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

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive death of dopaminergic neurons in the substantia nigra pars compacta (SNpc). To study if tenuigenin (TEN), the main active component of Polygala tenuifolia, can protect dopaminergic neurons from inflammation-mediated damage in vivo. 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. 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. Our results suggest that TEN may play a role in protecting dopaminergic neurons against inflammatory challenge.