Effects of Picrasma quassioides and its active constituents on Alzheimer's disease in vitro and in vivo.

Abstract

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).

• Authors: Eryan Guo, Yunwei Hu, Tao Du, Huilin Zhu, Lei Chen, Wei Qu, Jie Zhang, Ning Xie, Wenyuan Liu, Feng Feng, Jian Xu
• Journal: Bioorganic chemistry (Bioorg Chem) Vol. 92 Pg. 103258 (11 2019) ISSN: 1090-2120 [Electronic] United States
• PMID: 31520892 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Neuroprotective Agents
• Plant Extracts

Topics

• Alzheimer Disease (drug therapy, pathology)
• Animals
• Cell Line, Tumor
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Humans
• Maze Learning (drug effects)
• Mice
• Mice, Inbred ICR
• Molecular Structure
• Neuroprotective Agents (chemistry, isolation & purification, pharmacology)
• PC12 Cells
• Picrasma (chemistry)
• Plant Extracts (chemistry, isolation & purification, pharmacology)
• Rats
• Structure-Activity Relationship