To understand that 18β-Glycyrrhetic acid 3-O-mono-β-D-glucuronide (GAMG) showed better pharmacological activity and drug-like properties than 18β-Glycyrrhizin (GL); a rapid and sensitive HPLC-MS/MS method was established for the simultaneous determination of GAMG and its metabolite 18β-Glycyrrhetinic acid (GA) in rat plasma and tissues after oral administration of GAMG or GL. This analytical method was validated by linearity, LLOQ, specificity, recovery rate, matrix effect, etc. After oral administration, GAMG exhibited excellent C_max (2377.57 ng/mL), T_max (5 min) and AUC_0-T (6625.54 mg/L*h), which was much higher than the C_max (346.03 ng/mL), T_max (2.00 h) and AUC_0-T (459.32 mg/L*h) of GL. Moreover, GAMG had wider and higher tissue distribution in the kidney, spleen, live, lung, brain, etc. These results indicated that oral GAMG can be rapidly and efficiently absorbed and be widely distributed in tissues to exert stronger and multiple pharmacological activities. This provided a physiological basis for guiding the pharmacodynamic study and clinical applications of GAMG.

Novel kojic acid-tetrahydroisoquinoline hybrids (4a–4p) were designed and synthesized to address the need for safe tyrosinase inhibitors in food preservation. Compound 4c emerged as the most potent inhibitor, exhibiting 40-fold greater activity (IC₅₀ = 1.27 μM) than kojic acid. Kinetic studies identified 4c as a mixed-type inhibitor (K_i = 1.48 μM, K_is = 15.35 μM), with molecular docking revealing strong binding to tyrosinase's active site via copper chelation and hydrophobic interactions. Safety evaluations in zebrafish embryos and mammalian cell lines confirmed minimal cytotoxicity. Furthermore, 4c showed broad-spectrum antimicrobial activity against E. coli, S. aureus and B. cinerea. In practical applications, 4c effectively suppressed enzymatic browning in fresh-cut mushrooms. These results underscore 4c as a promising candidate for multifunctional food preservatives, combining anti-browning efficacy, microbial inhibition, and biocompatibility. This study provides a strategic framework for developing hybrid inhibitors to enhance food quality and safety.