Department of Natural Medicinal Chemistry, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
Bioorg Chem. 2019 Nov;92:103258. doi: 10.1016/j.bioorg.2019.103258. Epub 2019 Sep 5.
Alzheimer disease (AD), a prevalent neurodegenerative disorder, is one of the leading causes of dementia. However, there is no effective drug for this disease to date. Picrasma quassioides (D.Don) Benn, a Chinese traditional medicine, was used mainly for the treatment of inflammation, fever, microbial infection and dysentery. In this paper, we reported that the EtOAc extract of Picrasma quassioides stems showed potential neuroprotective activities in l-glutamate-stimulated PC12 and Aβ-stimulated SH-SY5Y cell models, as well as improved memory and cognitive abilities in AD mice induced by amyloid-β peptide. Moreover, it was revealed that the anti-AD mechanism was related to suppressing neuroinflammatory and reducing Aβ deposition using ELISA assay kits. To clarify the active components of the EtOAc extract of Picrasma quassioides stems, a systematic phytochemistry study led to isolate and identify six β-carboline alkaloids (1-6), seven canthin-6-one alkaloids (7-13), and five quassinoids (14-18). Among them, four β-carbolines (1-3, and 6) and six canthin-6-ones (7-11, and 13) exhibited potential neuroprotective activities in vitro. Based on these date, the structure-activity relationships of alkaloids were discussed. Furthermore, molecular docking experiments showed that compounds 2 and 3 have high affinity for both of dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYPKIA) and butyrylcholinesterase (BuChE).
阿尔茨海默病（AD）是一种常见的神经退行性疾病，是痴呆症的主要原因之一。然而，到目前为止，还没有针对这种疾病的有效药物。苦木科植物算盘子（D.Don）Benn 是一种中药，主要用于治疗炎症、发热、微生物感染和痢疾。在本文中，我们报道了算盘子茎的乙酸乙酯提取物在 l-谷氨酸刺激的 PC12 和 Aβ刺激的 SH-SY5Y 细胞模型中具有潜在的神经保护活性，以及在 Aβ 肽诱导的 AD 小鼠中改善记忆和认知能力。此外，研究结果表明，AD 的抗机制与抑制神经炎症和减少 Aβ 沉积有关，这是通过 ELISA 检测试剂盒得出的。为了阐明算盘子茎的乙酸乙酯提取物的活性成分，进行了系统的植物化学研究，分离并鉴定了六个β-咔啉生物碱（1-6）、七个坎替酮生物碱（7-13）和五个奎宁类化合物（14-18）。其中，四个β-咔啉（1-3 和 6）和六个坎替酮（7-11 和 13）在体外表现出潜在的神经保护活性。基于这些数据，讨论了生物碱的结构-活性关系。此外，分子对接实验表明，化合物 2 和 3 与双特异性酪氨酸磷酸化调节激酶 1A（DYPKIA）和丁酰胆碱酯酶（BuChE）都具有高亲和力。
