1. Modified Huang-Lian-Jie-Du Decoction Ameliorates Aβ Synaptotoxicity in a Murine Model of Alzheimer’s Disease
- Author
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Weiye Lu, Ting Du, Wenlong Zhang, Lei Wen, Yun-Long Zhang, Xiangdong Sun, Linchao Qian, Zhichao Peng, Xiaoqin Zhu, Pingyi Xu, Chaojun Chen, Shu-Qiong Huang, and Yan Liu
- Subjects
Male ,Aging ,Article Subject ,Metabolite ,Pharmacology ,Gut flora ,Synaptic Transmission ,Biochemistry ,Mice ,chemistry.chemical_compound ,Metabolomics ,Alzheimer Disease ,medicine ,Animals ,Humans ,Dementia ,Microbiome ,lcsh:QH573-671 ,Amyloid beta-Peptides ,Neuronal Plasticity ,biology ,lcsh:Cytology ,business.industry ,Anti-Inflammatory Agents, Non-Steroidal ,AMPK ,Cell Biology ,General Medicine ,medicine.disease ,biology.organism_classification ,Adenosine ,Peptide Fragments ,Disease Models, Animal ,chemistry ,Synapses ,Synaptic plasticity ,business ,Research Article ,Drugs, Chinese Herbal ,medicine.drug - Abstract
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 Aβ1-42 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.
- Published
- 2019
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