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.

A Systematic Review of In Vivo Studies of the Efficacy of Herbal Medicines for Anti-Aging in the Last Five Years

“…As for the countries where the experiments were conducted, China had the most cases (n = 20) [ 8 , 9 , 13 , 15 , 16 , 19 , 23 , 26 , 27 , 28 , 29 , 30 , 32 , 36 , 38 , 39 , 46 , 47 , 48 , 49 ], followed by Japan (n = 8) [ 12 , 20 , 40 , 41 , 42 , 43 , 44 , 45 ], Korea (n = 6) [ 24 , 31 , 33 , 34 , 35 , 37 ] and Taiwan (n = 3) [ 21 , 22 , 23 ]. Thailand [ 18 ], the United States [ 17 ], Mexico [ 11 ] and Poland [ 25 ] were each associated with one study.…”

“…In herbal medicine extraction, 17 studies used water extraction [ 9 , 13 , 14 , 17 , 20 , 21 , 22 , 27 , 31 , 33 , 39 , 40 , 42 , 45 , 47 , 48 ]; 6 studies used ethanol [ 10 , 16 , 18 , 24 , 34 , 35 ]; and 2 studies used carbon dioxide fluid [ 23 , 26 ]. Three studies used a suspension of the herbal formula Guilingji [ 15 , 29 , 30 ].…”

“…One study did not report the route of administration [ 11 ]. Eighteen studies tested the dose of herbal medicine at a single concentration [ 11 , 13 , 17 , 18 , 19 , 20 , 21 , 24 , 28 , 31 , 37 , 38 , 39 , 40 , 42 , 46 , 48 , 50 ], and in 21 studies, 2 or 3 types of concentrations were tested [ 8 , 9 , 10 , 14 , 15 , 16 , 22 , 23 , 25 , 26 , 27 , 29 , 30 , 32 , 33 , 34 , 35 , 36 , 41 , 45 , 47 ]. The other two studies did not report the dosage used [ 12 , 44 ].…”

Gut Microbiota: Therapeutic Targets of Ginseng Against Multiple Disorders and Ginsenoside Transformation

“…In the rat ischemia/reperfusion model, ginsenoside Rb1 can increase the relative abundance of Lactobacillus and gamma-aminobutyric acid receptors to reduce the proinflammatory cytokines for the improvement of neuroprotection ( Chen et al., 2020 ). In the rats induced by D-galactose, ginseng decoction called Dushen Tang showed good curative ability for memory impairment by up-regulating Bacteroidetes and down-regulating Lactobacillus ( Wang et al., 2021 ). In the mice with Parkinson’s disease, the treatment with the extract from KRG can improve neuronal function and alleviate Parkinson’s symptoms by up-regulating the relative abundance of Eubacterium and down-regulating the relative abundances of Verrucomicrobia and Ruminococcus ( Jeon et al., 2020 ).…”

Potential roles of the gut microbiota in the manifestations of drug use disorders

“…Taken together, as a signaling molecule, lactic acid in astrocytes is important to the drug memory (80). Although little research provides the evidence that GM can directly affect drug memory, a previous study has shown that memory disorders in rats with elevated levels of lactic acid, an important biomarker, could be improved by correcting intestinal microbial disorders 10.3389/fpsyt.2022.1046804 (e.g., Lactobacilllus, Bacteroidales, and Bacteroides) (81,82). Therefore, future research on drug memory and reducing relapse may be carried out through GM therapy to interfere with the production and secretion of lactic acid.…”