Therapeutic effect of a natural squamosamide derivative FLZ on Parkinson's disease model mice induced by LPS plus MPTP.
- Author:
Ling-Hong YU
1
;
Huai-Ling WEI
1
;
Xiu-Qi BAO
1
;
Dan ZHANG
1
;
Hua SUN
1
Author Information
1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
- Publication Type:Journal Article
- MeSH:
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine;
3,4-Dihydroxyphenylacetic Acid;
metabolism;
Acrylamides;
pharmacology;
Animals;
Caffeic Acids;
pharmacology;
Corpus Striatum;
metabolism;
Dopamine;
metabolism;
Homovanillic Acid;
metabolism;
Lipopolysaccharides;
Male;
Mice;
Mice, Inbred C57BL;
Motor Activity;
drug effects;
Neurons;
drug effects;
metabolism;
Parkinson Disease, Secondary;
chemically induced;
metabolism;
pathology;
physiopathology;
Random Allocation;
Tyrosine 3-Monooxygenase;
metabolism
- From:
Acta Pharmaceutica Sinica
2013;48(10):1557-1562
- CountryChina
- Language:Chinese
-
Abstract:
The aim of this study is to investigate the protective effect of N-[2-(4-hydroxyphenyl)ethyl]-2-(2, 5-dimethoxyphenyl)-3-(3-methoxy-4-hydroxyphenyl)acrylamide (FLZ), a novel synthetic squamosamide cyclic derivative, against Parkinson's disease (PD) model mice induced by the inflammatory bacterial endotoxin, lipopolysaccharides (LPS) and the neurotoxin 1-methy-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). C57/BL mice were ip injected LPS (5 mg x kg(-1)) once. One week following the LPS injection, mice received a subcutaneous injection of MPTP (25 mg x kg(-1)) once daily for 2 days. Eight weeks later, FLZ (25, 50 and 75 mg x kg(-1)) was orally administered to mice once daily for 60 days. The motor ability of the mice was evaluated by rod climbing test and footprint test. The dopamine (DA) levels in mouse striatum were determined by high performance liquid chromatography system. The tyrosine hydroxylase (TH)-positive cells were showed by immunohistochemical analysis. FLZ treatment significantly improved motor dysfunction of mice challenged by LPS plus MPTP. The increase of TH-positive cell numbers and elevation of DA levels may be contributed to the beneficial effects of FLZ on motor behavior. This study showed FLZ has significant therapeutic effect on LPS plus MPTP induced chronic PD model, which indicates its potential as a new candidate drug to treat PD.
