Yu Ling-Hong, Wei Huai-Ling, Bao Xiu-Qi, Zhang Dan, Sun Hua
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.
Yao Xue Xue Bao. 2013 Oct;48(10):1557-62.
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.
本研究旨在探讨新型合成鳞状酰胺环衍生物N-[2-(4-羟基苯基)乙基]-2-(2,5-二甲氧基苯基)-3-(3-甲氧基-4-羟基苯基)丙烯酰胺(FLZ)对炎性细菌内毒素脂多糖(LPS)和神经毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的帕金森病(PD)模型小鼠的保护作用。C57/BL小鼠腹腔注射一次LPS(5mg·kg⁻¹)。LPS注射一周后,小鼠每天皮下注射一次MPTP(25mg·kg⁻¹),共2天。八周后,将FLZ(25、50和75mg·kg⁻¹)口服给予小鼠,每天一次,持续60天。通过爬杆试验和足迹试验评估小鼠的运动能力。用高效液相色谱系统测定小鼠纹状体内的多巴胺(DA)水平。通过免疫组织化学分析显示酪氨酸羟化酶(TH)阳性细胞。FLZ治疗显著改善了LPS加MPTP攻击小鼠的运动功能障碍。TH阳性细胞数量的增加和DA水平的升高可能有助于FLZ对运动行为的有益作用。本研究表明,FLZ对LPS加MPTP诱导的慢性PD模型具有显著的治疗作用,这表明其作为治疗PD的新候选药物的潜力。