Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Mar 1;29(5):1108.
doi: 10.3390/molecules29051108.

Ginsenoside Rb1, Compound K and 20(S)-Protopanaxadiol Attenuate High-Fat Diet-Induced Hyperlipidemia in Rats via Modulation of Gut Microbiota and Bile Acid Metabolism

Affiliations

Ginsenoside Rb1, Compound K and 20(S)-Protopanaxadiol Attenuate High-Fat Diet-Induced Hyperlipidemia in Rats via Modulation of Gut Microbiota and Bile Acid Metabolism

Kang-Xi Zhang et al. Molecules. .

Abstract

Hyperlipidemia, characterized by elevated serum lipid concentrations resulting from lipid metabolism dysfunction, represents a prevalent global health concern. Ginsenoside Rb1, compound K (CK), and 20(S)-protopanaxadiol (PPD), bioactive constituents derived from Panax ginseng, have shown promise in mitigating lipid metabolism disorders. However, the comparative efficacy and underlying mechanisms of these compounds in hyperlipidemia prevention remain inadequately explored. This study investigates the impact of ginsenoside Rb1, CK, and PPD supplementation on hyperlipidemia in rats induced by a high-fat diet. Our findings demonstrate that ginsenoside Rb1 significantly decreased body weight and body weight gain, ameliorated hepatic steatosis, and improved dyslipidemia in HFD-fed rats, outperforming CK and PPD. Moreover, ginsenoside Rb1, CK, and PPD distinctly modified gut microbiota composition and function. Ginsenoside Rb1 increased the relative abundance of Blautia and Eubacterium, while PPD elevated Akkermansia levels. Both CK and PPD increased Prevotella and Bacteroides, whereas Clostridium-sensu-stricto and Lactobacillus were reduced following treatment with all three compounds. Notably, only ginsenoside Rb1 enhanced lipid metabolism by modulating the PPARγ/ACC/FAS signaling pathway and promoting fatty acid β-oxidation. Additionally, all three ginsenosides markedly improved bile acid enterohepatic circulation via the FXR/CYP7A1 pathway, reducing hepatic and serum total bile acids and modulating bile acid pool composition by decreasing primary/unconjugated bile acids (CA, CDCA, and β-MCA) and increasing conjugated bile acids (TCDCA, GCDCA, GDCA, and TUDCA), correlated with gut microbiota changes. In conclusion, our results suggest that ginsenoside Rb1, CK, and PPD supplementation offer promising prebiotic interventions for managing HFD-induced hyperlipidemia in rats, with ginsenoside Rb1 demonstrating superior efficacy.

Keywords: bile acid metabolism; ginsenoside CK; ginsenoside PPD; ginsenoside Rb1; gut microbiota; hyperlipidemia.

PubMed Disclaimer

Conflict of interest statement

There are no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Effect of ginsenoside Rb1, CK and PPD treatment on body weight, hyperlipidemia and liver steatosis in HFD-fed rats. (A) The experimental design, (B) body weight (g), (C) body weight gain (%), (D) eWAT/BW (%), (E) liver/BW (%), (F) fasting blood glucose (mmol/L), (GJ) serum concentrations of TC, TG, HDL-C and LDL-C (mmol/L), (K) histological analysis for liver and epididymal adipose tissues (eWAT), and (LN) serum concentrations of TNF-α, IL-6 and IL-1β (ng/L). Values are the means ± SEMs. * p < 0.05, ** p < 0.01 and versus the HFD group, ns means no significantly difference.
Figure 2
Figure 2
Effects of ginsenoside Rb1, CK and PPD on gut microbiota structure in HFD-fed rats. (A) α diversity analysis, (B) PCoA analysis, (C) phylum-level analysis, (D) top 30 genus-level analysis, (E) heatmap showing the relative abundance of 21 genera significantly altered after ginsenoside Rb1, CK and PPD treatment, formula image representing more abundance in the Rb1, CK and PPD groups compared with the HFD group, formula image representing less abundance in the Rb1, CK and PPD groups compared with the HFD group, (F) change in the relative abundance of representative genera. Values are the means ± SEMs. * p < 0.05, ** p < 0.01 and *** p < 0.001 versus the HFD group, ns means no significantly difference.
Figure 3
Figure 3
Effects of ginsenoside Rb1, CK and PPD on the gut microbial community in HFD-fed rats. The cladogram of the linear discriminant analysis effect size (LEfSe) analysis for (A) Rb1 vs. HFD, (B) CK vs. HFD, and (C) PPD vs. HFD.
Figure 4
Figure 4
Effects of ginsenoside Rb1, CK and PPD on the relative expression of genes and proteins related to cholesterol metabolism and fatty acid metabolism in HFD-fed rats. (A) The relative expression of genes related to cholesterol metabolism and fatty acid metabolism. (B) The protein expression of PPARγ, ACC, FAS, PPARα, HSL, FXR and CYP7A1 in liver. Values are the means ± SEMs. * p < 0.05, ** p < 0.01 and *** p < 0.001 versus the HFD group, ns means no significantly difference.
Figure 5
Figure 5
Effects of ginsenoside Rb1, CK and PPD on BA metabolism in HFD-fed rats. (A) The total BA level in serum; (B) primary/unconjugate BA level in serum; (C) primary/conjugate BA in serum; (D) secondary/conjugate BA in serum; (E) the total BA level in liver; (F) primary/unconjugate BA level in liver; (G) primary/conjugate BA in liver; (H) secondary/conjugate BA in liver. Values are the means ± SEMs. * p < 0.05, ** p < 0.01 versus the HFD group, ns means no significantly difference.
Figure 6
Figure 6
The heatmap showed Pearson’s correlation coefficient with p < 0.05 between key gut microbes and BAs in the HFD, Rb1, CK and PPD groups. (A) The correlation between the top 20 genus and serum BAs in the HFD group, (B) the correlation between the top 18 genus and serum BAs in the Rb1 group, (C) the correlation between the top 20 genus and serum BAs in the CK group, and (D) the correlation between the top 20 genus and serum BAs in the PPD group. Red cells represent positive correlation and blue cells represent negative correlation.

Similar articles

References

    1. Leuti A., Fazio D., Fava M., Piccoli A., Oddi S., Maccarrone M. Bioactive lipids, inflammation and chronic diseases. Adv. Drug Deliv. Rev. 2020;159:133–169. doi: 10.1016/j.addr.2020.06.028. - DOI - PubMed
    1. Deprince A., Haas J.T., Staels B. Dysregulated lipid metabolism links NAFLD to cardiovascular disease. Mol. Metab. 2020;42:101092. doi: 10.1016/j.molmet.2020.101092. - DOI - PMC - PubMed
    1. Badmus O.O., Hillhouse S.A., Anderson C.D., Hinds T.D., Stec D.E. Molecular mechanisms of metabolic associated fatty liver disease (MAFLD): Functional analysis of lipid metabolism pathways. Clin. Sci. 2022;136:1347–1366. doi: 10.1042/CS20220572. - DOI - PMC - PubMed
    1. Lu X.Y., Shi X.J., Hu A., Wang J.Q., Ding Y., Jiang W., Sun M., ZAhao X., Luo J., Qi W., et al. Feeding induces cholesterol biosynthesis via the mTORC1–USP20–HMGCR axis. Nature. 2020;588:479–484. doi: 10.1038/s41586-020-2928-y. - DOI - PubMed
    1. Chiang J.Y.L. Bile Acid Metabolism and Signaling. Compr. Physiol. 2013;3:1191–1212. - PMC - PubMed
-