厚朴酚和厚樸酚及其組合通過抑制神經炎症和突觸功能障礙改善TgCRND8小鼠的認知障礙 (Honokiol, Magnolol and Their Combination Ameliorate Cognitive Impairments in TgCRND8 Transgenic Mice via Modulating Amyloid Pathology, Neuroinflammation and Synaptic Dysfunction)
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香港中文大學研究人員

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摘要Magnolol (MN) and honokiol (HN) are two ligands isolated from Magnolia officinalis, and can cross the blood-brain barrier. MN and HN have been reported to improve the memory and learning deficits in several animal models of Alzheimer’s disease (AD). However, the anti-AD action mechanism are still unclear. In this study, we aimed to investigate the cognitive deficits improving effects of MN and HN, and their combination in TgCRND8 mice, a transgenic Alzheimer’s disease model. Male and female TgCRND8 mice were administered with HN (20 mg/kg), MN (20 mg/kg) or their combination (both 20 mg/kg) by oral gavage daily for 3 months, followed by assessing the spatial learning and memory functions with Radial Arm Maze test and Novel Object Recognition Test. Brain tissues were used to determine the changes in amyloid pathology, neuroinflammation and synaptic dysfunction using immunofluorescence, western blot and ELISA kits. Our results revealed that HN (20 mg/kg), MN (20 mg/kg) or their combination (both 20 mg/kg) significantly ameliorated cognitive deficits in TgCRND8 mice. In addition, HN (20 mg/kg), MN (20 mg/kg) or their combination (both 20 mg/kg) markedly reduced the levels of Aβ40, Aβ42 and TNF-α, IL-6 and IL-1β, and modulated the amyloid precursor protein (APP) processing and phosphorylation. HN, MN or their combination were also found to increase the protein expressions of postsynaptic density protein 93 (PSD93), PSD95, synapsin I (SYN1). Immunofluorescence showed that HN, MN or their combination reduced the Aβ deposition, as well as suppressed the activation of microglia (Iba-1) and astrocytes (GFAP) in the cerebral cortex and hippocampus of TgCRND8 mice. Furthermore, HN, MN or their combination was able to enhance the ratio of p-GSK-3β (Ser9)/GSK-3β and p-Akt (Ser473)/Akt in the brains of TgCRND8 mice. The results demonstrate that HN, MN and their combination possess anti-AD effects as evidenced by ameliorating cognitive impairment, and the underlying mechanisms involve the inhibition of Aβ generation and deposition, amelioration of synaptic dysfunction and neuroinflammation through modulating PI3K/Akt/GSK-3β signaling pathway in TgCRND8 transgenic mice. MN and HN are believed to have good potential for further development into therapeutic agents for AD treatment.

Acknowledgements
This work was supported by the General Research Fund from Research Grants Council of Hong Kong (project no. 14110814) and The Chinese University of Hong Kong Direct Grant (project no. 2017.076)
著者冼彥芳
會議名稱第八屆嶺南老年病暨健康管理論壇暨廣東省保健協會老年醫學與保健分會2019年年會暨廣東省健康管理學會老年醫學專業委員會2019年年會
會議開始日20.09.2019
會議完結日21.09.2019
會議地點廣州
會議國家/地區中國
出版年份2019
月份9
語言簡體中文

上次更新時間 2020-20-11 於 16:50