Alkaloids from piper longum protect dopaminergic neurons against inflammation-mediated damage induced by intranigral injection of lipopolysaccharide

荜茇中的生物碱可保护多巴胺能神经元免受黑质内注射脂多糖引起的炎症介导的损伤

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作者:Huan He, Wei-Wei Guo, Rong-Rong Xu, Xiao-Qing Chen, Nan Zhang, Xia Wu, Xiao-Min Wang

Background

Alkaloids from Piper longum (PLA), extracted from P. longum, have potent anti-inflammatory effects. The

Conclusion

This study suggests that PLA plays a significant role in protecting dopaminergic neurons against inflammatory reaction induced damage.

Methods

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.

Results

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.

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