4,4′-Dihydroxybiphenyl as a New Potent Tyrosinase Inhibitor

Abstract

Tyrosinase (monophenol, dihydroxy-L-phenylalanin: oxygen oxidoreductase, EC 1.14.18.1) is a copper-dependent protein widely distributed in nature.2) The enzyme catalyzes two different reactions: the hydroxylation of monophenols to o-diphenols (monophenolase activity) and the oxidation of odiphenols to o-quinones (diphenolase activity), both utilizing molecular oxygen.3)The enzymatic browning of fruits and vegetables is mostly related to the oxidation of endogenous phenolic containing compounds catalyzed by polyphenol oxidase. 4) Tyrosinase also is responsible for melanization in animals, and is the key enzyme for the regulation of melanogenesis in mammals. 5)Melanin is synthesized in epidermal melanocytes, and then is transferred into epidermal keratinocytes via the melanocytes' dendrites. 6) Melanogenesis is the process by which melanin is produced (and subsequently distributed) by melanocytes within the skin and hair follicles.7) This process results in the synthesis of melanin pigments, which plays a protective role against skin photocarsinogenesis.8) The main physiological stimulus of melanogenesis is the ultraviolet radiation of solar light, which can act directly on melanocytes or indirectly through the release of keratinocyte-derived factors such as MSH (a-melanocyte stimulating hormone). 9)One of the biggest causative agents of hyperpigmentaion is probably UV light. 10) However, skin darkening can be suppressed, at least partially, by deactivating of tyrosinase. 11)Therefore, tyrosinase inhibitors have become increasingly important in the cosmetic and medicinal products used in the prevention of hyperpigmentaion.12) Many compounds, such as hydroquinone, 13) kojic acid, 14) and benzaldehyde-O-alkyloximes 15) have been reported as tyrosinase inhibitors. The established murine B16F10 melanoma cell (B16 cells) line offers a model system with readily quantifiable markers that are characteristic of differentiating, including melanogenesis. 16) In B16 cells, a-tocopheryl ferulate was shown to have depigmenting effect. 17) Although 4,4Ј-dihydroxybiphenyl (44Ј-BP), a bisphenol derivative was known as a radical scavenger for methacrylate polymerization, 18) but its efficacy on tyrosinase inhibition and melanin biosynthesis has not been reported.The aim of this study was to characterize inhibition mode of 44Ј-BP on mushroom tyrosinase. We also examined the inhibitory effect of 44Ј-BP on melanin biosynthesis, and cell viability in B16 cells as a biomarker for the potential cytotoxicity. Cell Culture B16 cells (from Korean Cell Line Bank) were cultured in DMEM with 10% fetal bovine serum (FBS; Gibco) and penicillin/streptomycin (100 IU/50 mg/ml) in a humidified atmosphere containing 5% CO 2 in air at 37°C. B16 cells were cultured in 24-well plates for the melanin quantification and enzyme activity assays. MATERIALS AND METHODS MaterialsDetermination of 44-BP for Cell Viability The cell proliferation assay was carried out by the method of Tada et al. using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (...

Antimelanogenic Activity of 3,4-Dihydroxyacetophenone: Inhibition of Tyrosinase and MITF

“…3) Recently, another transcription factor, microphthalmia transcription factor (MITF), was shown to play a key role in melanocyte survival, development and differentiation. 2) In recent papers, we reported that 4,4 0 -dihydroxybiphenyl has a strong tyrosinase inhibitory effect that down-regulates melanogenesis, 4) and that protocatechuic aldehyde has a potent tyrosinase inhibitory effect. 5) The present work was designed to investigate the mode of inhibitory action of 3,4-dihydroxyacetophenone (3,4-DHAP) on mushroom tyrosinase activity and on tyrosinase activity and melanin content in B16 melanoma cells.…”

Inhibitory Effects of Bakuchiol, Bavachin, and Isobavachalcone Isolated fromPiper longumon Melanin Production in B16 Mouse Melanoma Cells

“…1) However, excessive melanin formation and accumulation of melanin in the skin causes hyperpigmentation skin disorders such as melasma, freckles, and geriatric pigment spots. 2,3) In mammals, -melanocyte-stimulating hormone (-MSH) is required for the development of pigmentation. Notably, -MSH binds to its specific melanocortin-1 receptor (MC1R) and increases cyclic AMP (cAMP), which induces melanogenesis by strongly up-regulating the expression of melanogenic enzymes such as tyrosinase.…”

Peptides-derived from Scales of Branchiostegus japonicus Inhibit Ultraviolet B-induced Oxidative Damage and Photo-aging in Skin Cells

“…따라서 L-tyrosine-tyrosinase 과정에 의해 생 성되는 melanin은 피부 산화적 스트레스를 유도할 수 있다 [26]. Melanin은 피부색이나 눈동자, 머리카락 등의 색을 결정 하는 색소로써 UVB 노출에 의한 세포의 손상을 억제하는 기 능을 하지만, 과도한 UVB의 노출은 과도한 melanin의 생성으 로 기미, 주근깨, 검버섯, 흑색종 등의 질병의 원인이 된다 [3,13]. 이러한 melanin의 생합성 과정에 중요한 역할을 하는 tyrosinase는 melanin 합성 과정에서 tyrosine이 dihydroxyphenylalanine (DOPA)로 변환시키고 다시 DOPA를 DOPA quinone으로 변환시키는데 작용하여 최종적으로 melanin을 합성한다 [4,9].…”