Melatonin is a lipophilic peptide hormone normally secreted by the pineal gland that plays a role in hair growth, immunoregulation, and aging, among other functions. Melanin is also synthesized and metabolized in various human skin cells, which commonly express melatonin receptor 1. As a free radical scavenger of H2O2, OH, and superoxide, melatonin improves the survival of fibroblasts irradiated by UVB and ionizing light. Melatonin also upregulates the expression of the Nrf2 transcription factor in UV-irradiated human keratinocytes, which stimulates production of antioxidant enzymes such as superoxide dismutase.

There has been tremendous recent research on the biology of melatonin in human skin cells. Metabolites of melatonin in human skin cells including fibroblasts, keratinocytes, and melanocytes results in regulating the proliferation of keratinocytes in vitro. Keratin-14 is a marker of undifferentiated keratinocytes while keratin-10 localizes keratinocytes differentiating into the stratum spinosum and granulosum. By increasing the expression of keratin-10 and keratin-14 in the epidermis, melatonin plays a role in constructing and strengthening the epidermal barrier. In addition, melatonin prevents UV related apoptosis in keratinocytes. Upregulation of heat shock protein 70 (HSP70) is a marker for keratinocyte exposure to UV radiation. Melatonin prevents an increase in HSP70 expression as a result of UV light exposure.91 Melatonin has also been shown to attenuate UVA-induced cell changes in dermal fibroblasts in vitro. Melatonin prevented the UVA related change in ECP production and induction of heme oxygenase. Importantly, melatonin downregulates collagenases such as MMP-1, MMP-3, and MMP-10. One clinical trial included 20 patients who were treated with 0.5% topical melatonin at different times before or after UV exposure. In this study, melatonin only suppressed skin erythema if it was applied before UV exposure. In other studies, melatonin has been shown to suppress skin erythema after UV light exposure. Compared to vitamin C and trolox, melanin is a more powerful antioxidant.

It has been shown that exogenous melatonin is more beneficial if applied topically rather than taken orally due to the first-pass effect of the liver. Due to its lipophilic structure, melatonin can gather in a depot on the stratum corneum. The effect of melatonin-loaded emulsions on skin was recently investigated in vivo. A Franz diffusion model showed that the emulsions could have a Kp as high as 1.13 × 10?3 cm/ hr. Two-step release patterns of the drug were observed, where 80% of the melatonin was released in the first two hours, followed by a slower phase of release. Retention of melatonin in the skin after 12 months was also demonstrated. The emulsion’s antioxidant activity remained after a storage period of 12 months. This cosmeceutical’s photoprotective effect was also demonstrated in vivo. Compared to control, the melatonin emulsions prevented structural abnormalities in the epidermis and lowered the rate of transepidermal water loss. Moreover, all emulsions tested are not irritating to skin.