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Protective effect of alkaloids from Piper longum in rat dopaminergic
neuron injury of 6-OHDA-induced Parkinson′s disease
ZHENG Li1， WANG Hao2， BA Yin-ying1， LIU Hao-long1， WANG Meng1， GUO Wei-wei1， WU Xia1*， YANG Hui2
（1. School of Traditional Chinese Medicine， Capital Medical University， Beijing 100069， China；
2. Beijing Institute of Neural Science， Capital Medical University， Beijing 100069， China）
[Abstract] Objective： To discuss the protective effect of alkaloids from Piper longum（PLA） in rat dopaminergic neuron injury of 6-OHDA-induced Parkinson′s disease and its possible mechanism. Method： The rat PD model was established by injecting 6-OHDA into the unilateral striatum with a brain solid positioner. The PD rats were divided into the PLA group （50 mg·kg-1·d-1）， the madorpa group （50 mg·kg-1·d-1） and the model group， with 15 rats in each group. All of the rats were orally given drugs once a day for 6 weeks. Meanwhile， other 15 rats were randomly selected as the sham operation group， and only injected with normal saline in the unilateral striatum. The behavioral changes were observed with the apomorphine （APO）-induced rotation and rotary rod tests. The number of tyrosine hydroxylase （TH）-positive cells in rat substantia nigra and the density of TH-positive fibers in striatum were detected by tyrosine hydroxylase immunohistochemistry. The content of superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px）， glutathione （GSH）， catalase （CAT）， malondialdehyde （MDA）， nitric oxide （NO） and nitric oxide synthase （NOS） in rat substantia nigra and striatum were measured by the spectrophotometric method. Result： After being induced by APO， PD rats showed obvious rotation behaviors， with decreased time stay on rotary rod and significant reduction in the number of TH-positive cells in sustantia nigra and the density of TH-positive fibers in striatum. The activities of SOD， GSH-Px， CAT， the content of GSH and the total antioxidant capacity significantly decreased， whereas the activities of NOS and the content of MDA， NO significantly increased. PLA could significantly improve the behavioral abnormality of PD rats and increase the number of TH-positive cells in sustantia nigra and the density of TH-positive fibers in striatum. It could up-regulate the activities of SOD， GSH-Px， CAT， the content of GSH and the total antioxidant capacity， and decrease the content of NOS and the content of MDA， NO. Conclusion： Alkaloids from P. longum shows the protective effect in substantia nigra cells of 6-OHDA-induced PD model rats. Its mechanism may be related with their antioxidant activity.
[Key words] Parkinson′s disease； Piper longum； alkaloid； 6-hydroxydopamine； antioxidant
doi：10.4268/cjcmm20140923