Bi Ying, Qu Peng-Cheng, Wang Qing-Song, Zheng Li, Liu Hao-Long, Luo Rong, Chen Xiao-Qing, Ba Yin-Ying, Wu Xia, Yang Hui
Beijing Key Lab of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University , Beijing , PR China .
Pharm Biol. 2015;53(10):1516-24. doi: 10.3109/13880209.2014.991835. Epub 2015 Apr 10.
Alkaloids of Piper longum L. (Piperaceae) (PLA) include piperine and piperlonguminine. Piper longum and piperine have multiple biological properties including antioxidant activity.
The present study investigated the neuroprotective effects of PLA in a MPTP-induced mouse model of Parkinson's disease.
PLA was prepared by extracting the dry seed of P. longum using 85% ethanol. Adult male C57BL/6 mice were divided into eight groups of 12 rats each. Experimental and control groups received an equivalent volume of saline, 0.5% CMC-Na, and 0.1% Tween 80, treated groups received oral PLA (30, 60, and 120 mg/kg), other groups treated with piperine (60 mg/kg) or Madopar (50 mg/kg). The PLA prevention group (PLA-Pr) administrated PLA (120 mg/kg) for 1 week before MPTP challenged. Except for the PLA-Pr group, others were treated for seven consecutive weeks. Parkinson's disease was induced by injecting MPTP intraperitoneally (25 mg/kg) twice weekly for five consecutive weeks. Dopaminerigic (DA) neurons and their metabolism were detected by UFLC-MS/MS. Tyrosine hydroxylase (TH)-immunohistochemistry assay and Western blotting were performed. The antioxidant enzymatic levels were determined by kit-based assays.
The LD50 value of PLA was determined at 1509 mg/kg of body weight. PLA (60 mg/kg) can significantly increase total movement time and distance (p < 0.05), increase levels of DA (p < 0.05) and DOPAC (p < .05), increase glutathione (GSH) level and superoxide dismutase (SOD) activity (p < 0.05), and decrease the lipid peroxidation of malondiadehycle (MDA) (p < 0.05) in PLA-treated groups as compared with the control group.
Our results indicate that PLA possesses neuroprotective effects and has ameliorative properties in dopaminergic neurons.
长蒌叶胡椒（胡椒科）生物碱（PLA）包括胡椒碱和胡椒龙胍宁。长蒌叶胡椒和胡椒碱具有多种生物学特性，包括抗氧化活性。
本研究调查了PLA在MPTP诱导的帕金森病小鼠模型中的神经保护作用。
通过用85%乙醇提取长蒌叶胡椒的干燥种子制备PLA。成年雄性C57BL/6小鼠分为八组，每组12只。实验组和对照组给予等量的生理盐水、0.5%羧甲基纤维素钠和0.1%吐温80，治疗组给予口服PLA（30、60和120mg/kg），其他组用胡椒碱（60mg/kg）或美多芭（50mg/kg）治疗。PLA预防组（PLA-Pr）在MPTP攻击前1周给予PLA（120mg/kg）。除PLA-Pr组外，其他组连续治疗7周。通过每周两次腹腔注射MPTP（25mg/kg）连续5周诱导帕金森病。通过超高效液相色谱-串联质谱法检测多巴胺能（DA）神经元及其代谢。进行酪氨酸羟化酶（TH）免疫组织化学分析和蛋白质免疫印迹法。通过试剂盒检测法测定抗氧化酶水平。
PLA的半数致死量值确定为1509mg/kg体重。与对照组相比，PLA（60mg/kg）可显著增加总运动时间和距离（p<0.05），增加DA（p<0.05）和3,4-二羟基苯乙酸（DOPAC）水平（p<0.05），增加谷胱甘肽（GSH）水平和超氧化物歧化酶（SOD）活性（p<0.05），并降低丙二醛（MDA）的脂质过氧化（p<0.05）。
我们的结果表明，PLA具有神经保护作用，并对多巴胺能神经元具有改善特性。
