富含槲皮素-3-O-葡萄糖醛酸苷之荷葉萃取物藉由促進海馬回神經新生及抑制凋亡改善認知障礙

Miquelianin-enriched Nelumbo nucifera leaf extract ameliorates cognitive impairment via promoting neurogenesis and inhibiting apoptosis in hippocampus

林長楙(Chang-Mao Lin)

指導教授 ： 王朝鐘

共同指導教授 ： 許立松(Li-Sung Hsu)

中山醫學大學/醫學院/醫學研究所/碩士(2022年)

https://doi.org/10.6834/csmu202200083

摘要

老齡化一直是全世界的熱門問題，越來越多的人患有認知障礙甚至是神經退化性疾病，認知障礙又分為退化型、血管型及其他因素導致的認知障礙，其中退化型認知障礙為最常見，如阿茲海默症（Alzheimer’s disease, AD）和帕金森氏症（Parkinson’s disease, PD）。最近的流行病學研究表明，AD 與成年海馬回神經新生（adult hippocampal neurogenesis, AHN）缺陷以及氧化壓力、發炎反應和細胞凋亡有關。現在的治療方法只能延緩疾病的進程，而不是扭轉疾病的狀態。在我們之前的研究中，富含槲皮素-3-O-葡萄糖醛酸苷（miquelianin, quercetin 3-O-glucuronide, Q3G）之荷葉萃取物被證明具有抗氧化、抗發炎、抗細胞凋亡的作用。然而，富含Q3G之荷葉萃取物對認知障礙的影響仍未揭示。本研究調查了富含Q3G之荷葉萃取物是否可以促進 AHN 並抑制細胞凋亡以減輕認知障礙。 C57BL/6 小鼠用scopolamine（每週 3 mg/kg i.p.）誘導認知障礙，並給予0.5%荷葉水萃物（Nelumbo nucifera leaf water extract, NLWE）飲食和0.2%荷葉多酚萃取物（Nelumbo nucifera leaf polyphenol extract, NLPE）飲食持續6週。結果表明，透過Y迷宮試驗和腦源性神經滋養因子（brain-derived neurotrophic factor, BDNF）試驗評估，荷葉萃取物在動物模型中顯著恢復了scopolamine對認知障礙的影響。此外，在 NLWE 和 NLPE 餵食組中，DCX 和 NeuN 等神經新生相關蛋白的表達上升。另一方面，用scopolamine誘導SH-SY5Y細胞損傷，同時用NLWE和Q3G處理。透過流式細胞儀和西方墨點法證實，Q3G 顯著改善scopolamine引起的細胞凋亡並促進 DCX 和 NeuN 的表達。總之，NLWE和NLPE可以透過促進小鼠的AHN作用和抑制細胞凋亡，來達到恢復腦神經損傷之效果。

關鍵字

神經新生 ； 認知障礙 ； 東莨菪鹼 ； 荷葉萃取物 ； 細胞凋亡

並列摘要

Aging has been a popular issue worldwide, lately where more and more people have been suffering from cognitive impairment or even neurodegenerative diseases. There are three types of cognitive impairment, degenerative, vascular and other cognitive impairment. Degenerative cognitive impairment is the most common type, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Recent epidemiological studies indicate that AD is associated with the deficiency of adult hippocampal neurogenesis (AHN) as well as the oxidative stress, inflammation and apoptosis. The therapeutic treatments nowadays are only able to delay the course of the disease instead of reversing the state of the disease. In our previous studies, Miquelianin-enriched (quercetin 3-O-glucuronide, Q3G) Nelumbo nucifera leaf extract was proved to be anti-oxidant, anti-inflammation, anti-apoptosis agent. However, the effect of Q3G-enriched Nelumbo nucifera leaf extract on cognitive impairment remain unrevealed. This study investigated whether Q3G-enriched Nelumbo nucifera leaf extract could promote AHN and inhibit apoptosis to attenuate cognitive impairment. C57BL/6 mice were induced cognitive impairment with scopolamine (3 mg/kg i.p. weekly) and administered with the Nelumbo nucifera leaf water extract (NLWE, 0.5% diet) and the Nelumbo nucifera leaf polyphenol extract (NLPE, 0.2% diet) for 6 weeks. The results showed that NLWE significantly recovered the memory impairment by scopolamine in the animal model, evaluated by the Y-maze test and BDNF assay. In addition, the expression of neurogenesis-related protein such as DCX and NeuN were up-regulated in NLWE and NLPE treatment. On the other hand, SH-SY5Y cells were induced by scopolamine and simultaneously treated with NLWE and Q3G which is regarded as the main functional substance of Nelumbo nucifera leaves. Q3G notably ameliorated apoptosis caused by scopolamine and promoted the expression of DCX and NeuN, confirmed by flow cytometry and western blotting. In conclusion, NLWE and NLPE can recover neurodegeneration via promoting AHN and inhibiting apoptosis in scopolamine-induced mice.

並列關鍵字

neurogenesis ； cognitive impairment ； scopolamine ； Nelumbo nucifera leaf extract ； apoptosis

參考文獻

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