Stępnik Katarzyna, Kukula-Koch Wirginia, Plazinski Wojciech, Rybicka Magda, Gawel Kinga
Department of Physical Chemistry, Institute of Chemical Sciences, Faculty of Chemistry, Maria Curie-Sklodowska University in Lublin, Pl. M. Curie-Skłodowskiej 3, 20-031 Lublin, Poland.
Department of Pharmacognosy with Medicinal Plants Garden, Medical University of Lublin, ul. Chodzki 1, 20-093 Lublin, Poland.
Pharmaceuticals (Basel). 2023 Aug 31;16(9):1234. doi: 10.3390/ph16091234.
Oleanolic acid (OA), as a ubiquitous compound in the plant kingdom, is studied for both its neuroprotective and neurotoxic properties. The mechanism of acetylcholinesterase (AChE) inhibitory potential of OA is investigated using molecular dynamic simulations (MD) and docking as well as biomimetic tests. Moreover, the in vitro SH-SY5Y human neuroblastoma cells and the in vivo zebrafish model were used. The inhibitory potential towards the AChE enzyme is examined using the TLC-bioautography assay (the IC value is 9.22 μM). The CH-π interactions between the central fragment of the ligand molecule and the aromatic cluster created by the His440, Phe288, Phe290, Phe330, Phe331, Tyr121, Tyr334, Trp84, and Trp279 side chains are observed. The results of the in vitro tests using the SH-SY5Y cells indicate that the viability rate is reduced to 71.5%, 61%, and 43% at the concentrations of 100 µg/mL, 300 µg/mL, and 1000 µg/mL, respectively, after 48 h of incubation, whereas cytotoxicity against the tested cell line with the IC value is 714.32 ± 32.40 µg/mL. The in vivo tests on the zebrafish prove that there is no difference between the control and experimental groups regarding the mortality rate and morphology ( > 0.05).
齐墩果酸（OA）作为植物界中普遍存在的一种化合物，因其神经保护和神经毒性特性而受到研究。采用分子动力学模拟（MD）、对接以及仿生试验等方法，研究了齐墩果酸抑制乙酰胆碱酯酶（AChE）的潜在机制。此外，还使用了体外SH-SY5Y人神经母细胞瘤细胞和体内斑马鱼模型。采用薄层色谱-生物自显影法检测其对AChE酶的抑制潜力（IC值为9.22 μM）。观察到配体分子的中心片段与由His440、Phe288、Phe290、Phe330、Phe331、Tyr121、Tyr334、Trp84和Trp279侧链形成的芳香簇之间的CH-π相互作用。使用SH-SY5Y细胞进行的体外试验结果表明，孵育48小时后，在100 μg/mL、300 μg/mL和1000 μg/mL浓度下，存活率分别降至71.5%、61%和43%，而对受试细胞系的细胞毒性IC值为714.32±32.40 μg/mL。对斑马鱼进行的体内试验证明，对照组和实验组在死亡率和形态方面没有差异（>0.05）。
