| In vitro: |
| J Dermatol Sci. 2014 Oct;76(1):16-24. | | Depigmentation caused by application of the active brightening material, rhododendrol, is related to tyrosinase activity at a certain threshold.[Pubmed: 25082450] | Unexpected depigmentation of the skin characterized with the diverse symptoms was reported in some subjects who used a tyrosinase-competitive inhibiting quasi-drug, Rhododendrol. To investigate the mechanism underlying the depigmentation caused by Rhododendrol-containing cosmetics, this study was performed.
METHODS AND RESULTS:
The mechanism above was examined using more than dozen of melanocytes derived from donors of different ethnic backgrounds. The RNAi technology was utilized to confirm the effect of tyrosinase to induce the cytotoxicity of Rhododendrol and liquid chromatography-tandem mass spectrometry was introduced to detect Rhododendrol and its metabolites in the presence of tyrosinase. Melanocyte damage was related to tyrosinase activity at a certain threshold. Treatment with a tyrosinase-specific siRNA was shown to dramatically rescue the Rhododendrol-induced melanocyte impairment. Hydroxyl-Rhododendrol was detected only in melanocytes with higher tyrosinase activity. When an equivalent amount of hydroxyl-Rhododendrol was administered, cell viability was almost equally suppressed even in melanocytes with lower tyrosinase activity.
CONCLUSIONS:
The generation of a tyrosinase-catalyzed hydroxyl-metabolite is one of the causes for the diminishment of the melanocyte viability by Rhododendrol. | | Pigment Cell Melanoma Res. 2014 Sep;27(5):754-63. | | Rhododendrol, a depigmentation-inducing phenolic compound, exerts melanocyte cytotoxicity via a tyrosinase-dependent mechanism.[Pubmed: 24890809 ] |
METHODS AND RESULTS:
Rhododendrol, an inhibitor of melanin synthesis developed for lightening/whitening cosmetics, was recently reported to induce a depigmentary disorder principally at the sites of repeated chemical contact. Rhododendrol competitively inhibited mushroom tyrosinase and served as a good substrate, while it also showed cytotoxicity against cultured human melanocytes at high concentrations sufficient for inhibiting tyrosinase. The cytotoxicity was abolished by phenylthiourea, a chelator of the copper ions at the active site, and by specific knockdown of tyrosinase with siRNA. Hence, the cytotoxicity appeared to be triggered by the enzymatic conversion of rhododendrol to active product(s). No reactive oxygen species were detected in the treated melanocytes, but up-regulation of the CCAAT-enhancer-binding protein homologous protein gene responsible for apoptosis and/or autophagy and caspase-3 activation were found to be tyrosinase dependent.
CONCLUSIONS:
These results suggest that a tyrosinase-dependent accumulation of ER stress and/or activation of the apoptotic pathway may contribute to the melanocyte cytotoxicity. |
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