Preclinical studies on melanogenesis proteins using a resveratrol-nanoformula as a skin whitener

A naturally occurring polyphenol called trans-resveratrol has received a lot of attention due to its possible health advantages for humans. The low solubility of trans-resveratrol and its isomerization upon UV exposure strongly limit its application as a skin-whitening agent. In the present study, to increase trans-resveratrol solubility, a new nanoformula was created by combining hydrophilic surfactants and oils. Trans-Resveratrol nanoformula has been prepared, characterized, and applied as a skin-whitening agent on the dorsal skin of Guinea pigs. The optimized trans-resveratrol nanoformula with a particle size of 63.49 nm displayed a single peak and a polydispersity index [0.36 ± 0.02]. In addition, the zeta potential of the optimized formula was -30.4 mV, confirming the high stability of this nanoformula. The melanin contents in the trans-resveratrol nanoformula-treated group were substantially lower than those of the control and the blank nanoformula-treated groups after staining of the dorsal skins [black areas] of guinea pigs with Fontana Mountain dye. The pigmentation index in the control, blank nanoformula, and optimized trans-resveratrol nanoformula were 329.4 ± 36.9, 335.8 ± 71.4, and 124.8 ± 19.6 respectively. Confirming this finding, immunohistochemistry analysis of skin tissues revealed that the expressions of melanogenesis-regulating proteins such as tyrosinase and microphthalmia-associated transcription factor were down-regulated. The safety of topical application of trans-resveratrol nanoformula was validated by no changes in free radical levels and oxidative stress markers proteins in the livers and kidneys of guinea pigs at the end of the experiment. Conclusions: A novel trans-resveratrol nanoformula as well as the mechanism whereby it promotes skin whitening effects were presented. Furthermore, the study illustrated that trans-resveratrol nanoformula is safe, non-toxic, and can be applied for skin whitening, although more research on human skin is needed.