Up- or Downregulation of Melanin Synthesis Using Amino Acids, Peptides, and Their Analogs

Abstract

Harmonious synthesis and distribution of melanin in the skin contribute to the expression of beauty and the maintenance of health. When skin pigmentary disorders occur because of internal or external factors or, when there is a need to artificially increase or reduce the pigmentation level of the skin for aesthetic or therapeutic purposes, various pharmacological therapies are applied but the results are not always satisfactory. Studies have been conducted to improve the efficacy and safety of these treatment strategies. In this review, we present the latest studies regarding peptides and related compounds that may be useful in artificially increasing or reducing skin melanin levels. Certain analogs of α-melanocyte stimulating hormone (MSH) and oligopeptides with the sequences derived from the hormone were shown to promote melanin synthesis in cells and in vivo models. Various amino acids, peptides, their analogs, and their hybrid compounds with other chemical moieties were shown to inhibit tyrosinase (TYR) catalytic activity or downregulate TYR gene expression. Certain peptides were shown to inhibit melanosome biogenesis or induce autophagy, leading to decreased pigmentation. In vivo and clinical evidence are available for some compounds, including [Nle4-D-Phe7]-α-MSH, glutathione disulfide, and glycinamide hydrochloride. For many other compounds, additional studies are required to verify their efficacy and safety in vivo and in clinical trials. The accumulating information regarding pro- and antimelanogenic activity of peptides and related compounds will lead to the development of novel drugs for the treatment of skin pigmentary disorders.

Mechanistic Basis and Clinical Evidence for the Applications of Nicotinamide (Niacinamide) to Control Skin Aging and Pigmentation

“…If nicotinamide plays a role in inhibiting melanosome transfer in preventing skin pigmentation, combining it with other active ingredients that play a different role would maximize the effect. Potential candidates for combination with nicotinamide for this purpose may include substances that inhibit the expression of enzymes involved in melanin synthesis [ 149 , 150 ], that inhibit the catalytic activity of an enzyme [ 151 , 152 , 153 ], and/or that reduce the relative ratio of eumelanin to pheomelanin [ 154 , 155 ].…”

Promelanogenic Effects by an Annurca Apple-Based Natural Formulation in Human Primary Melanocytes

“… 39 They act by interference with the melanogenesis process, mostly via tyrosinase inhibition, among others. 40 , 41 Moving in this direction, here we show that a natural formulation (AMS) from Annurca Apple cultivar, autochthonous of Campania region (Southern Italy) and endowed with a special tropism for human skin, stimulates a significant promelanogenic effect in pigmented cells. Indeed, without the evidence of adverse biological responses in vitro, a significant increase in melanin cytosolic accumulation is detected when human melanocytes are incubated under controlled conditions with the nutraceutical.…”

“… 37 , 38 Consequently, disposal of skin pigmenting agents with both drug- and cosmetic-like properties is an urgent need, so that the discovery and development of melanogenesis stimulators have become a very dynamic area of research for academic and medical institutions, and cosmetic industries. 39 , 40 Several recognized melanin activators are of synthetic derivation, but many others originate from natural molecules, with plant kingdom as the main resource of compounds endowed with favourable bioactivities. 19 , 20 In this framework, the number of molecules effectively acting as melanogenesis stimulators is increasing but still limited.…”

Pharmacologic manipulation of skin pigmentation

“…Individuals with homozygous loss‐of‐function MC1R polymorphisms who tend to have red hair and poor‐tanning ability may not benefit from peptide‐induced protection from melanoma, and however, this approach could benefit MC1R heterozygous persons who number in the millions and are at increased risk of UV‐induced skin pathologies including melanoma. It is also worth noting that a tetrapeptide and tripeptide agonists are only two “lengths” of MC1R peptide agonists with demonstrated melanogenic activity; a host of oligopeptides with varying amino acid lengths have been found to manipulate melanogenesis and are worth further investigation (Boo, 2020). Abdel‐Malek and co‐workers recently published that MSH tetra‐ and tripeptide agonists highly selective for MC1R stimulated melanogenesis enhanced repair of UV damage and reduced apoptosis in human melanocytes (Koikov et al., 2021), and therefore, MSH peptide agonists are an active area in development.…”