Bioconverted Red Ginseng Protects Liver Functions and Alters Insulin Homeostasis-Associated Gut Microbiome Composition in Aged Mice.

BACKGROUND

Aging is associated with progressive functional deteriorations that affect the metabolic dysfunction in the liver and the alteration of the gut microbial environment. Red ginseng (RG) is one of the widely investigated ginseng products known for its antiaging properties, derived from its unique bioactive compounds known as ginsenosides.

OBJECTIVES

This study aimed to discover the potential antiaging effects of bioconverted red ginseng (BRG), a new RG product applied with enzymatic treatments, using an aged mouse model.

METHODS

Two different interventional regimes were employed: oral gavage administration and ad libitum intervention. For oral gavage study, 9-wk-old (Young) and 18-mo-old (Old) mice were orally injected with either distilled water or 300 mg/kg BRG for 4 wk (n = 10 per group). For ad libitum study, 19-mo-old mice were fed with a normal chow diet (NCD), NCD with 150 mg/kg BRG (BRG-Low; NCD+BRGL), or NCD with 300 mg/kg BRG (BRG-High; NCD+BRGH) for 14 wk (n = 9-10 per group). Liver tissues were harvested from each group for RNA sequencing, immunoblotting, and mRNA expression analyses. Fecal samples were collected, and 16S rRNA sequencing was conducted to profile gut microbiome composition.

RESULTS

The 4-wk BRG administration provided potential modulations in hepatic gene expression profiling in terms of mitigating age-driven liver cholestasis, as well as positive alterations in the gut microbial structure and composition. Moreover, the 14-wk BRG supplementation protected insulin homeostasis through activating the hepatic protein kinase B (AKT)/mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway and inhibiting glycogen synthase kinase (GSK)-3β in aged mice. In the meantime, BRG consumption altered insulin homeostasis-related microbiome structures by not only reducing the Firmicutes/Bacteroidetes ratio and relative abundance of opportunistic taxa, including Erysipelotrichaceae, but also increasing the enrichment of commensal bacteria, such as Muribaculaceae.

CONCLUSIONS

Taken together, this study highlights that BRG could be a promising antiaging functional food substance by maintaining insulin homeostasis and the gut microbial equilibrium.