title: Deoxyarbutin Possesses a Potent Skin-Lightening Capacity with No Discernible Cytotoxicity against Melanosomes.
abstract: Safe and effective ingredients capable of removing undesired hyperpigmentation from facial skin are urgently needed for both pharmaceutical and cosmetic purposes. Deoxyarbutin (4-[(tetrahydro-2H-pyran-2-yl) oxy] phenol, D-Arb) is a glucoside derivative of hydroquinone. Here, we investigated the toxicity and efficacy of D-Arb at the sub-cellular level (directly on melanosomes) and skin pigmentation using in vivo and in vitro models to compare with its parent compound hydroquinone (1,4-benzenediol, HQ). At first, we examined the ultrastructural changes of melanosomes in hyperpigmented guinea pig skin induced by 308-nm monochromatic excimer lightand/or treated with HQ and D-Arb using transmission electron microscopy. The results showed that prominent changes in the melanosomal membrane, such as bulb-like structure and even complete rupture of the outer membranes, were found in the skin after topical application of 5% HQ for 10 days. These changes were barely observed in the skin treated with D-Arb. To further clarify whether membrane toxicity of HQ was a direct result of the compound treatment, we also examinedultrastructural changes of individual melanosomes purified from MNT1 human melanoma cells. Similar observations were obtained from the naked melanosome model in vitro. Finally, we determined the effects of melanosomal fractions exposed to HQ or D-Arb on hydroxyl radical generation in the Fenton reaction utilizing an electron spin resonance assay. D-Arb-treated melanosomesexhibit a moderate hydroxyl radical-scavenging activity, whereas HQ-treated melanosomessignificantly generate more hydroxyl free radicals. This study suggests that D-Arb possesses a potent ability in skin lightening and antioxidation with less melanosome cytotoxicity.
authors: Department of Dermatology, Renmin Hospital of Wuhan University, Wuhan, China.
authors: Fang
authors: http://orcid.org/0000-0003-2006-3781
authors: F
authors: Miao
authors: Department of Dermatology, Renmin Hospital of Wuhan University, Wuhan, China.
authors: Ying
authors: Y
authors: Shi
authors: Department of Dermatology, Renmin Hospital of Wuhan University, Wuhan, China.
authors: Zhi-Feng
authors: ZF
authors: Fan
authors: Department of Dermatology, Renmin Hospital of Wuhan University, Wuhan, China.
authors: Shan
authors: S
authors: Jiang
authors: Department of Dermatology, Renmin Hospital of Wuhan University, Wuhan, China.
authors: Shi-Zheng
authors: SZ
authors: Xu
authors: Department of Dermatology, Renmin Hospital of Wuhan University, Wuhan, China.
authors: Tie-Chi
authors: TC
authors: Lei
mesh_terms: D000818:Animals; D001104:Arbutin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004578:Electron Spin Resonance Spectroscopy; D006168:Guinea Pigs; D020460:Melanosomes / Q000187:drug effects* / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D012867:Skin / Q000187:drug effects* / Q000648:ultrastructure; D062327:Skin Lightening Preparations / Q000494:pharmacology*; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D062327:Skin Lightening Preparations; D001104:Arbutin; C504954:deoxyarbutin