Comprehensive multiomics analysis of the effect of ginsenoside Rb1 on hyperlipidemia

Abstract

We analyzed the effects of ginsenoside Rb1 on hyperlipidemic in model mice. Using stool, plasma and hepatic tissue samples, we observed that the genera Blautia and Allobaculum were increased and Turicibacter was decrease in Rb1-treated mice as compared to untreated model mice. Ether lipid metabolism, glycerolipid metabolism, and glyoxylate and dicarboxylate metabolism were differentially enriched between the Rb1 and model groups. Lipidomics revealed 169 metabolites differentially expressed between the model and Rb1 groups in a positive ion model and 58 in a negative ion model. These metabolites mainly participate in glycerophospholipid, linoleic acid, and alpha-linolenic acid metabolism. The main metabolites enriched in these three pathways were phosphatidylcholine, diacylglycerol and ceramide, respectively. In a transcriptome analysis, 766 transcripts were differentially expressed between the Rb1 and model groups. KEGG analysis revealed lysine degradation, inositol phosphate metabolism, and glycerophospholipid metabolism to be the main enriched pathways. Multiomics analysis revealed glycerophospholipid metabolism to be a common pathway and phosphatidylcholine the main metabolite differentially enriched between the Rb1 and model groups. Results from fecal transplanted germ-free mice suggest that to suppress hyperlipidemia, Rb1 regulates gut microbiota by regulating the synthesis and decomposition of phosphatidylcholine in glycerophospholipid metabolism, which in turn decreases serum total cholesterol.

N-glycoproteomic analysis of Ginsenoside Rb1 on a hyperlipidemia rat model

“…Although our previous study has provided evidence of the therapeutical effect of Rb1 on hyperlipidemia in mice [15]. The mechanism of Rb1 on the modification level of plasma proteins in hyperlipidemia model has not been explored.…”

“…For example, Rb1 enhances atherosclerotic plaque stability by improving autophagy and lipid metabolism in macrophage foam cells [13], Rb1 improves leptin sensitivity in the prefrontal cortex in obese mice [14]. Our previous study found that Rb1 could potentially play a preventive role in hyperlipidemia [15]. However, the effect of Rb1 on N-glycosylation of plasma proteins in hyperlipidemia rats has not been studied.…”

Multi-Omics Reveals Inhibitory Effect of Baicalein on Non-Alcoholic Fatty Liver Disease in Mice

“…Lianqun et al found that alpha-linolenic acid metabolism was significantly downregulated in hyperlipidemia model mice. After ginsenoside Rb1 intervention, gut microbiota of mice was remarkably changed and alpha-linolenic acid metabolism was clearly upregulated ( Lianqun et al, 2021 ). In the research on human schizophrenia, Fan et al (2022) discovered a significant correlation between serum differential metabolites and differential intestinal bacteria between the patients with schizophrenia and the healthy individuals, while the metabolism of anti-inflammatory metabolites (such as alpha-linolenic acid) might be the regulatory target of gut microbiota.…”

Research Progress on Anti‐Inflammatory Mechanisms of Black Ginseng

“…In the process of regulating the intestinal flora, on the one hand, Dong [64] found that after oral administration of ginseng, the main ginsenosides were metabolized into deglycosylated ginsenosides through the intestinal microbiota, such as ginsenosides Ra, Rb1, Rb2, and Rc (which are metabolized into ginsenoside Rd mainly through the human intestinal microbiota), and then absorbed into the blood to exert its effect [65] . Alternatively, ginsenoside can regulate the catabolism of intestinal flora, especially ginsenoside Rb1, which can regulate intestinal flora by regulating the synthesis and decomposition of phosphatidylcholine in the glycerol phospholipid metabolic pathway through processes such as upregulation of the abundance of Blautia downregulation of the abundance of Turicibacter, etc [66] . Ginsenoside Rg1 can treat UC by improving the diversity of colonic microbiota and regulating the levels of Lachnospiraceae, Staphylococcus , Bacteroides and Ruminococcaceae‐UCG‐014 [67] .…”

“…[65] Alternatively, ginsenoside can regulate the catabolism of intestinal flora, especially ginsenoside Rb1, which can regulate intestinal flora by regulating the synthesis and decomposition of phosphatidylcholine in the glycerol phospholipid metabolic pathway through processes such as upregulation of the abundance of Blautia downregulation of the abundance of Turicibacter, etc. [66] Ginsenoside Rg1 can treat UC by improving the diversity of colonic microbiota and regulating the levels of Lachnospiraceae, Staphylococcus, Bacteroides and Ruminococcaceae-UCG-014. [67] Rk3 can intervene to repair intestinal barrier dysfunction by increasing the expression of tight junction proteins (zonula occludes-1, claudin, and occludin), effectively ameliorating the metabolic dysbiosis of the gut microbiota by significantly reducing the Firmicute/Bacteroidete ratio, thereby reducing colitis caused by chronic obesity.…”