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Objective Inflammatory processes have been implicated as one of the active contributors to dopaminergic neuronal damage in the development and progression of Parkinsons disease (PD).Alkaloids from Piper longum (PLA), extracted from P.longum, have potent anti-uiflammatory effects.The aim of this study was to investigate whether PLA could protect dopaminergic neurons against inflammation-mediated damage by using a lipopolysaccharide (LPS)-induced dopaminergic neuronal damage rat model.METHODS PD rat model was induced by intranigral injection of LPS (10 μg) followed by PLA treatment for 6 weeks.Animal behavior and survival ratio of dopaminergic neurons were investigated.The dopamine (DA) and its metabolite were detected by high performance liquid chromatography (HPLC).Microglial activation was revealed by immunohistochemical staining of ionized calcium binding adaptor molecule-1 (Iba-1).Inflammatory cytokines such as interleukin (IL)-6, interleukin (IL)-1β and tumour necrosis factor (TNF)-α were detected by enzyme-linked immunosorbent assay (ELISA).Reactive oxygen species (ROS) and nitric oxide (NO) were measured.RESULTS The survival ratio of tyrosine hydroxylase-immunoreactive (TH-ir) neurons in the substantia nigra pars compacta (SNpc) and DA content in the striatum were significantly reduced after a single intranigral dose of LPS (10 μg) treatment.However, the administration of PLA for 6 weeks resulted in a significant increase in the survival rate of TH-ir neurons in the SNpc and DA levels in the striatum compared to model group rats.Microglia was over-activated in SNpc after LPS injection.PLA treatment significantly suppressed microglial activation by comparing the average optical density of immunohistochemical staining of Iba-1.The levels of inflammatory cytokines, including TNF-α, IL-6 and IL-1β were decreased and the excessive production of reactive oxygen species (ROS) and nitric oxide (NO) was abolished after PLA treatment.Therefore, the behavioral dysfunctions induced by LPS were improved after PLA treatment.CONCLUSION This study suggests that PLA plays a significant role in protecting dopaminergic neurons against inflammatory reaction induced damage.