564 Melasolv, a skin lightening compound with different mechanisms to regulate skin pigmentation

Abstract

The pigmentation of human skin (nevi, senile lentigines, melasma, etc) is regulated by a complex process involving the synthesis and distribution of melanin. Overexpression of melanin is induced by the off-balance between the signals which regulates melanin synthesis, this can be caused due to a response to external or internal stimulus that often affects the genes related to melanogenesis. To date, many studies have focused on developing direct enzymatic inhibitors of tyrosinase in order to achieve a skin-lightening effect. However, it was also reported that these direct inhibitors could be converted to quinone derivatives by tyrosinase-catalyzed oxidation, which lead to undesirable outcomes. Therefore, we have studied intrinsic inhibitory factors of melanogenesis in skin with the objective to achieve a lightening effect without the undesirable potential side effects. It was reported that non-coding RNAs including H19, miR125b and WIF1 were decreased in hyper-pigmented skin such as melasma and nevi. And it was found out that melanogenesis could be inhibited by increasing these lightening genes expression in normal human epidermal melanocytes and keratinocytes. Our group showed that the 3, 4, 5-trimethoxy cinnamate thymol ester (TCTE, Melasolv®), synthesized from gallic acid, is a lightening active which decreases tyrosinase protein formation by regulating the MITF. Likewise, we have also observed that Melasolv significantly decreased melanogenesis by increasing expression of the lightening genes H19, miR125b and WIF1 in the skin cells. Finally, we have confirmed the lightening effect of Melasolv in 3D human skin equivalent. Nonetheless, since Melasolv is not a direct inhibitor of tyrosinase enzymatic activity, it is extremely unlikely that nocive quinone derivatives conversions occur. From these results, we have proposed Melasolv as an active for lightening effects with a safer profile, when considering undesirable effects, to treat pigmentary disorder and uneven skin color.