Abstract
Based on accumulating evidence, Alzheimer's disease (AD) is related to hypercholesterolemia, gut microbiota, and host metabolites. GuanXinNing Tablet (GXN) is an oral compound preparation composed of two Chinese herbs, Salvia miltiorrhiza Bge. and Ligusticum chuanxiong Hort., both of which exert neuroprotective effects. Nevertheless, the effect of GXN on AD is unknown. In the present study, we investigated whether GXN alters cholesterol, amyloid-beta (Aβ), gut microbiota, serum metabolites, oxidative stress, neuronal metabolism activities, and apoptosis in an AD model rabbit fed a 2% cholesterol diet. Our results suggested that the GXN treatment significantly reduced cholesterol levels and Aβ deposition and improved memory and behaviors in AD rabbits. The 16S rRNA analysis showed that GXN ameliorated the changes in the gut microbiota, decreased the Firmicutes/Bacteroidetes ratio, and improved the abundances of Akkermansia and dgA-11_gut_group. 1H-NMR metabolomics found that GXN regulated 12 different serum metabolites, such as low-density lipoprotein (LDL), trimethylamine N-oxide (TMAO), and glutamate (Glu). In addition, the 1H-MRS examination showed that GXN remarkably increased N-acetyl aspartate (NAA) and Glu levels while reducing myo-inositol (mI) and choline (Cho) levels in AD rabbits, consequently enhancing neuronal metabolism activities. Furthermore, GXN significantly inhibited oxidative stress and neuronal apoptosis. Taken together, these results indicate that GXN attenuates AD via improving gut microbiota, host metabolites, and neuronal apoptosis.
Highlights
Alzheimer’s disease (AD), mainly manifested by memory and cognitive deterioration, is the most frequent neurodegenerative disease causing dementia in the elderly [1]
We investigated the effect of GuanXinNing Tablet (GXN) on blood lipid levels, behavior, histopathology, gut microbiota, serum metabolites, oxidative stress, neuronal metabolism activities, and apoptosis in this AD rabbit model to explore its ability to ameliorate AD, reveal the possible mechanism of action, and provide experimental evidence for GXN as a treatment to delay the progression of AD
We identified the main constituents of GXN using liquid chromatographymass spectrometry (LC–MS) analysis by referring to previous methods [13]
Summary
Alzheimer’s disease (AD), mainly manifested by memory and cognitive deterioration, is the most frequent neurodegenerative disease causing dementia in the elderly [1]. Approximately 50 million patients have AD worldwide, and this number is predicted to increase to 131 million by 2050 [3]. Since the main pathological hallmarks of AD are β-amyloid (Aβ) deposition and tau hyperphosphorylation, increasing research and development strategies of anti-AD drugs focus on these two processes [3]. Most drugs have failed in the clinical research phase [3], indicating that other pathways are involved in AD. Currently clinically used N-methyl D-aspartic acid receptor antagonists, Evidence-Based Complementary and Alternative Medicine cholinesterase inhibitors, and other AD drugs have limited efficacy with varying degrees of adverse reactions, usually increasing the difficulties associated with clinical medications for clinicians and patients [4, 5]. Currently clinically used N-methyl D-aspartic acid receptor antagonists, Evidence-Based Complementary and Alternative Medicine cholinesterase inhibitors, and other AD drugs have limited efficacy with varying degrees of adverse reactions, usually increasing the difficulties associated with clinical medications for clinicians and patients [4, 5]. erefore, in-depth studies of the mechanism of AD and its alternative treatment strategies are critical
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