野生藍莓酒精粗萃物改善β澱粉樣蛋白誘導的神經功能障礙

失智症為神經退化性疾病，其特徵為記憶力減退、認知功能衰退及習慣改變。根據國際失智症協會統計，2020年全球超過5500萬的人患有失智症，推估2050年人數增至1億5200萬人。失智症最常見的類型為阿茲海默症（AD），佔失智症約七成。β澱粉樣蛋白（Aβ）與AD初期密切相關，其堆積在腦部造成粒線體功能障礙、突觸減少及神經元凋亡。藍莓有‘超級水果’之稱，其富含多酚，如花青素、類黃酮及酚酸。先前研究發現藍莓對健康有益，如抗癌、抗肥胖和神經保護等。本研究擬探討野生藍莓80%酒精粗萃取物改善HT-22神經元細胞之存活、粒線體功能和突觸可塑性。本實驗評估之指標包含野生藍莓萃取物對神經的保護（4’, 6-diamidino-2-phenylindole（DAPI），caspase-3 和cleaved caspase-3）、 改善粒線體（dihydroethidium （DHE）& JC-1，peroxisome proliferator-activated receptor-gamma coactivator-1alpha （PGC-1α），sirtuin 1（Sirt1）和nuclear factor erythroid 2-related factor 2（Nrf2））及突觸功能（neurexin-2 & 3, neuroligin-2，postsynaptic density protein-95（PSD-95），brain-derived neurotrophic factor (BDNF)和insulin-like growth factor 1（IGF-1）)。結果顯示，野生藍莓80%酒精萃取物可以顯著保護HT-22細胞免受Aβ毒性影響並改善粒線體功能。另外，改善突觸相關mRNA表現，支持其可改善突觸功能。野生藍莓酒精粗萃物之綠原酸可改善粒線體功能並有保護HT-22細胞免受Aβ毒性的趨勢。由本研究可知，野生藍莓粗萃物可減少Aβ毒性和神經元凋亡並改善粒線體和突觸功能，而綠原酸可能是改善因Aβ誘導的粒線體功能障礙及具有減少神經元凋亡趨勢的貢獻成分之一。

Dementia is a neurodegenerative disease characterized by memory loss, cognitive decline, and behavioral changes. According to the Alzheimer's Disease International (ADI), more than 55 million people worldwide were living with dementia in 2020, and this number is projected to rise to 152 million by 2050. Alzheimer's disease (AD) is the most common form of dementia, accounting for approximately 70% of all cases. Amyloid beta (Aβ) is closely associated with the early stages of AD, and its accumulation in the brain leads to mitochondrial dysfunction, synaptic loss, and neuronal apoptosis. Blueberries, often referred to as a “superfruit” are rich in polyphenols such as anthocyanins, flavonoids, and phenolic acids. Previous studies have shown that blueberries offer various health benefits, including anti-cancer, anti-obesity, and neuroprotective effects. This study aims to investigate the effects of wild blueberry 80% ethanol crude extract on the survival, mitochondrial function, and synaptic plasticity of HT-22 neuronal cells. The evaluated indicators include neuroprotection (4',6-diamidino-2-phenylindole (DAPI), caspase-3, and cleaved caspase-3), mitochondrial function (dihydroethidium (DHE) and JC-1 staining, peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α), sirtuin 1 (Sirt1), and nuclear factor erythroid 2-related factor 2 (Nrf2)), and synaptic function (neurexin-2 & -3, neuroligin-2, postsynaptic density protein-95 (PSD-95), brain-derived neurotrophic factor (BDNF), and insulin-like growth factor 1 (IGF-1)). The results showed that wild blueberry extract significantly protected HT-22 cells from Aβ-induced toxicity and improved mitochondrial function. Additionally, it enhanced the expression of synapse-related mRNA, supporting its role in improving synaptic function. The chlorogenic acid (CGA), a key component of crude ethanol extract of wild blueberry, might improve mitochondrial function and exhibit a protective trend against Aβ toxicity in HT-22 cells. Therefore, wild blueberry crude extract could reduce Aβ toxicity and neuronal apoptosis while enhancing mitochondrial and synaptic function. CGA alleviated Aβ induced mitochondrial dysfunction and showed a potential contributor in reducing neuronal apoptosis.