Microbiome-Metabolomics Reveals Endogenous Alterations of Energy Metabolism by the Dushen Tang to Attenuate D-Galactose-Induced Memory Impairment in Rats.

Sitong Ming,Qing Yang,Min Tang,Zhuang Zhang,Jifeng Wang,Hui Li,Xiaobo Qu,Xin Sui,Na Li,Wenjun Guo,Jing Li,Yanhong Zhang,Jianan Lin,Min He,Mo Kan,Xiaoran Liu

doi:10.1155/2021/6649085

Abstract

Aging affects the brain function in elderly individuals, and Dushen Tang (DST) is widely used for the treatment of senile diseases. In this study, the protective effect of DST against memory impairment was evaluated through the Morris water maze (MWM) test and transmission electron microscopy (TEM). A joint analysis was also performed using LC-MS metabolomics and the microbiome. The MWM test showed that DST could significantly improve the spatial memory and learning abilities of rats with memory impairment, and the TEM analysis showed that DST could reduce neuronal damage in the hippocampus of rats with memory impairment. Ten potential biomarkers involving pyruvate metabolism, the synthesis and degradation of ketone bodies, and other metabolic pathways were identified by the metabolomic analysis, and it was found that 3-hydroxybutyric acid and lactic acid were involved in the activation of cAMP signaling pathways. The 16S rDNA sequencing results showed that DST could regulate the structure of the gut microbiota in rats with memory impairment, and these effects were manifested as changes in energy metabolism. These findings suggest that DST exerts a good therapeutic effect on rats with memory impairment and that this effect might be mainly achieved by improving energy metabolism. These findings might lead to the potential development of DST as a drug for the treatment of rats with memory impairment.

Highlights

Aging is one of the most important factors involved in the gradual functional decline and structural degeneration of the brain and has been implicated in memory impairment, which is a major symptom of Alzheimer’s disease (AD) [1– 3]
The Morris water maze (MWM) test and transmission electron microscopy (TEM) analysis were used to assess the potential therapeutic effect of Dushen Tang (DST) against memory impairment, and the results suggested that DST exerted good protective effects against D-galactoseinduced memory impairment in rats
Our study found that the DST treatment promoted brain repair by participating protein synthesis for activating cAMP signaling pathway, especially by inhibiting the GNAI to activate the ADCY, following which to further activate its downstream target of cAMP and protein kinase A (PKA), as well as the cAMP response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in rat brain tissue [67]

Summary

Introduction

Aging is one of the most important factors involved in the gradual functional decline and structural degeneration of the brain and has been implicated in memory impairment, which is a major symptom of Alzheimer’s disease (AD) [1– 3]. Due to the rapid aging of the population, memory impairment seriously affects the quality of life of a large number of elderly individuals [4, 5]. Recent studies of cerebral energy metabolism have shown that mitochondrial dysfunction, oxidative stress, excessive levels of advanced glycation end products, and neurotoxicity are involved in the pathogenesis of memory impairment [6, 7]. Studies of memory impairment and relevant pathogenesis mechanisms could provide novel perspectives and targets for exploring new drug candidates and new therapy strategies and for evaluating the efficacy of drugs against aging and AD. Traditional Chinese herbal medicines have shown unique therapeutic effects on various diseases.

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