Discovery of a Highly Potent Tyrosinase Inhibitor, Luteolin 5-<i>O</i>-β-<scp>d</scp>-Glucopyranoside, Isolated from <i>Cirsium japonicum</i> var. <i>maackii</i> (Maxim.) Matsum., Korean Thistle: Kinetics and Computational Molecular Docking Simulation

Abstract

In the present study, the natural flavonoid luteolin 5-O-β-d-glucopyranoside isolated from the Korean thistle, Cirsium japonicum var. maackii (Maxim.) Matsum., for the first time, found to be a strong competitive inhibitor against mushroom tyrosinase (IC50 = 2.95 ± 0.11 μM, Ki = 3.02 μM for l-tyrosine; IC50 = 8.22 ± 0.18 μM, Ki = 11.56 μM for l-3,4-dihydroxyphenyl-alanine), which outperformed luteolin and 5-deoxy luteolin (3′,4′,7-trihydroxyflavone), showing noncompetitive and competitive inhibition only in l-tyrosine, respectively, emphasizing the importance of glycosylation at 5-OH position of luteolin. Furthermore, molecular modeling of luteolin 5-O-β-d-glucopyranoside showed strong H-bond interaction with Arg268 and peroxide ion (Per402) present between the copper ions. Additionally, the luteolin 5-O-β-d-glucopyranoside–tyrosinase complex was stabilized by electrostatic and hydrophobic interactions formed with key catalytic residues; however, in luteolin, these were lacking. Therefore, Cirsium maackii may act as an important anti-tyrosinase remedy because of the amount and potency of the active compounds luteolin 5-O-β-d-glucopyranoside and luteolin.