Tyrosinase Inhibitory Polyphenols from Roots of Morus lhou

• Published in: Journal of agricultural and food chemistry Vol. 57; no. 4; pp. 1195 - 1203
• Main Authors: Jeong, Seong Hun, Ryu, Young Bae, Curtis-Long, Marcus J, Ryu, Hyung Won, Baek, Yoon Su, Kang, Jae Eun, Lee, Woo Song, Park, Ki Hun
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 25.02.2009
• Subjects: Bioactive Constituents; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - isolation & purification; Enzyme Inhibitors - pharmacology; Flavonoids - isolation & purification; Flavonoids - pharmacology; Kinetics; Monophenol Monooxygenase - antagonists & inhibitors; Monophenol Monooxygenase - metabolism; Morus - chemistry; Morus - enzymology; Phenols - isolation & purification; Phenols - pharmacology; Plant Roots - chemistry; Polyphenols; slow-binding; Morus lhou; flavonoid; phenylbenzofuran; Tyrosinase
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf8033286

Twelve polyphenols (1−12) possessing tyrosinase inhibitory properties were isolated from the methanol (95%) extract of Morus lhou. 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 (IC50 values of 1.3, 1.2, and 7.4 μM). The potency of the inhibitors diminished with alkyl substitution 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, k 3 = 0.1966 min−1 μM−1, k 4 = 0.0082 min−1, and K i app = 0.0468 μM; diphenolase, k 3 = 0.0014 min−1 μM−1, k 4 = 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.