| Summary: | 博士 === 國立臺灣大學 === 生物化學暨分子生物學研究所 === 95 === Tea is the most consumed drink in the world containing many compounds particularly polyphenols shown to reduce the risk of a variety of diseases in epidemiological studies. In the present study, we demonstrated the possible preventive mechanisms of tea polyphenols on Alzheimer''s disease and metabolic syndrome model. In part I, the results deminstrated that treatment with EGCG reduced the Aβ levels by enhancing endogenous APP nonamyloidogenic proteolytic processing in Aβ-induced AD model both in vitro and in vivo. Moreover, our results indicated that the neuroprotective action of EGCG may take place through c-Abl inhibition other than the promotion of APP nonamyloidogenic proteolysis. Part II demonstrated a possible mechanism for the antidiabetic effects of EGCG. As insulin resistance is a primary characteristic of type 2 diabetes resulting from hyperglycemia defects in insulin signals transduction, the aim of this study was to investigate the effects of EGCG on the insulin signaling pathway under high glucose. The results showed that high glucose downregulates IRS signaling activity, and subsequently repress hepatic glucose uptake and utilization by suppressing Akt activity. However, the EGCG supplementation alleviates this insulin signaling blockade by improving the function of IRS molecules, establishing a new molecular mechanism for antidiabetic activities of tea. In part III, the study examined why tea polyphenols have inhibitory effects on liver fat accumulation of hepatic cells. The results demonstrated that the tea compounds theaflavins significantly reduced hepatic lipid content, suppressed fatty acid synthesis both in vitro and in vivo. Furthermore, theaflavins also inhibited ACC activities by stimulating AMPK through LKB-1 and ROS pathway. The above-listed observations reveal that tea polyphenols indeed inhibit Aβ-induced neurotoxicity and display some antidiabetic benefits. Our results suggest that tea polyphenols show protection effects in the target cells and may be useful for the prevention of these diseases.
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