| Summary: | 碩士 === 國立臺灣大學 === 生化科技學系 === 102 === Alzheimer’s disease (AD) is a progressive neurodegenerative disorder mostly affecting the population of above 65 years of age. AD patients suffer from many cognitive abilities losses such as memory loss, language disability and behavior dysfunction, etc, and seriously affected their quality of life and social relationship. The most important pathology of AD is Amyloid β (Aβ) deposit, and Aβ causes oxidative stress and apoptosis in neuron, which is considered as the major reason for AD. Now lots of new drugs or health food in development begin with Aβ as the target, including decreasing levels and oxidative stress. Traditional Chinese herbal medicine has been used for thousands of years in the disease, in recent years, it developed to improve Alzheimer''s disease. Among them, Ginkgo biloba extract, the most successful development has been widely used as health foods in Europe and U.S.
According to the experimental results of our laboratory, Centella asiatica and Ziziphi spinosae semen have the abilities to protect rat and neuron in animal model and cell model. This study tries to find the effective compounds and research for the anti-oxidative ability and anti-aoptosis anbility.
At first, we identify Centella asiatica and Ziziphi spinosae semen by appearance and microscope. Then our study established the Aβ25-35-induced damage in differentiated PC12 cells as a cell model to discuss the protective effect of effective compounds in Centella asiatica and Ziziphi spinosae semen, and dive into the anti-oxidative stress and apoptosis. The experimental results show that the abundant component, madecoside (MS) and asiaticoside (AS) in Centella asiatica and the jujuboside A (JA) in Ziziphi spinosae semen, can reduce Aβ25-35 induced cytotoxicity. Co-culture the three substances with Aβ25-35 in 6 hr, and test the antioxidant capacity, we found they can improve both reactive oxygen species (ROS) and glutathione/glutathione disulfide (GSH/GSSG), enhance the activity of catalase (CAT), but only MS can enhance the activity of glutathione peroxidase (GPx) , and AS and JA can enhance the activity of superoxide dismutase (SOD). Those results show that they have antioxidant capacity by different ways.
Apoptosis can be divided into two pathways, death receptor pathway and mitochondrial pathway. In death receptor pathway, ligands activate caspase-8, and then activate caspase-3, in the end they induce apoptosis. In mitochondrial pathway, stress activates caspase-9, and then activates caspase-3, in the end they induce apoptosis. In our study, we find MS and JA have better anti-apoptosis abilities, and they can regulate death receptor pathway and mitochondrial pathway. But AS has poor effect, it can only regulate death receptor pathway. This study shows that MS and JA may be the effective compound in Centella asiatica and Ziziphi spinosae semen, and can improve Alzheimer''s disease by enhancing the activities of antioxidant enzymes and reducing apoptosis.
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