Abstract:
BACKGROUND:Kojic acid is a fungal metabolite widely used in medicinal and cosmetic formulations as a skin-lightening agent based on its de-pigmenting activity. Although in human clinical studies kojic acid has been shown to be effective in the treatment of hyper-pigmentation disorders such as melasma, the reasons for its apparent lack of anti-melanogenic activity in cultured mammalian melanocytes are unclear. OBJECTIVES:This study was aimed to elucidate pharmacological mechanisms of the in vivo anti-melanogenic activity of kojic acid in human skin. METHODS:A primary human melanocyte and keratinocyte co-culture system was used to evaluate whether kojic-acid-induced changes in keratinocytes were associated with anti-melanogenic activities in melanocytes. The cytokine secretion profiles in response to kojic acid were analyzed. RESULTS:Kojic acid increased interleukin (IL)-6 and IL-8 production in melanocyte/keratinocyte co-cultures; however, IL-6 directly inhibited melanogenesis whereas IL-8 did not. In melanocyte monocultures, kojic acid did not increase IL-6 production whereas in keratinocyte monocultures it significantly up-regulated IL-6 gene and protein expression. Therefore, the up-regulation of IL-6 in melanocyte/keratinocyte co-cultures seems to be originated from kojic acid-induced changes in keratinocytes. Anti-IL-6 antibody treatment antagonized the anti-melanogenic effect of kojic acid on the co-cultures. CONCLUSIONS:The pharmacological mechanism of kojic acid to explain clinically effective anti-melanogenic activity on hyper-pigmented skin is associated with the kojic acid-induced IL-6 production in keratinocytes. The cross-talk between melanocytes and keratinocytes should be determined in future studies on the pharmacological mechanisms of clinically effective dermatological drugs acting on the epidermis.
journal_name
J Dermatol Scijournal_title
Journal of dermatological scienceauthors
Choi H,Kim K,Han J,Choi H,Jin SH,Lee EK,Shin DW,Lee TR,Lee AY,Noh Mdoi
10.1016/j.jdermsci.2012.03.002subject
Has Abstractpub_date
2012-06-01 00:00:00pages
207-15issue
3eissn
0923-1811issn
1873-569Xpii
S0923-1811(12)00099-0journal_volume
66pub_type
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