| Summary: | 博士 === 國立臺灣大學 === 食品科技研究所 === 101 === Vascular dementia is a major type of senile dementia. Its prevalence is second to Alzeimer disease only. Phenolic acids occur widely in plant food materials with various functionalities. In this study, the object of is “Screening and confirmation of natural phenolic acids for their alleviative effect on vascular dementia in cell and animal models”. The screening was performed in an oxygen-glucose deprivation PC12 cell model, and followed with the confirmation in two-vessel occlusion forebrain ischemia model of rats. In the cell model, eight phenolic acids, including caffeic acid, chlorogenic acid, cinnamic acid, coumaric acid, ferulic acid, gallic acid, proto-catechuic acid and vanillic acid, in various concentrations between 12.5 and 200μm were used and the cytoprotective effects were evaluated. Gallic acid at 100μm was found to be the most cytoprotective, with a PC12 cell survival rate at 90.2 ± 4.1%, to inhibit the release of LDH enzyme, and to enhance cell autophagy via the release of calcium ions. Scanning electron microscopic observation confirmed that the enhancement in autophagy helps PC12 nerve cells to maintain its morphological integrity. A two-vessel occlusion model of rats was then used to further validate the alleviative effect of gallic acid on vascular dementia in vivo. Animal behavioral experiments, including passive avoidance performance and Morris water maze test, showed that gallic acid, at 10, 50, and 100mg/kg, is able to improve the memory and learning ability in rats with dose dependency. Immuohistochemical straining and the evaluation of biochemical parameters in serum and antioxidant enzymes activities in brain was performed to elucidate the safety of gallic acid intake and mechanism for gallic acid to improve vascular dementia. Based on the experiment data, we propose that gallic acid promotes TAS, SOD and GSH activities while decreases iNOS activity and TBARS levels in cortex and hippocampus. Immunohistochemical stain of brain tissue found that gallic acid downregulates HIF-1α expression while upreguilates Ki-67, Nrf2 and HO-1 expression, indicating that gallic acid may prevent vascular dementia via the promotion of nerve cell regeneration.
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