Dataset Information

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

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.

SUBMITTER: Wang J

PROVIDER: S-EPMC8175156 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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

Wang Jifeng J He Min M Guo Wenjun W Zhang Yanhong Y Sui Xin X Lin Jianan J Liu Xiaoran X Li Hui H Li Jing J Yang Qing Q Kan Mo M Zhang Zhuang Z Ming Sitong S Qu Xiaobo X Li Na N

BioMed research international 20210527

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 ...[more]

PMID: 34136571

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Project description:Geraniol (GE), an important ingredient in several essential oils, displayed pleiotropic biological activities through targeting multiple signaling cascades. In the current study, we aimed to examine the protective effect of GE on D-galactose (D-gal) induced cognitive impairment and explore the underlying mechanisms. Forty male Wistar rats (8 weeks old) were randomly categorized into 4 groups; Group I (saline + vehicle [edible oil]), group II (saline + geraniol) (100 mg/kg/day orally), group III (D-galactose) (100 mg/kg/day subcutaneously injected), and group IV (D-galactose + geraniol). Behavioral impairments were evaluated. Brain levels of malondialdehyde (MDA) and reduced glutathione (GSH) as well as superoxide dismutase (SOD) and acetylcholinesterase (AchE) activities were estimated. The levels of inflammatory markers [tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, and nuclear factor kappa beta (NF-kβ)], endoplasmic reticulum stress sensors [inositol requiring protein 1(IRE1) and protein kinase RNA-like endoplasmic reticulum kinase (PERK)], brain-derived neurotrophic factor (BDNF), and mitogen-activated protein kinases (MAPK) pathway were measured by ELISA. Also, hippocampal histopathological assessment and immunohistochemical analysis of glial fibrillary acidic protein (GFAP) and caspase-3 were performed. Glucose regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) mRNA expression and protein levels were assessed. GE effectively ameliorated aging-related memory impairment through increasing GSH, BDNF, Ach levels, and SOD activity. Additionally, GE treatment caused a decrease in the levels of MDA, inflammatory mediators, and ER stress sensors as well as the AchE activity together with concomitant down-regulation of GRP78 and CHOP mRNA expression. Moreover, GE improved neuronal architecture and rat's spatial memory; this is evidenced by the shortened escape latency and increased platform crossing number. Therefore, GE offers a unique pharmacological approach for aging-associated neurodegenerative disorders.

Project description:IntroductionDiabetic cognitive impairment(DCI) presents as a central nervous complication of diabetes especially among aging population. Melatonin (MEL) is known for its antioxidant and anti-inflammation effects in neuroprotective aspects. Recent evidence has demonstrated that the gut microbiome plays a key role in DCI by modulating cognitive function through the gut-brain crosstalk. MEL has been shown to modulate gut microbiota composition in diabetic model. However, the underlying mechanism through which the gut microbiome contributes to DCI remains unclear. This study aims to investigate the effect and mechanism of MEL in attenuating DCI in relation to regulating the gut microbiome and metabolomics.MethodsCognitive and memory function were assessed by the Morris water maze test, histopathological assessment of brain tissues, and immunoblotting of neuroinflammation and apoptosis. The levels of serum tumor necrosis factor-α (TNF-α) and Interleukin-18 (IL-18) were measured by enzyme-linked immunoassays to reflect the circulatory inflammation level.16S rRNA microbiome sequencing analysis was performed on control mice(db-m group), diabetic mice(db-db group) and MEL-treated diabetic mice(db-dbMEL group). Gut metabolites changes were characterized using liquid chromatography tandem mass spectrometry (LC-MS/MS).ResultsOur study confirmed that MEL alleviated diabetes-induced cognition and memory dysfunction. MEL protected against neuroinflammation and apoptosis in hippocampus of db-db mice. MEL corrected the increased abundance of Bacteroides and Dorea and the reduced abundance of Prevotella in db-db mice. The vast majority of differential metabolites among the three groups were lipids and lipid-like molecules. MEL significantly restored the reduced levels of pyruvate and lactic acid.DiscussionOur results supported the use of MEL as a promising therapeutic agent for DCI, in which the underlying mechanism may be associated with gut microbiome and metabolomics regulation.

Dataset Information

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

Publications

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

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