Effects of Picrasma quassioides and its active constituents on Alzheimer's disease in vitro and in vivo
| Autor: | Jian Xu, Wei Qu, Er-Yan Guo, Yun-Wei Hu, Jie Zhang, Hui-Lin Zhu, Wenyuan Liu, Feng Feng, Ning Xie, Chen Lei, Tao Du |
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| Rok vydání: | 2019 |
| Předmět: |
Phytochemistry
Picrasma quassioides PC12 Cells 01 natural sciences Biochemistry Neuroprotection Mice Structure-Activity Relationship Alzheimer Disease In vivo Cell Line Tumor Drug Discovery medicine Animals Humans Maze Learning Molecular Biology Butyrylcholinesterase Mice Inbred ICR Dose-Response Relationship Drug Molecular Structure biology Traditional medicine Plant Extracts 010405 organic chemistry Chemistry Kinase Organic Chemistry medicine.disease biology.organism_classification In vitro Rats 0104 chemical sciences Disease Models Animal 010404 medicinal & biomolecular chemistry Neuroprotective Agents Picrasma Alzheimer's disease |
| Zdroj: | Bioorganic Chemistry. 92:103258 |
| ISSN: | 0045-2068 |
| DOI: | 10.1016/j.bioorg.2019.103258 |
| Popis: | 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 Aβ25-35-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 Aβ1-42 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). |
| Databáze: | OpenAIRE |
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