No abstract

Melanogenesis is the physiological process by which melanin is synthesized to protect the skin from UV damage. While paracrine interactions between keratinocytes and melanocytes are crucial for regulating epidermal pigmentation, the endothelin (EDN)-endothelin B-receptor (EDNRB) interaction is one of the key linkages. In this study, we found that a single exposure of normal human melanocytes (NHMs) with UVB stimulates the expression of EDNRB and its upstream transcription factor microphthalmia-associated transcription factor (MITF) at the transcriptional and translational levels. That stimulation can be abrogated by post-irradiation treatment with a French maritime pine bark extract (PBE). UVB stimulated the phosphorylation of p38 and c-jun N-terminal kinase (JNK), but not ERK, followed by the increased phosphorylation of MSK1 and CREB. The post-irradiation treatment with PBE did not affect the increased phosphorylation of p38 and JNK, but distinctly abrogated the phosphorylation of MSK1 and CREB. Post-irradiation treatment with the MSK1 inhibitor H89 significantly down-regulated the increased gene expression of MITF and EDNRB in UVB-exposed NHMs. Our findings indicate for the first time that the increased expression of MITF that leads to the up-regulation of melanocyte-specific proteins in UVB-exposed NHMs is mediated via activation of the p38/MSK1/CREB pathway but not the ERK/RSK/CREB pathway. The mode of action by PBE demonstrates that interrupting MSK1 activation is a new target for antioxidants including PBE which can serve as anti-pigmenting agents in a reactive oxygen species-depletion-independent manner.

Koji, which is used for manufacturing Japanese traditional fermented foods, has long been safely used as a cosmetic product. Although its cosmetic effect has been empirically established, the underlying mechanism has not been reported. We and other groups have previously elucidated that koji contains glycosylceramides, including N-2′-hydroxyoctadecanoyl-1-O-β-d-glucosyl-9-methyl-4,8-sphingadienine and N-2′-hydroxyoctadecanoyl-1-O-β-d-galactosyl-9-methyl-4,8-sphingadienine. This led us to hypothesise that koji exerts its cosmetic effect by acting on the keratinocytes through glycosylceramides on the gene level. Therefore, in this study, we investigated the effects of glycosylceramides from various sources on gene expression in normal human epidermal keratinocytes. The results revealed that glycosylceramides purified from white koji and the white koji-producing non-pathogenic fungus Aspergillus luchuensis and A. oryzae increased the expression of occludin (OCLN, an epidermal tight junction protein) and ATP-binding cassette sub-family A member 12 (ABCA12, a cellular membrane transporter), albeit the effect was modest relative to that of ceramides. Indeed, ceramide was increased in the keratinocytes upon koji lipid extract addition. These results indicate that glycosylceramides, which are the major sphingolipids of most natural materials, have an effect of increasing ABCA12 and OCLN expression, and suggest that koji exerts its cosmetic effect by increasing ceramide and tight junctions via glycosylceramides.

Koji, rice fermented with Aspergillus, is used for saccharification of starch contained in crops during the manufacturing of many of Japanese traditional foods and drinks. Japanese people have long eaten koji, and many beneficial substances have been reported to be contained in koji. However, there has been no report on the existence or content of galactosylceramide in koji. To address this issue, we analyzed the chemical composition of the sugar moiety of monohexosylceramide contained in koji, and elucidate that 30.3% of yellow koji is galactosylceramide, 69.7% of that is glucosylceramide, 19.2% of white koji is galactosylceramide, and 80.8% of that is glucosylceramide. This is the first report of the existence and content of galactosylceramide in koji.

Five new acyl secoiridoid glucosides along with three known secoiridoid glucosides, swertiamarin, 2'-O-acetylswertiamarin, and amarogentin, were isolated from the aerial parts of Swertia mileensis. The structures of these compounds were determined to be 2'-O-acetyl-4'-O-trans-feruloylswertiamarin, 2'-O-acetyl-4'-O-cis-feruloylswertiamarin, 2'-O-acetyl-4'-O-trans-p-coumaroylswertiamarin, 2'-O-acetyl-4'-O-cis-p-coumaroylswertiamarin, and 4'-O-trans-p-coumaroylswertiamarin from spectroscopic evidence.