American Ginseng (Panax quinquefolius) Extracts (G1899) Ameliorate Immunosenescence via Regulation of T Cell Populations and Aging-Related Proteins in a Mouse Model Induced by D-Galactose and Tert-Butyl Hydroperoxide

Immunosenescence is characterized by an age-associated decline in immune function, particularly involving T-cell dysfunction, which increases susceptibility to infections and chronic diseases. This study investigated the anti-aging and immunomodulatory effects of American ginseng extract (G1899) using in vitro and in vivo models of aging. Cellular senescence was induced in HepG2 cells by D-galactose treatment, followed by exposure to G1899 (20 and 100 μg/mL). Senescence-associated markers were assessed to evaluate cellular aging. An aging mouse model was established in male C57BL/6 mice through intraperitoneal administration of D-galactose (500 mg/kg) and tert-butyl hydroperoxide (0.4 mmol/kg), and G1899 was orally administered at 400 mg/kg. Thymic immune cell subsets and aging-related protein expression were analyzed using flow cytometry and Western blotting. G1899 significantly reduced p21 expression and senescence-associated β-galactosidase activity in senescent HepG2 cells. In aging-induced mice, G1899 restored CD4⁺ and CD8⁺ T-cell populations, normalized naïve T-cell levels, and reduced anergic CD28-negative T cells. Furthermore, G1899 regulated the expression of key aging-related proteins, including FOXO1, Sirt1, p53, and CD38. These findings demonstrate that G1899 attenuates age-related immune alterations by restoring thymic T-cell homeostasis and regulating aging-associated molecular pathways.