Liuwei Dihuang Decoction Alleviates Cognitive Dysfunction in Mice With D-Galactose-Induced Aging by Regulating Lipid Metabolism and Oxidative Stress via the Microbiota-Gut-Brain Axis

Abstract

BackgroundAging is an important cause of cognitive dysfunction. Liuwei Dihuang decoction (LW), a commonly applied Chinese medicine formula, is widely used for the treatment of aging-related diseases in China. Previously, LW was confirmed to be effective in prolonging life span and reducing oxidative stress in aged mice. Unfortunately, the underlying mechanism of LW remains unclear. The aim of this study was to interpret the mechanism by which LW alleviates cognitive dysfunction related to aging from the perspective of the microbiota-gut-brain axis.MethodAll C57BL/6 mice (n = 60) were randomly divided into five groups: the control, model, vitamin E (positive control group), low-dose LW and high-dose LW groups (n = 12 in each group). Except for those in the control group, D-galactose was subcutaneously injected into mice in the other groups to induce the aging model. The antiaging effect of LW was evaluated by the water maze test, electron microscopy, 16S rRNA sequencing, combined LC–MS and GC–MS metabolomics, and ELISA.ResultsLiuwei Dihuang decoction ameliorated cognitive dysfunction and hippocampal synaptic ultrastructure damage in aging mice. Moreover, LW decreased Proteobacteria abundance and increased gut microbiota diversity in aging mice. Metabolomic analysis showed that LW treatment was associated with the significantly differential abundance of 14 metabolites, which were mainly enriched in apelin signaling, sphingolipid metabolism, glycerophospholipid and other metabolic pathways. Additionally, LW affected lipid metabolism and oxidative stress in aging mice. Finally, we also found that LW-regulated microbial species such as Proteobacteria and Fibrobacterota had potential relationships with lipid metabolism, oxidative stress and hippocampal metabolites.ConclusionIn brief, LW improved cognitive function in aging mice by regulating lipid metabolism and oxidative stress through restoration of the homeostasis of the microbiota-gut-brain axis.

Astaxanthin, <i>Haematococcus pluvialis</i> and <i>Haematococcus pluvialis</i> Residue Alleviate Liver Injury in D-Galactose-induced Aging Mice through Gut-liver Axis

“…Enriched abundance of Firmicutes and declined that of Bacteroidetes were reported to be positively related with liver injury 34) . Increased fecal proportion of F/B was reported in D-gal-induced aging model 35) , that is consistent with our results. Herein, astaxanthin and H. pluvialis residue notably decreased F/B, relative levels of Firmicutes and increased Bacteroidetes in the feces of D-gal treated mice.…”

Liuwei Dihuang formula ameliorates chronic stress-induced emotional and cognitive impairments in mice by elevating hippocampal O-GlcNAc modification

“…We found that the dominant gut constituents in the LW-treated group were Candidatus_Saccharimonas , Candidatus_Actinomarina , Mucispirillum , and Helicobacter at the genus level. The Candidatus Saccharimonas microflora could be significantly elevated ( Liu B. et al, 2022 ), and be related to inflammatory-related diseases ( Cruz et al, 2020 ). Moreover, Candidatus Saccharimonas was a known short-chain fatty acid (SCFA) producer, and its increased abundance affected intestinal pH ( Yao et al, 2022 ).…”

“…Liuwei Dihuang formula (LW) is a classical traditional Chinese medicine consisting of six herbs ( Zhou et al, 2016 ). In recent years, numerous studies have indicated that LW displayed ameliorative effects on the impairments of cognitive function induced by D-galactose ( Liu B. et al, 2022 ), β-amyloid ( Sangha et al, 2012 ), and senescence ( Huang et al, 2012 ). Moreover, further studies demonstrate that the active fraction and monomers of LW could also alleviate cognitive dysfunction via diverse mechanisms, including hippocampal transcriptome ( Wang et al, 2017b ), N-glycan ( Wang et al, 2017a ), neuroendocrine-immune system ( Wang et al, 2016c ), as well as intestinal microbiome ( Wang et al, 2019 ; Huang et al, 2022 ).…”

Dietary Catalase Supplementation Alleviates Deoxynivalenol-Induced Oxidative Stress and Gut Microbiota Dysbiosis in Broiler Chickens

“…Proteobacteria includes a mass of typical pathogens, such as Salmonella, Shigella, Klebsiella, and pathogenic Escherichia coli that can generate considerable toxins, thereby serving as a momemtous indicator of gut microbiota disturbance and health disorders of animals [44,45]. It has been documented that the expansions of Proteobacteria, Gammaproteobacteria, Enterobacteriales, Enterobacteriaceae, and Escherichia/Shigella in the gut could cause accumulation of lipopolysaccharide, rendering the occurrence of oxidative stress in animals [19,[46][47][48][49]. Herein, we detected negative correlations of the abundances of Proteobacteria, Gammaproteobacteria, Enterobacteriales, Enterobacteriaceae, and Escherichia/Shigella with both intestinal CAT activity and VH, demonstrating that the enrichments of these bacteria in the DON group conduced the simultaneous intestinal oxidative damage of broilers.…”