Investigating the Acute Effects of American Ginseng (Panax quinquefolius L.) on Naturally Aged Rats: A Study Using Serum and Brain Metabolomics Analysis

Background: American ginseng, scientifically known as Panax quinquefolius L. (Araliaceae), is a legally recognized medicinal and edible resource. Its roots serve dual purposes as both medicine and food. The primary active components are ginsenosides, which exhibit various pharmacological activities, including antioxidant and anti-fatigue effects. A single-dose administration in healthy adult models has demonstrated its regulatory effects on cardiac contraction, blood glucose levels, body temperature, metabolic parameters, and emotional cognition. However, the acute metabolic responses and their underlying mechanisms in naturally aged rats exposed to American ginseng remain unclear. Methods: This study employed an aged rat model to conduct comprehensive analyses of blood and brain tissues, aiming to characterize the physiological changes and underlying mechanisms associated with ageing following acute supplementation of American ginseng. Results: Findings revealed that a single exposure to American ginseng significantly improved the concentration levels of BNP, NE, E, Ang II, ALD, and 5-HT in serum, modulates the peripheral sympathetic nervous system and RAAS axis, inducing neurohumoral alterations. It also improved enzyme activity levels of SDH and LDH inducing a shift in the energy metabolism phenotype of aged rats; The improved MDA serum concentration levels indicate that oxidative damage was alleviated and the body’s antioxidant capacity was enhanced in aged rats. The results of neurotransmitter studies suggest that American ginseng can alter the content and ratios of amino acid and monoamine neurotransmitters in the brains of aged rats, modify the balance between excitatory and inhibitory neurotransmitters, and improve stress-related neurotransmitter levels. Compared with the aged control group, the serum and brain metabolomics identified 18 and 22 differentially expressed metabolites in the American ginseng group, respectively, primarily enriched in arginine and proline metabolism, glycine, serine, and threonine metabolism, cysteine and methionine metabolism, tyrosine metabolism, and alanine, aspartate, and glutamate metabolism. Conclusions: The aforementioned results demonstrate the multi-pathway metabolic perturbation characteristics induced by single exposure to American ginseng, providing novel experimental evidence for understanding the metabolic response patterns of aged organisms to exogenous stimulation from this medicinal herb and investigating its biological effects. These findings provide new scientific evidence to support the expanded functional positioning and health value of American ginseng.