Purification reshapes systemic exposure and immunomodulation-mediated antiviral responses of licorice triterpenoids

Licorice is widely used in functional foods and food additives for its intense sweetness and diverse bioactivities, with triterpenoids considered important contributors to these properties. In this study, licorice triterpenoids were enriched using an eco-friendly macroporous resin method. Crude and purified extracts were comparatively evaluated in terms of chemical composition, blood-absorbed constituents, and protective effects under H1N1 challenge. Purification increased triterpenoid content, simplified the chemical matrix, and altered the profile of blood-absorbed constituents. Purified triterpenoids showed a modest advantage in alleviating H1N1-induced disease. Mechanistic analyses suggested that regulation of the cytokine-immune cell network, involving IL-6 and IL-1β modulation and partial restoration of M1/M2 macrophage and CD4⁺/CD8⁺ T-cell balance, may be involved in the protective effects of PLT. Overall, this study provides new insights into how purification influences the systemic exposure and bioactivity of licorice triterpenoids, thereby supporting their development as functional food ingredients.