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补骨脂提取物对阿尔茨海默病模型App小鼠认知功能障碍的预防作用

Preventive Effects of Psoraleae Semen Extracts on Cognitive Dysfunction in Alzheimer's Disease Model App Mice.

作者信息

Hiramatsu Genki, Mizutani Reina, Toume Kazufumi, Inada Yosuke, Sawahata Masahito, Uta Daisuke, Komatsu Katsuko, Kume Toshiaki

机构信息

Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.

Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.

出版信息

Biol Pharm Bull. 2025;48(1):75-79. doi: 10.1248/bpb.b24-00773.

Abstract

Oxidative stress and neuroinflammation accompanied by microglial activation are increased in Alzheimer's disease (AD) and contribute to the pathogenesis of AD. Nuclear factor erythroid-derived 2-related factor 2 (Nrf2) is a master transcription factor that acts as an endogenous defense mechanism against oxidative stress and inflammation and is a potential target for preventing AD. Psoraleae Semen (PS) reportedly has antioxidant and anti-inflammatory effects. This study aimed to examine the effects of PS extract (PSE) on Nrf2 activation and prevention of cognitive dysfunction in App AD model mice. The effects of PSE on antioxidant response element (ARE) activity and cytoprotection in PC12 cells and on microglial activation in BV-2 cells were evaluated. PSE showed high ARE activity and prevented 6-hydroxydopamine-induced cytotoxicity in PC12 cells. Moreover, PSE suppressed lipopolysaccharide-induced nitric oxide production in BV-2 cells. Oral administration of PSE prevented cognitive dysfunction in App mice without affecting motor function. Our results support that PSE can contribute to the development of new preventive and therapeutic agents for AD focusing on Nrf2 activation.

摘要

在阿尔茨海默病(AD)中,伴随着小胶质细胞激活的氧化应激和神经炎症会增加,并促进AD的发病机制。核因子红细胞衍生2相关因子2(Nrf2)是一种主要的转录因子,作为对抗氧化应激和炎症的内源性防御机制,是预防AD的潜在靶点。据报道,补骨脂(PS)具有抗氧化和抗炎作用。本研究旨在研究补骨脂提取物(PSE)对App AD模型小鼠中Nrf2激活和预防认知功能障碍的影响。评估了PSE对PC12细胞中抗氧化反应元件(ARE)活性和细胞保护以及对BV-2细胞中小胶质细胞激活的影响。PSE在PC12细胞中显示出高ARE活性,并预防了6-羟基多巴胺诱导的细胞毒性。此外,PSE抑制了BV-2细胞中脂多糖诱导的一氧化氮产生。口服PSE可预防App小鼠的认知功能障碍,而不影响运动功能。我们的结果支持PSE有助于开发以Nrf2激活为重点的AD新型预防和治疗药物。

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