碩士 / 國立陽明大學 / 生物藥學研究所 / 97 / Alzheimer’s disease (AD) is the most common neurodegenerative disease with the characteristic lesions of extracellular senile plaques and intracellular neurofibrillary tangles, in brain. Recent evidences suggested that inflammatory mechanisms represent a third characteristic which may significantly contribute to AD pathology. Therefore, anti-inflammation is recognized as a potential target for AD therapy. Besides, activation of microglia playing a key role involved in the process of AD-neuroinflammation is strongly suggested. To screen samples of Chinese herbal medicines used for reducing of Aβ-induced microglia-mediated neurotoxicity, microglia-derived cell line (BV2) was employed as a cell model, and lipopolysaccharides (LPS, the positive control stimulant), interferon-γ讪(microglia priming), Aβ42 oligomers and fibrils were used to activate BV2 cells. LPS and IFN-γ, but not Aβ42 oligomers or fibrils alone, activated BV2 to produce nitric oxide (NO) through increasing the protein level of inducible nitric oxide synthase (iNOS). Both the IFN-γ-induced increase of NO and iNOS levels were enhanced by Aβ42 fibrils, but not by the oligomers. Among 14 crude extracts of Chinese herbal medicines, CH-174-C (the ethanol/water extracts of Cudrania cochinchinensis) and CH-178-C (the ethanol/water extracts of Zanthoxylum ailanthoides) effectively reduced the NO production and iNOS expression mediated by Aβ42 fibrils plus IFN-γ讪or IFN-γ讪alone. On the other hand, rat primary mixed glia culture was employed to verify the effects of LPS, IFN-γ and Aβ42 oligomers on activating microglia. LPS, IFN-γ, Aβ42 oligomers plus IFN-γ, and Aβ42 oligomers alone effectively activated microglia by changing cell morphology from ramified to amoeboid. Aβ-mediated morphological change was also validated in the hippocampus of Aβ-intracerebroventricular injected ICR-1 mice. Finally, CH-174-C, CC-B (one pure compound isolated from CH-174-C) and CH-178-C effectively recovered the Aβ-mediated morphological change of microglia and promoted Aβ-clearance. Taken together, CH-174-C, CC-B and CH-178-C may be potential on AD therapy.
| Identifer | oai:union.ndltd.org:TW/097YM005603010 |
| Date | January 2009 |
| Creators | Feng-Yi Chiang, 江豐宜 |
| Contributors | Young-Ji Shiao, Jon, J.L. Ko, 蕭永基, 柯順龍 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 103 |
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