He Huan, Guo Wei-Wei, Xu Rong-Rong, Chen Xiao-Qing, Zhang Nan, Wu Xia, Wang Xiao-Min
Beijing Key Lab of TCM Collateral Disease Theory Research and School of Traditional Chinese Medicine, Capital Medical University, 10 Xitoutiao, Youanmen, Beijing, 100069, China.
Beijing Institute for Brain Disorders and Key laboratory of Neurodegenerative Diseases of the Ministry of Education, Capital Medical University, 10 Xitoutiao, Youanmen, Beijing, 10069, China.
BMC Complement Altern Med. 2016 Oct 24;16(1):412. doi: 10.1186/s12906-016-1392-6.
Alkaloids from Piper longum (PLA), extracted from P. longum, have potent anti-inflammatory effects. The aim of this study was to investigate whether PLA could protect dopaminergic neurons against inflammation-mediated damage by inhibiting microglial activation using a lipopolysaccharide (LPS)-induced dopaminergic neuronal damage rat model.
The animal behaviors of rotational behavior, rotarod test and open-field test were investigated. The survival ratio of dopaminergic neurons and microglial activation were examined. The dopamine (DA) and its metabolite were detected by high performance liquid chromatography (HPLC). The effects of PLA on the expression of interleukin (IL)-6, interleukin (IL)-1β and tumor necrosis factor (TNF)-α were detected by enzyme-linked immunosorbent assay (ELISA). Reactive oxygen species (ROS) and nitric oxide (NO) were also estimated.
We showed that the survival ratio of tyrosine hydroxylase-immunoreactive (TH-ir) neurons in the substantia nigra pars compacta (SNpc) and DA content in the striatum were reduced after a single intranigral dose of LPS (10 μg) treatment. The survival rate of TH-ir neurons in the SNpc and DA levels in the striatum were significantly improved after treatment with PLA for 6 weeks. The over-activated microglial cells were suppressed by PLA treatment. We also observed that the levels of inflammatory cytokines, including TNF-α, IL-6 and IL-1β were decreased and the excessive production of ROS and NO were abolished after PLA treatment. Therefore, the behavioral dysfunctions induced by LPS were improved after PLA treatment.
This study suggests that PLA plays a significant role in protecting dopaminergic neurons against inflammatory reaction induced damage.
从荜茇中提取的荜茇生物碱（PLA）具有强大的抗炎作用。本研究旨在使用脂多糖（LPS）诱导的多巴胺能神经元损伤大鼠模型，研究PLA是否能通过抑制小胶质细胞激活来保护多巴胺能神经元免受炎症介导的损伤。
研究了旋转行为、转棒试验和旷场试验等动物行为。检测了多巴胺能神经元的存活率和小胶质细胞的激活情况。通过高效液相色谱（HPLC）检测多巴胺（DA）及其代谢产物。采用酶联免疫吸附测定（ELISA）检测PLA对白细胞介素（IL）-6、白细胞介素（IL）-1β和肿瘤坏死因子（TNF）-α表达的影响。还评估了活性氧（ROS）和一氧化氮（NO）。
我们发现，单次黑质内注射LPS（10μg）处理后，黑质致密部（SNpc）中酪氨酸羟化酶免疫反应性（TH-ir）神经元的存活率和纹状体中的DA含量降低。PLA治疗6周后，SNpc中TH-ir神经元的存活率和纹状体中的DA水平显著提高。PLA治疗可抑制过度激活的小胶质细胞。我们还观察到，PLA治疗后，包括TNF-α、IL-6和IL-1β在内的炎性细胞因子水平降低，ROS和NO的过量产生被消除。因此，PLA治疗后LPS诱导的行为功能障碍得到改善。
本研究表明，PLA在保护多巴胺能神经元免受炎症反应诱导的损伤中起重要作用。
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