Triptolide preserves cognitive function and reduces neuropathology in a mouse model of Alzheimer's disease.
Triptolide preserves cognitive function and reduces neuropathology in a mouse model of Alzheimer's disease.
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DOI：
10.1371/journal.pone.0108845
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Li L
中科院分区：
文献类型：
--
作者：
Cheng S;LeBlanc KJ;Li L
雷公藤甲素是一种广泛使用的中草药的主要生物活性成分，已被证明具有多种药理功能，包括体外与阿尔茨海默病(AD)相关的潜在神经保护作用。然而，雷公藤甲素对AD的体内治疗潜力还没有得到彻底的评估。在本研究中，我们观察了雷公藤甲素外周给药对已建立的AD模型APPsWE/PS1ΔE9(APP/PS1)小鼠AD相关行为和神经病理的影响。我们的结果表明，雷公藤内酯醇治疗两个月可以挽救APP/PS1小鼠的认知功能。免疫组织化学分析表明，雷公藤甲素治疗可显著减少治疗小鼠的淀粉样蛋白(Aβ，Aβ)沉积和神经炎症。与之前的体外研究结果相比，生化分析表明，雷公藤内酯醇处理对体内Aβ的产生途径没有显著影响。有趣的是，进一步的分析显示，雷公藤甲素治疗上调了胰岛素降解酶的水平，这是大脑中主要的Aβ降解酶，表明雷公藤甲素治疗通过促进Aβ的蛋白降解来减轻Aβ的病理。我们的研究结果表明，雷公藤甲素治疗可以改善AD的关键行为和神经病理改变，提示雷公藤甲素可能是一种潜在的AD治疗药物。
Triptolide, a major bioactive ingredient of a widely used herbal medicine, has been shown to possess multiple pharmacological functions, including potential neuroprotective effects pertinent to Alzheimer's disease (AD) in vitro. However, the therapeutic potential of triptolide for AD in vivo has not been thoroughly evaluated. In the present study, we investigated the impact of peripherally administered triptolide on AD-related behavior and neuropathology in APPswe/PS1ΔE9 (APP/PS1) mice, an established model of AD. Our results showed that two-month treatment with triptolide rescued cognitive function in APP/PS1 mice. Immunohistochemical analyses indicated that triptolide treatment led to a significant decrease in amyloid-β (Aβ) deposition and neuroinflammation in treated mice. In contrast to previous findings in vitro, biochemical analyses showed that triptolide treatment did not significantly affect the production pathway of Aβ in vivo. Intriguingly, further analyses revealed that triptolide treatment upregulated the level of insulin-degrading enzyme, a major Aβ-degrading enzyme in the brain, indicating that triptolide treatment reduced Aβ pathology by enhancing the proteolytic degradation of Aβ. Our findings demonstrate that triptolide treatment ameliorates key behavioral and neuropathological changes found in AD, suggesting that triptolide may serve as a potential therapeutic agent for AD.
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影响因子：
5.3
作者：
Hickman, Suzanne E.;Allison, Elizabeth K.;El Khoury, Joseph
通讯作者：
El Khoury, Joseph
影响因子：
6
作者：
Coraci, IS;Husemann, J;El Khoury, JB
通讯作者：
El Khoury, JB
影响因子：
3.3
作者：
Kizelsztein, Pablo;Komarnytsky, Slavko;Raskin, Ilya
通讯作者：
Raskin, Ilya
影响因子：
4.7
作者：
Jaeger, Sebastian;Leuchtenberger, Stefanie;Pietrzik, Claus U.
通讯作者：
Pietrzik, Claus U.
DOI：
10.2174/187152710791012071
发表时间：
2010-04
期刊：
CNS & neurological disorders drug targets
影响因子：
--
作者：
Mandrekar-Colucci S;Landreth GE
通讯作者：
Landreth GE