Comparative pharmacokinetics of total ginsenosides between young and aging mice

Ginsenosides, the primary bioactive constituents of ginseng, are widely recognized as popular natural products with anti-aging properties. However, they generally exhibit poor oral bioavailability. Moreover, existing pharmacokinetic studies have predominantly focused on young animal models, leaving a critical gap in understanding how aging alters the absorption, distribution, metabolism, and excretion of these compounds. This study aims to elucidate the multi-component pharmacokinetics and tissue distribution profiles of total ginsenosides following oral administration in both young and aging mice.

The validity of the aging mouse model was first confirmed through a series of physiological evaluations. A multiple reaction monitoring (MRM) technique was then employed to conduct comparative pharmacokinetic and tissue distribution analyses of 15 targeted ginsenosides after oral administration in young and aging mice.

Aging mice exhibited significantly higher systemic exposure (AUC) and markedly reduced clearance rates compared to their young counterparts. Tissue distribution analysis revealed the highest accumulation of ginsenosides in the liver, followed by the heart, kidneys, spleen, lungs, testes, and brain, confirming the liver as the primary metabolic site.

These findings demonstrate that aging increases systemic exposure, prolongs half-lives, and enhances tissue accumulation of ginsenosides. This study provides essential scientific evidence for the rational clinical application and dosage optimization of ginseng in aging populations.