博士 / 國立臺灣大學 / 微生物與生化學研究所 / 95 / Recently, the Monascus research was gradually popular. The function of Monascus was possessed of antioxidant activity, cancer prevention and antifatigue in addition to anti-hypercholesterolemic and hypotensive effect. Monascus fermented product will be developed as a multi-functional food in the future. Taiwan has been gradually turned into a geriatric society. Therefore, the geriatric disease was respected by people, and senile dementia (also called Alzheimer’s disease (AD)) was major one of the diseases. Amyloid β-protein (Aβ) is the principal proteinaceous compound of amyloid plaques in brain of AD patients. Deposition of Aβ is expressed with increasing cholesterol concentration, decreasing neurotransmitter and serious oxidative stress and inflammatory response. Recently, one epidemiological study suggests that statin therapy may provide protection against AD. According as monacolin K is one of the statin compounds, and Monascus fermented products γ-aminobutyric acid (GABA) and antioxidant are possible to prevent AD development. Therefore, we considered that AD prevented and improved by Monascus was a feasibility study. The goal of this study is to develop a novel Monascus functional food with prophylactic effect on AD pathogenesis. The purpose of first section is to search and establish the optimal Monascus strain, and evaluate the potential for developing as a functional food. The evaluation of lowering AD risk factors and ameliorating impairment of memory and learning ability in AD rat model would be further carried out in the second section.
First, the analysis method of monacolin K and citrinin is set up in order to screen and examine the optimal red mold rice (RMR). In the result, citrinin (CT), monacolin K lactone form (MKL) and monacolin K acid form (MKA) are extracted using the same extraction method, and are then separated in a reverse phase C18 column. The elution from the C18 column is then passed through a UV detector and introduced directly into the fluorescence detector. As shown in the result, higher recovery rate of CT, MKL, and MLK are yielded from RMR powder by extracting with 95% ethanol (10 mL) at 60°C for 30 minutes. The peaks of CT, MKL, and MKA can be clearly separated from any noise peaks by isocratic elution with optimum mobile phase, acetonitrile-water-trifluoroacetate (55:45:0.05). In the development of Monascus strain, Monascus purpureus NTU 568 was selected from the mutants of M. purpureus HM 105 because it could produce high monacolin K production at 9,500 mg/kg. Such a Monascus species with high monacolin K productivity has never been published in the reference according to our view. M. purpureus NTU 568 was proven that it could perform stable production of secondary metabolite and well antioxidative ability. Regarding the hypolipidemia effect of M. purpureus NTU 568 fermented RMR, oral administration of RMR significantly lowers serum total cholesterol (TC), triglyceride (TG), and low density lipoprotein cholesterol (LDL-C), and does not result in liver damage.
In the results of RMR on repressing Aβ-induced neurotoxicity, monacolin K of RE fermented by M. purpureus NTU 568 (RE 568) represses Aβ40 toxicity via repressing small G-protein-mediated inflammation in PC12 cell. RE 568 also exhibits more robust anti-oxidative ability on the protection against Aβ-induced oxidative stress. Importantly, stronger effects on repressing the Aβ40-induced cell death, inflammation, and oxidative stress are performed by RE 568 than that by the equal levels of lovastatin, which results from a synergism mechanism made up of monacolin K, antioxidants and anti-inflammatory agents. The effects of dietary administration of RMR on memory and learning abilities are confirmed in an animal model of AD rats infused with Aβ40 into cerebral ventricle. The in vivo results indicate that RMR administration potently reverses the memory deficit in the memory task. Aβ40 infusion increases acetylcholinesterase (AChE) activity, reactive oxygen species, and lipid peroxidation, and decreases total antioxidant status and superoxide dismutase activity in brain, but these damages were potently reversed by RMR administration and the protection were more significant than that of lovastatin administration. In addition, these neuroprotection provided by RMR would lead to the prevention of Aβ40 accumulation in hippocampus. Regarding the section of RMR on repressing the formation of Aβ and related AD risk factors, PC-12 cell and IMR-32 cell are used as an in vitro cell model because of the expression of amyloid precursor protein (APP). Mevalonate and cholesterol supplementation would significantly enhance Aβ and soluble amyloid precursor protein α-secretase cleaved fragment (sAPPα) secretion in PC-12 cell and IMR-32 cell. Importantly, RE 568 can exhibit stronger effect on repressing cholesterol-mediated Aβ and sAPPβ secretion than lovastatin. At the same time, neuroprotective factor— sAPPα can be increase by RE 568 supplementation. In addition, RE 568 would repress the activity of β-secretase and indirectly inhibit Aβ secretion. In the in vivo results, orally administered RMR potently reversed the memory deficit in the water maze and passive avoidance tasks. Although Aβ40 infusion and cholesterol feeding caused great damage in brain involved in the increase of AChE activity, oxidative stress, and inflammation, the damage was potently reversed by RMR administration. Regarding the cholesterol diet-raised risk factor, RMR administration reduces brain cholesterol levels, apolipoprotein E (ApoE) expression, and β-secretase activity in cerebral cortex and hippocampus, and finally represses Aβ40 accumulation and stimulates sAPPα formation in hippocampus. Daily food supplement—RMR is the first to be applied to repress the formation of AD risk factors and ameliorate impairment of memory and learning ability. Importantly, RMR have an advantage over lovastatin for the prophylaxis of AD pathogenesis. We hope this study will be a great benefit to the development of Monascus functional food on the prophylaxis of AD.
| Identifer | oai:union.ndltd.org:TW/095NTU05381031 |
| Date | January 2007 |
| Creators | Chun-Lin Lee, 李俊霖 |
| Contributors | 潘子明 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 238 |
Page generated in 0.1255 seconds