Tyrosinase Inhibitory Polyphenols from Roots of Morus Ihou

摘要

Twelve polyphenols (1 -12) possessing tyrosinase inhibitory properties were isolated from the methanol (95%) extract of Morus Ihou. The isolated compounds consisted of four flavanones (1 -4), four flavones (5-8), and four phenylbenzofuranes (9-12). Moracin derivative 12 proved to be new a compound which was fully characterized. Compounds 1-12 were evaluated for both monophenolase and diphenolase (the two steps catalyzed by tyrosinase) inhibition to identify the structural characteristics required for mushroom tyrosinase inhibition. We observed that all parent compounds (1, 5, and 9) possessing an unsubstituted resorcinol group were highly effective inhibitors of monophenolase activity (IC_(50) values of 1.3, 1.2, and 7.4 μM). The potency of the inhibitors diminished with alkyl subst.tut.on on either the aromatic ring or the hydroxyl functions. Interestingly, flavone 5 was shown to possess only monophenolase inhibitory activity, but flavanone 1 and phenylbenzofuran 9 inhibited diphenolase as well as monophenolase significantly. The inhibitory mode of these species was also dependent upon the skeleton: phenylbenzofuran 9 manifested a simple competitive inhibition mode for monophenolase and diphenolase; on the other hand flavanone 1 (monophenolase, k3 = 0.1966 min~(-1) μM~(-1), k4 = 0.0082 mim~(-1) and K_i~(app) = 0.0468 μM; diphenolase, k3 = 0.0014 min~(-1) μM~(-1),K4 = 0.0013 min~(-1) and K_i~(app) = 0.8996 μM) and flavone 5 both showed time-dependent inhibition against monophenolase. Compound 1 operated according to the simple reversible slow binding model whereas compound 5 operated under the enzyme isomerization model.