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Background: Antimelanogenic peptides are potentially useful to treat hyperpigmentation, but many peptides have limited application because of high cost and/or low activity., Objectives: To identify small and potent peptide inhibitors of cellular melanin synthesis that are useful for cosmetic and medical applications., Methods: A positional scanning synthetic tetrapeptide combinatorial library was used for screening of potentially active peptides. Antimelanogenic activities of the peptide pools and individual peptides were evaluated in B16-F10 melanoma cells and human epidermal melanocytes treated with alpha-melanocyte-stimulating hormone (α-MSH)., Results: Predicted active tetrapeptide sequences were R-(F/L)-(C/W)-(G/R)-NH 2 . Of the individual tetrapeptides tested, D3 (RFWG-NH 2 ) and D5 (RLWG-NH 2 ) exhibited high antimelanogenic activities. Tetrapeptide D9 (FRWG-NH 2 ) with a sequence identical to that of a portion of α-MSH also showed antimelanogenic activity. Of the tripeptides tested, E5 (FWG-NH 2 ), E6 (LWG-NH 2 ) and E7 (RWG-NH 2 ) were relatively more active. Dipeptide F1 (WG-NH 2 ) and monopeptide G1 (G-NH 2 , glycinamide) retained activity, but G2 (Ac-G-NH 2 ) and G3 (glycine) did not. The antimelanogenic activities of peptides D3, E5, F1 and G1 were verified in α-MSH-stimulated human epidermal melanocytes. Commercially available G-NH 2 ·HCl suppressed the phosphorylation levels of cAMP-responsive element binding protein, protein levels of microphthalmia-associated transcription factor and tyrosinase, l-tyrosine hydroxylase activity of tyrosinase, and the melanin levels in stimulated cells., Conclusions: Small peptides, including glycinamide and tryptophanyl glycinamide, are potent antimelanogenic agents with potential value for the treatment of skin hyperpigmentation., (© 2019 British Association of Dermatologists.)

Background: Abnormal deposition of melanin may cause an aesthetic skin problem; therefore, the control of unwanted excessive melanin synthesis is the major goal of cosmetic research., Objectives: To identify novel tyrosinase (TYR) inhibitors from marine plants and examine their cellular antimelanogenic effects., Methods: The extracts of 50 marine plants endemic to Korea were screened against human TYR. Active constituents were then isolated from the selected plant extracts that showed potential and their chemical structures elucidated. Furthermore, their antimelanogenic effects were examined using murine melanoma B16/F10 cells and human epidermal melanocytes (HEM)., Results: Among the tested extracts, that of Phyllospadix iwatensis Makino exhibited the strongest human TYR inhibitory activity. The active constituents were purified from the butanol fraction of the P. iwatensis extract and identified as hispidulin 7-sulfate and luteolin 7-sulfate. Luteolin 7-sulfate inhibited human TYR more strongly than hispidulin 7-sulfate, luteolin, hispidulin and arbutin. Furthermore, luteolin 7-sulfate showed lower cytotoxicity than luteolin in both B16/F10 cells and HEM. Luteolin 7-sulfate attenuated cellular melanin synthesis more effectively in B16/F10 cells and HEM stimulated by α-melanocyte-stimulating hormone and l-tyrosine than arbutin., Conclusions: This study demonstrates that luteolin 7-sulfate isolated from P. iwatensis is a human TYR inhibitor with advantageous antimelanogenic properties, and would be useful for development as a therapeutic agent for the control of unwanted skin pigmentation., (© 2016 British Association of Dermatologists.)

Background: It has been recently recognized that p-coumaric acid (PCA) is a strong inhibitor of cellular melanogenesis., Aim: To evaluate the erythema-suppressive and skin-lightening effects of PCA after topical application to human skin., Methods: The control and PCA cream products were applied twice daily to the skin of the forearm of 21 subjects before and after ultraviolet (UV) irradiation to determine whether they could prevent erythema formation and pigmentation. The cream products were also applied to different areas only after the induction of erythema or pigmentation to determine whether they could have a depigmenting effect., Results: A 7-day application of control and PCA cream products before UV irradiation decreased UV-induced erythema formation by 31% and 77%, respectively, compared with untreated skin. When the PCA cream was applied after UV irradiation, its effects on skin colour or pigmentation were less remarkable. However, the melanin index was significantly decreased at the sites treated with PCA cream for 70 days compared with control sites, and the Individual Typology Angle (ITA°) value was increased significantly. Of the 21 subjects, 2 had mild adverse skin reactions to both the PCA and control creams., Conclusion: These results suggest that PCA cream can reduce UV-induced erythema formation and subsequent pigmentation in human skin., (© The Author(s). CED © 2010 British Association of Dermatologists.)

Background: Recent study has demonstrated that Sasa quelpaertensis (Korean name, Jeju-Joritdae) extracts inhibit cellular melanogenesis implicating potential use in the control of skin pigmentation., Objectives: The purpose of the present study was to elucidate the active constituents of this plant inhibiting melanogenesis and the associated mechanism., Methods: The effect of the plant-derived materials on melanin production and/or tyrosinase expression was examined in murine melanoma B16/F10 cells and neonatal human melanocytes., Results: When tested in melanoma B16/F10 cells treated with the alpha-melanocyte stimulating hormone (alpha-MSH), the aqueous ethanol extract of S. quelpaertensis culm inhibited the cellular melanogenesis more effectively than its leaf extract. A major active compound was isolated from the culm extract by solvent fractionation and column chromatography, and identified to be p-coumaric acid by spectroscopic and chromatographic analyses. The compound (p-coumaric acid) inhibited alpha-MSH-stimulated cellular melanogenesis more effectively than arbutin or other structurally similar compounds including 3-(4-hydroxyphenyl) propionic acid, cinnamic acid and caffeic acid. It also attenuated alpha-MSH-dependent increase of tyrosinase protein. The antimelanogenic effect of p-coumaric acid was also verified in neonatal human melanocytes., Conclusions: The present study identified p-coumaric acid as a main constituent of S. quelpaertensis inhibiting cellular melanogenesis. Because of its structural similarity, p-coumaric acid may interfere with l-tyrosine action in the control of tyrosinase expression in response to alpha-MSH.

Background: Increased production and accumulation of melanin is characteristic of a large number of skin diseases, including acquired hyperpigmentation such as melasma, postinflammatory melanoderma and solar lentigo. Thus, there is a increasing need for the development of depigmenting agents., Objectives: To evaluate the depigmenting capacity of 2,5-dimethyl-4-hydroxy-3(2H)-furanone (DMHF) and to elucidate the mechanisms by which it inhibits alpha-melanocyte-stimulating hormone (alpha-MSH)-induced melanogenesis in B16 melanoma cells in vitro., Methods: Several experiments were performed in B16 melanoma cells. We studied melanin content, tyrosinase activity and cAMP production, and performed cAMP response element (CRE) luciferase reporter assay and Western blots for proteins involved in melanogenesis., Results: The melanin content and tyrosinase activity induced by alpha-MSH were inhibited significantly by DMHF. To clarify the mechanism of the depigmenting property of DMHF, we examined the involvement of DMHF in cAMP signalling induced by alpha-MSH. In CRE luciferase reporter assay, CRE reporter activation induced by alpha-MSH was inhibited by DMHF. Additionally, although DMHF did not inhibit cAMP production by alpha-MSH, both CRE binding protein (CREB) phosphorylation and the reduction of glycogen synthase kinase-3beta phosphorylation by alpha-MSH were blocked by DMHF. These data suggest that DMHF inhibits the downstream step of cAMP production induced by alpha-MSH, consequently inhibiting melanogenesis. This suggestion was further confirmed by the fact that the increased production levels of microphthalmia-associated transcription factor, tyrosinase and tyrosinase-related protein-1 induced by alpha-MSH were all reduced by DMHF in B16 melanoma cells., Conclusions: Our study shows that DMHF inhibits alpha-MSH-induced melanogenesis by suppressing CREB phosphorylation, which is induced by protein kinase A, and suggests that DMHF may be an effective inhibitor of hyperpigmentation.