Tyrosinase inhibitory activity of flavonoids from Artocarpus heterophyllous

Background: Tyrosinase is an oxidoreductase that is very important in medicine and cosmetics because the excessive production of melanin causes hyperpigmentation. The development of novel, effective tyrosinase inhibitors has long been pursued. In preliminary tests, we found that an extract of the wood of Artocarpus heterophyllous (AH) potently inhibited tyrosinase activity. Results: Two new flavonoids, artocaepin E (1) and artocaepin F (2), were isolated from the wood of AH, together with norartocarpetin (3), artocarpanone (4), liquiritigenin (5), steppogenin (6), and dihydromorin (7). Their structures were elucidated using one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) and mass spectrometry. The absolute configuration of 2 was determined from the circular dichroism (CD) spectrum. Artocarpanone (4) had the most potent tyrosinase inhibitory effect, with an IC50 of 2.0 +/- 0.1 mu M, followed by artocaepin E (1) and steppogenin (6), with IC50 values of 6.7 +/- 0.8 and 7.5 +/- 0.5 mu M, respectively. A kinetic investigation indicated that 1 showed competitive inhibition, with an inhibition constant (K-i) of 6.23 mu M. Conclusions: These results demonstrate that extracts of the wood of AH and its phytochemical constituents are potential sources for skin-whitening agents.