirrhinoside (2) was assigned by extensive analysis of its HRMS and HRMS/MS data. The activity of the isolated compounds was referred to the known AChE inhibitor rivastigmine, i.e. their activity were calculated and expressed as values equivalently to rivastigmine. This neuroprotective potential of iridoids mediated through AChE inhibition promote them to compete as natural curatives for neurodegenerative disorders like Alzheimer's disease.
植物是天然吲哚类化合物的重要来源。本研究首次证明了属于抗副糖苷类的吲哚类化合物具有乙酰胆碱酯酶（AChE）抑制活性。由于吲哚类化合物区分了车前科大多数物种的化学成分，因此研究了在 Anarrhinum pubescens Fresen 的水醇提取物中具有活性的 AChE 抑制剂。高效薄层色谱（HPTLC）与 AChE 抑制测定相结合是一种节省时间和材料的方法，因此被用于直接指向植物中发生的个别酶抑制剂。基于定向筛选成功发现了三种活性代谢物。这些被鉴定为抗副糖苷衍生的吲哚类化合物。其中两种是新分离的天然化合物。两种新代谢物的鉴定是基于其收集的光谱数据分析（高分辨率质谱，1D 和 2D NMR）。它们的结构被阐明为 6-O-、6'-O-二反式肉桂酰抗副糖苷（1）和 5-O-、6-O-二佛莱酮基抗副糖苷（3），而先前已知的化合物 6-O-佛莱酮基-（6'-O-肉桂酰基）抗副糖苷（2）是通过对其高分辨率质谱和高分辨率质谱/质谱数据的广泛分析来确定的。分离化合物的活性参考了已知的 AChE 抑制剂 rivastigmine，即通过计算并以 rivastigmine 的等效值表示其活性。通过 AChE 抑制介导的吲哚类化合物的神经保护潜力促使它们作为天然治疗剂与阿尔茨海默病等神经退行性疾病竞争。
