Collaborative Laboratory for Herbal Standardization (CHEST), School of Pharmaceutical Sciences, Universiti Sains Malaysia, George Town 11800, Penang, Malaysia.
Chemical Biology Research Group, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako 351-0198, Saitama, Japan.
Molecules. 2022 Apr 20;27(9):2648. doi: 10.3390/molecules27092648.
(MT) and (SJ) are pharmacologically reported to have anti-oxidant, anti-inflammatory, and anti-diabetic effects, and can be neuroprotective agents. Our previous work revealed that MT and SJ exhibited 76.32% and 93.81% inhibition against acetylcholinesterase (AChE) at 50 μg/mL final concentration in their ethyl acetate and hexane fractions, respectively. This study was aimed to investigate the bioactive constituents of MT and SJ and their molecular mechanism toward AChE inhibition. Bioassay-guided isolation afforded prenylflavonoids - from MT and anacardic acid derivatives and from SJ that were confirmed by NMR and MS data. Compound exerted the strongest anti-AChE potential (IC: 0.54 μM), followed by , , , and (IC: 1.0, 2.4, 6.8, and 33 μM, respectively). In silico molecular docking revealed formed stronger molecular interactions including three H-bonds than its derivative based on the saturation of their alkyl chains. The addition of a five carbon-prenyl chain in increased the number of binding interactions, justifying its greater activity than derivatives and . This research reflects the first report of AChE inhibitors from these species, thereby adding pharmacological values to MT and SJ as potential remedies in neuroprotection.
(MT) 和 (SJ) 在药理学上被报道具有抗氧化、抗炎和抗糖尿病作用，并且可以作为神经保护剂。我们之前的工作表明，在 50μg/mL 的最终浓度下，MT 和 SJ 的乙酸乙酯和正己烷部分分别对乙酰胆碱酯酶 (AChE) 表现出 76.32%和 93.81%的抑制作用。本研究旨在研究 MT 和 SJ 的生物活性成分及其对 AChE 抑制的分子机制。基于生物活性导向的分离，从 MT 中获得了prenylflavonoids - ，从 SJ 中获得了 anacardic 酸衍生物 和 ，这些化合物通过 NMR 和 MS 数据得到了确认。化合物 对 AChE 的抑制作用最强 (IC: 0.54 μM)，其次是 、 、 和 (IC: 1.0、2.4、6.8 和 33 μM)。基于其烷基链的饱和，分子对接显示 形成了比其衍生物 更强的分子相互作用，包括三个氢键。在 中加入一个五碳prenyl 链增加了结合相互作用的数量，这解释了它比衍生物 和 具有更大的活性。这项研究反映了这些物种中 AChE 抑制剂的首次报道，从而为 MT 和 SJ 作为神经保护的潜在治疗方法增加了药理学价值。
