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Bioorg Chem. 2019 Nov;92:103258. doi: 10.1016/j.bioorg.2019.103258. Epub 2019 Sep 5.

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

Author information

1
Department of Natural Medicinal Chemistry, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
2
Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
3
Department of Natural Medicinal Chemistry, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, People's Republic of China; Key Laboratory of Biomedical Functional Materials, China Pharmaceutical University, Nanjing 211198, People's Republic of China.
4
State Key Laboratory of Innovative Natural Medicines and TCM Injections, Jiangxi Qingfeng Pharmaceutical Co., Ltd., Ganzhou 341000, Jiangxi, China.
5
Department of Natural Medicinal Chemistry, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, People's Republic of China; Key Laboratory of Biomedical Functional Materials, China Pharmaceutical University, Nanjing 211198, People's Republic of China; Jiangsu Food & Pharmaceutical Science College, Huaian 223003, People's Republic of China. Electronic address: fengsunlight@163.com.
6
Department of Natural Medicinal Chemistry, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, People's Republic of China. Electronic address: xujian201009@126.com.

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).

KEYWORDS:

Alkaloids; Alzheimer’s disease; Picrasma quassioides

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