Development of herbal medicines for the treatment of Alzheimer’s disease: PC12 cells as a model / 以PC12細胞為模式開發抗阿滋海默症的中草藥

碩士 / 國立中興大學 / 生命科學院碩士在職專班 / 98 / Alzheimer’s disease (AD) is a progressive neurodegenerative disease in humans. Recent advances in the molecular medicine on this disease have greatly revealed the underlying mechanisms. The recent working hypothesis, namely β-amyloid (Aβ) hypothesis, suggests that erroneous processing of amyloid precursor protein (APP) by β- and γ-secretases produces Aβ and aggregation of Aβ or co-aggregation of Aβ with apolipoprotein E (apoE) triggers disease progression. The depositions of neurofibrillary tangles (NFT) and amyloid plaques are the hallmarks of AD pathology. In this study, naïve PC12 (nPC12) cells and nerve growth factor (NGF)-treated, differentiated PC12 (dPC12) cells were used as a cellular model to search for potential herbal medicines that may promote cell proliferation or differentiation. dPC12 cells were also treated with Aβ/apoE co-aggregates to mimic AD-induced neuronal damage and apoptosis. This model was used to search for bioactive fractions or components that may prevent or inhibit neuronal death in AD. Herbal medicines, reported in traditional Chinese medicine with implications or evidence in modern pharmacologic studies, were chosen for this purpose. EGb761, originated from Gingko biloba, and NGF were used as positive controls.
Results showed that the aqueous extracts of Rehmannia glutinosa, Citrus aurantium, Poria cocos, and Panax ginseng or the ethanolic extracts of Eucommia ulmoides promoted the nPC12 cell neurite out-growth, a marker of differentiation. The aqueous extracts of Acorus tatrinowii, Poria cocos, Morida officinalis, Schisandra chinensis, Panax ginserg, Acanthopanax senticosus, and Angelica sinensis or the ethanolic extracts of Huan Shao Tan and Rehmannia glutinosa promoted nPC12 cell proliferation. In the model that simulates AD progression (treatment with Aβ/ApoE4 aggregates), the aqueous and ethanolic extracts of Huan Shao Tan, and the ethanolic extracts of Acorus tatrinowii protected against Aβ-apoE4-induced cell damages. High-performance liquid chromatography (HPLC) was used to characterize the chemical profiles of bioactive fractions, which may help in future identification of bioactive compounds. In conclusion, this study provides valuable information that may shed light on future development of molecular pathogenesis-based novel herbal medicines for the treatment of AD.

Identiferoai:union.ndltd.org:TW/098NCHU5105060
Date January 2010
CreatorsYu-Ying Yu, 游裕瑩
ContributorsNien-Tai Hu, 胡念台
Source SetsNational Digital Library of Theses and Dissertations in Taiwan
Languagezh-TW
Detected LanguageEnglish
Type學位論文 ; thesis
Format89

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