Bomi Lee, Myeong-Sang Yu, Jae Gwang Song, Hyang-Mi Lee, Hyung Wook Kim, Dokyun Na
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引用次数: 0
Abstract
Recently, natural herbs have gained increasing attention owing to their comparatively low toxicity levels and the abundance of historical medical documentation regarding their use. Nevertheless, owing to a lack of knowledge regarding these herbs and their compounds, attempts to find those that could be beneficial for treating diseases have often been ad hoc; thus, there is now a growing demand for an in silico method to identify beneficial herbs. In this study, we present a computational approach for identifying natural herbs specifically effective in treating cognitive decline in Alzheimer's disease (AD) sufferers, which analyzes the similarities between herbal compounds and known drugs targeting AD-related proteins. Our in silico method suggests that Corydalis ternata can improve cognitive decline in AD sufferers. Behavioral tests with an AD mouse model for the confirmation of the in silico prediction reveals that C. ternata significantly alleviated the cognitive decline (memory and motor functions) caused by neurodegeneration. Further pathology analyses reveal that C. ternata decreases the level of Aβ plaques, reduces neuroinflammation, and promotes autophagy flux, and thus C. ternata can be clinically effective for preventing mild cognitive impairment during the early stages of AD. These findings highlight the potential utility of our in silico method and the potential clinical application of the identified natural herb in treating and preventing AD.
近来,天然草药因其相对较低的毒性水平和大量有关其用途的历史医学文献而受到越来越多的关注。然而,由于缺乏对这些草药及其化合物的了解,寻找有益于治疗疾病的草药的尝试往往是临时性的;因此,现在人们越来越需要一种硅学方法来识别有益的草药。在这项研究中,我们提出了一种计算方法,通过分析草药化合物与已知的针对注意力缺失症相关蛋白的药物之间的相似性,来确定对治疗注意力缺失症患者认知能力下降特别有效的天然草药。我们的硅学方法表明,C. ternata能改善AD患者的认知能力衰退。为了证实我们的硅学预测,我们用一种注意力缺失症小鼠模型进行了行为测试,结果表明 C. ternata 能明显缓解神经变性引起的认知能力下降(记忆和运动功能)。进一步的病理分析表明,蛇床子素能降低Aβ斑块的水平,减少神经炎症,促进自噬通量,因此蛇床子素在临床上可有效预防AD早期阶段的轻度认知障碍。这些发现凸显了我们的硅学方法的潜在效用,以及所发现的天然草药在治疗和预防AD方面的潜在临床应用。