Neuroprotective Mechanism of Diosgeninon Lipopolysaccharide Induced Neurotoxicity

• Main Authors: Ssu-Chieh Tu, 杜思潔
• Other Authors: Ting-Yu Chin
• Format: Others
• Language: zh-TW
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/36180368772402236051

碩士 === 中原大學 === 生物科技研究所 === 100 === Microglial activation and inflammation mediated neurotoxicity are thought to be played a vital role in pathogenesis of neurodegenerative diseases such as Parkinson’s disease. Activated microglia results in secretion of various pro-inflammatory cytokines and neurotoxic mediators, which may contribute to neuronal cells death. Thus, a therapeutic strategy to reduce cytokine expression in microglia would be neuroprotective. Diosgenin from Chinese yam is the major steroid sapogenin, which has potential anti-inflammatory properties. In this study, we investigated whether diosgenin can be used to protect neurons from lipopolysaccharide (LPS)-induced neuro-inflammation. The results showed pre-treatment of midbrain-mixed culture with diosgenin reduced LPS-induced damage in dopamine neuronal dendrite. In addition, the mRNA expression level of tumor necrosis factor (TNF)-α and inducible NOS (iNOS) induced by LPS was decreased. Further analysis of cascade signaling events mediating the anti-inflammatory effects and the consequent neuroprotection of diosgenin indicates the involvement of the ERK1/2 pathway. Similarly, attenuated dopamine neurons loss and brain neuronal damage triggered by LPS were examined by immunohistochemistry staining, respectively, in pretreated diosgenin animal model. These results imply that diosgenin has anti-inflammatory and neuroprotective effects on modulating microglia activation by inhibiting LPS-induced neuro-inflammation and reducing the mRNA expression level of pro-inflammatory factors.