Tenuigenin Protects Dopaminergic Neurons from Inflammation‐Mediated Damage Induced by the Lipopolysaccharide

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive death of dopaminergic neurons in the substantia nigra pars compacta (SNpc). AIMS: To study if tenuigenin (TEN), the main active component of Polygala tenuifolia, can protect dopaminergic neurons from inflammation-mediated damage in vivo. METHODS: We observed the effects of TEN on lipopolysaccharide (LPS) induced PD model by behavioral analysis, high-performance liquid chromatography, immunohistochemistry and enzyme-linked immunoadsorbent assay, etc. RESULTS: We showed that a single intranigral dose of LPSs (10 μg) induced microglial activation, reduced the survival ratio of tyrosine hydroxylase-immunoreactive (TH-ir) neurons in the SNpc and reduced dopamine (DA) content in the striatum. Treatment with 300 mg/kg TEN once per day over 14 weeks improved the survival rate of TH-ir neurons in the SNpc to 75%, on the non-injected side. Treatment with 200 or 300 mg/kg TEN once per day over 14 weeks significantly improved DA levels in the striatum to 73% and 81% on the non-injected side, respectively. The excessive production of cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β, was abolished by TEN administration. CONCLUSION: Our results suggest that TEN may play a role in protecting dopaminergic neurons against inflammatory challenge.