Identifying melanogenesis inhibitors from Cinnamomum subavenium with in vitro and in vivo screening systems by targeting the human tyrosinase.

Tyrosinase is known to be the first two and rate-limiting enzyme in the synthesis of melanin pigments responsible for colouring skin, hair and eyes. Tyrosinase inhibition is one major strategy used to treat hyperpigmentation. In human skin melanocytes, the cellular tyrosinase inhibition was examined by the conversion of l-tyrosine and oxidation of l-DOPA to dopaquinone. We evaluated the skin pigmentation inhibitor effects with both in vitro and in vivo systems to find skin-whitening agents without cytotoxic concerns. First, linderanolide B and subamolide A were isolated from the stems of Cinnamomum subavenium and exhibited mushroom tyrosinase inhibition. Then, these two herbal compounds were proved to have good pigmentation inhibitory abilities at low doses and demonstrated free cytotoxicities to normal human skin cells and zebrafish system. With molecular docking, in a virtual model of human tyrosinase, linderanolide B and subamolide A displayed meta(l) -coordinating interactions with Cu(2+) ions. The results obtained from biological assays showed that linderanolide B and subamolide A possessed anti-tyrosinase properties, which exhibited potential for application in medical cosmetology.