The aerial parts of Agastache rugosa are used as a food material and traditional medicine in Asia. A 50% ethanol extract exhibited potent xanthine oxidase (XO) inhibitory activity (IC50 = 32.4 µg/mL). To investigate the major components responsible for this effect, seven known compounds were identified from A. rugosa; among these, salvianolic acid B (2) was isolated from this plant for the first time. Moreover, acacetin (7) exhibited the most potent inhibitory activity with an IC50 value of 0.58 µM, lower than that of allopurinol (IC50 = 4.2 µM), which is commonly used as a XO inhibitor. Comparative activity screening revealed that the C6-bonded monosaccharides (3) or sugars substituted with acetyl or malonyl groups (4-6) are critical for XO inhibition when converted to aglycone (7). The most potent inhibitor (7) in the A. rugosa extract (ARE) exhibited mixed-type inhibition kinetics and reversible inhibition toward XO. Furthermore, the hydrolysis of ARE almost converted to an inhibitor (7), which displayed the highest efficacy; UPLC-qTof MS revealed an increased content, up to five times more compared with that before treatment. This study will contribute to the enhancement in the industrial value of ARE hydrolysates as a functional ingredient and natural drug toward the management of hyperuricemia and treatment of gout.
Keywords: Agastache rugosa; acacetin; gout; hyperuricemia; xanthine oxidase.