Modified Huang-Lian-Jie-Du Decoction Ameliorates Aβ Synaptotoxicity in a Murine Model of Alzheimer's Disease
Modified Huang-Lian-Jie-Du Decoction Ameliorates Aβ Synaptotoxicity in a Murine Model of Alzheimer's Disease
复制标题
加减黄连解毒汤改善阿尔茨海默病小鼠模型中的 Aβ 突触毒性
DOI：
10.1155/2019/8340192
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发表时间：
2019-11-03
影响因子：
--
通讯作者：
Zhang, Yunlong
中科院分区：
文献类型：
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作者：
Liu, Yan;Du, Ting;Zhang, Yunlong
阿尔茨海默病（Alzheimer's disease，AD）是一种常见的神经退行性疾病，以认知功能障碍为主要特征，其治疗策略尚未完全阐明。黄连解毒汤是临床上广泛应用于治疗痴呆的著名中药方剂。最近，我们根据前人的研究和临床实践，提出了一种新的HLJDD的改良型（modified-HLJDD）。在这项研究中，我们表明修饰的HLJDD减轻了A β（1-42）寡聚体诱导的AD模型中的学习和记忆缺陷，并且我们通过UHPLC-Q-TOF-MS与HLJDD进行比较，证实了修饰的HLJDD溶液中的确切代谢物。使用基于GC-Q-TOF/MS的代谢组学，我们确定腺苷为潜在的重要代谢物，在AD模型中，修饰HLJDD负责调节能量代谢和突触可塑性。本研究还揭示了修饰HLJDD治疗AD的潜在机制可能涉及NMDA受体介导的神经递质传递和腺苷/ATP酶/AMPK级联反应。此外，我们还指出了AD模型中改良HLJDD治疗后的差异肠道微生物群，主要包括厚壁菌门、拟杆菌门、变形菌门和放线菌门。基于代谢组学分析与微生物群分析的相关性，我们阐明了Dorea是AD模型中经改良HLJDD治疗后腺苷影响最大的微生物群。因此，我们的研究表明，修饰HLJDD可能作为一个潜在的治疗药物在治疗AD。
Alzheimer's disease (AD) is a common neurodegenerative disease, characterized by cognitive dysfunction; however, the therapeutic strategies are not fully understood. Huang-Lian-Jie-Du-Decoction (HLJDD) is a famous traditional Chinese herbal formula that has been widely used clinically to treat dementia. Recently, according to previous study and our clinical practice, we generate a new modification of HLJDD (named modified-HLJDD). In this study, we indicated that modified-HLJDD attenuated learning and memory deficiencies in A beta(1-42) oligomer-induced AD model, and we confirmed the exact metabolites in modified-HLJDD solution, as compared with HLJDD by UHPLC-Q-TOF-MS. Using GC-Q-TOF/MS-based metabolomics, we identified adenosine as the potential significant metabolite, responsible for modified-HLJDD regulating energy metabolism and synaptic plasticity in AD model. We also revealed that the potential underlying mechanism of modified-HLJDD in AD model may involve NMDA receptor-mediated glutamatergic transmission and adenosine/ATPase/AMPK cascade. Moreover, we also indicated the differential gut microbiota which mainly involved Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria at the phylum level upon modified-HLJDD treatment in AD model. Based on the correlation of metabolomic analysis with microbiome analysis, we clarified that Dorea is the most affected microbiota with adenosine upon modified-HLJDD treatment in AD model. Thus, our study suggests that modified-HLJDD may serve as a potential therapeutic drug in treating AD.