arbutin and Skin-Neoplasms

We have designed and synthesized twenty-six N-arylindazole-3-carboxamide (3a-p) and N-benzoylindazole (6a-j) derivatives to discover with excellent inhibition activities of α-MSH-stimulated melanogenesis. In the bio evaluation studies of these compounds, we discovered eighteen compounds, out of twenty-six exhibited more potent inhibition than the positive control arbutin. From the SAR studies, we identified 3k and 6g as lead compounds which displayed almost 5 and 9 times more potent inhibition of α-MSH-stimulated melanogenesis respectively than the reference arbutin. It is also evident the presence of electron withdrawing group at para position (R

Topics: alpha-MSH; Animals; Antineoplastic Agents; Cell Line, Tumor; Dose-Response Relationship, Drug; Indazoles; Melanoma, Experimental; Mice; Molecular Structure; Skin Neoplasms; Structure-Activity Relationship

From the 1-BuOH-soluble fraction of a MeOH extract of the leaves of Grevillea robusta, new arbutin derivatives and related compounds, named grevillosides J-Q (1-8), together with eight known compounds (9-18) were isolated. Various kind of acyl groups were attached to β-D-glucose at the 6-position through an ester linkage. Their structures were mainly elucidated from one- and two-dimensional NMR spectroscopic data. For exploitation as skin-lightening and anti-chloasma agents, the inhibitory activities of the isolated compounds as well as ones isolated in previous experiments (19-31) toward tyrosinase and melanin-producing B16 cells were assayed. Several compounds showed promising activity.

Topics: Animals; Arbutin; Drug Evaluation, Preclinical; Enzyme Inhibitors; Inhibitory Concentration 50; Magnetic Resonance Spectroscopy; Melanoma, Experimental; Mice; Molecular Structure; Monophenol Monooxygenase; Plant Leaves; Proteaceae; Skin Lightening Preparations; Skin Neoplasms

The compounds present in rose hips exerting an inhibitory action against melanogenesis in B16 mouse melanoma cells were investigated by dividing an aqueous extract of rose hips (RE) into four fractions. The 50% ethanol eluate from a DIAION HP-20 column significantly reduced the production of melanin and was mainly composed of procyanidin glycosides. We also found that this 50% ethanol eluate reduced the intracellular tyrosinase activity and also had a direct inhibitory effect on tyrosinase obtained as a protein mixture from the melanoma cell lysate. We also investigated the effect of orally administering RE on skin pigmentation in brown guinea pigs, and found that the pigmentation was inhibited together with the tyrosinase activity in the skin. These data collectively suggest that proanthocyanidins from RE inhibited melanogenesis in mouse melanoma cells and guinea pig skin, and could be useful as a skin-whitening agent when taken orally.

Topics: Administration, Oral; Animals; Arbutin; Cell Line, Tumor; Cell Survival; Chromatography, High Pressure Liquid; Ethanol; Female; Glycosides; Guinea Pigs; Melanins; Melanoma, Experimental; Mice; Monophenol Monooxygenase; Plant Extracts; Proanthocyanidins; Rosa; Skin; Skin Neoplasms; Skin Pigmentation; Ultraviolet Rays

Sulforaphane is a compound widely present in consumed vegetables, particularly broccoli. Previous studies have demonstrated that sulforaphane has many physiological effects including anti-cancer, anti-oxidation, and detoxification. In this study, we found that sulforaphane inhibited melanogenesis and tyrosinase expression. The inhibitory effect of 5 microM sulforaphane on melanogenesis was determined to be equivalent to that of 100 microM arbutin. In addition, sulforaphane induced phosphorylated extracellular signal-regulated kinase (ERK) and inhibited phosphorylated p38. It has been reported that the phosphorylated mitogen-activated protein (MAP) kinase family (ERK and p38) controls tyrosinase expression. Our data indicate that sulforaphane inhibited melanogenesis and tyrosinase expression by affecting the phosphorylated MAP kinase family. These findings indicate that sulforaphane might be an effective skin-whitening agent.

Topics: Animals; Arbutin; Extracellular Signal-Regulated MAP Kinases; Gene Expression Regulation; Isothiocyanates; Melanins; Melanoma, Experimental; Mice; Monophenol Monooxygenase; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Skin Neoplasms; Skin Pigmentation; Sulfoxides; Thiocyanates

Epidermal melanocytes synthesize melanin pigments and transfer them to keratinocytes, which is responsible for skin pigmentation. However, abnormal accumulation of melanin pigments causes hyperpigmentation disorders, which are substantially improved with treatment of tyrosinase inhibitor. In our ongoing study, Torilis japonica DC. (Umbelliferae) was found to inhibit melanin production. A goal of this study is to elucidate the hypopigmenting principle of T. japonica. A sesquiterpene structure of torilin was isolated from the plant extracts via bioassay-guided phytochemical analysis. Torilin dose-dependently inhibited melanin production, with an IC(50) value of 25 microM, in alpha-melanocyte stimulating hormone (alpha-MSH)-activated B16 melanoma cells. Arbutin, a positive control of skin whitener, also inhibited alpha-MSH-induced melanin production with an IC(50) value of 170 microM. As to the mode of action, torilin downregulated alpha-MSH-induced protein levels of tyrosinase without directly inhibiting catalytic activity of the enzyme. Taken together, this study shows that torilin contributes to the hypopigmenting principle of T. japonica, and suggests its pharmacological potential in melanin-associated hyperpigmentation disorders.

Topics: alpha-MSH; Animals; Apiaceae; Arbutin; Dermatologic Agents; Dose-Response Relationship, Drug; Down-Regulation; Fruit; Hyperpigmentation; Inhibitory Concentration 50; Melanins; Melanoma, Experimental; Mice; Monophenol Monooxygenase; Phytotherapy; Plant Extracts; Sesquiterpenes, Guaiane; Skin; Skin Neoplasms; Skin Pigmentation

Transesterification of arbutin and undecylenic acid vinyl ester was catalyzed by alkaline protease, Bioprase, in dimethylformamide to get arbutin derivative having undecylenic acid at 6-position of glucose moiety, 6-O-undecylenoyl p-hydroxyphenyl beta-D-glucopyranoside. The reaction rate increased with increase of arbutin concentration, and when its concentration was 0.9 M, the conversion rate was more than 90% under addition of 2 M undecylenic acid vinyl ester. The obtained arbutin ester significantly suppressed melanin production in murine B16 melanoma cells.

Topics: Animals; Arbutin; Bacterial Proteins; Cell Line, Tumor; Endopeptidases; Esters; Melanins; Melanoma, Experimental; Mice; Skin Neoplasms; Undecylenic Acids

Although arbutin is a natural product and widely used as an ingredient in skin care products, its effect on the gene expression level of human skin with malignant melanoma cells is rarely reported. We aim to investigate the genotoxic effect of arbutin on the differential gene expression profiling in A375 human malignant melanoma cells through its effect on tumorigenesis and related side-effect. The DNA microarray analysis provided the differential gene expression pattern of arbutin-treated A375 cells with the significant changes of 324 differentially expressed genes, containing 88 up-regulated genes and 236 down-regulated genes. The gene ontology of differentially expressed genes was classified as belonging to cellular component, molecular function and biological process. In addition, four down-regulated genes of AKT1, CLECSF7, FGFR3, and LRP6 served as candidate genes and correlated to suppress the biological processes in the cell cycle of cancer progression and in the downstream signaling pathways of malignancy of melanocytic tumorigenesis.

Topics: Arbutin; Cell Line, Tumor; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Melanoma; Oligonucleotide Array Sequence Analysis; Skin Neoplasms; Toxicogenetics