Effects of a Standardized Hydrogenated Extract of Curcumin (Curowhite™) on Melanogenesis: A Pilot Study

Abstract

The stimulation of melanogenesis by novel natural products is desirable for cosmetic applications such as skin tanning, anti-greying, and clinical use for treating vitiligo and leukoderma disorders. Microphthalmia transcription factor (MITF) is a central transcription factor that controls the expression of tyrosinase, which is a key enzyme responsible for catalyzing the rate-limiting processes of melanin production. Tetrahydrocurcuminoids (THCr), which mostly consist of tetrahydrocurcumin (THC), are a colorless bioactive mixture derived from curcuminoids that are extracted from the Curcuma longa plant. THCr has been reported to exhibit superior properties, including antioxidant and anti-inflammatory effects. Our previous study reported the greater melanogenesis-stimulating effects of purified THC, compared to hexahydrocurcumin (HHC) or octahydrocurcumin (OHC). Curowhite™ (CW) is a proprietary extract that consists of 25% hydrogenated curcuminoids (mixture of THCr, hexahydrocurcuminoids, and octahydrocurcuminoids) encapsulated in a β-cyclodextrin (βCyD) excipient. The encapsulation of THCr in a suitable excipient, such as the widely popular cyclodextrins, helps to enhance the stability, solubility, and bioavailability of the THCr. CW is marketed as a nutraceutical with GRAS status and is safe when administered orally, as shown in vivo studies. However, the impact of CW on melanogenesis remains unexplored. Herein, the impact of CW on melanogenesis were investigated using B16F10 and MNT-1 cells. Our findings show that CW is markedly cytotoxic to B16F10 cells without affecting the cellular melanin content. However, in MNT-1 cells, CW significantly stimulated intracellular melanin content over the concentration range (20–60 µg/mL) with increased dendrite formation while being nontoxic to MNT-1 cells or HaCaT cells after a 5-day treatment. Examination of the effects of the excipient βCyD on cytotoxicity and melanogenesis confirmed that the excipient had no contribution to the biological impacts that were found to be exclusively attributable to the encapsulated mixture (THCr). The mechanisms of CW’s promelanogenic effects in MNT-1 cells were found to be related, at least in part, to an increase in tyrosinase and MITF protein levels, as CW did not alter tyrosinase activity in MNT-1 cells. Moreover, CW exhibited antioxidant activity as obtained through DPPH radical scavenging assay. Together, the findings of this pilot study indicate that CW might hold an exciting avenue as a pro-pigmenting nutraceutical for treating hypopigmentation disorders, the detailed mechanisms of which warrant further exploration. Moreover, future investigations are necessary to examine CW’s effects on melanogenesis in normal human melanocytes and in vivo studies.