By identification of the chronic inflammations that can accelerate pigmentation, lightening and brightening ingredients can be utilized within a global anti-aging approach. The cumulative anti-aging benefits are visually perceived and recognized by an even tone and color effect, improvement of photo-aging marks, control of hyperpigmentation, and healthy luminosity.

Inhibiting Melanin Synthesis
The stimulated melanogenesis cascade is a domino reaction primarily influenced by environmental factors, such as ultraviolet radiation. Appropriate ingredient combinations need to be combined to form a multi-prong attack at modulating the upstream pathway and providing safety nets at various locations further in the pathway, leading to a visible cumulative effect.

Nitric Oxide
Sandream’s raspberry ketone glucoside is an effective scavenger of nitric oxide. With the capture of the nitric oxide within the skin cell, the ingredient effectively inhibits the formation of melanin and lipid peroxidation. In vitro and in vivo clinical testing was conducted with positive effects demonstrated for skin lightening.
Natural Solution’s ingredient is from the sprout of perilla frutescens. Within a specialized cultivation process with the phytochemical rosmarinic acid as its main active constituent, nitric oxide is inhibited. In vitro testing demonstrated the inhibition activity of nitric oxide, decreased tyrosinase expression and activity, and decreased melanin transfer.

Alpha-Melanocyte-Stimulating Hormone
Alpha-melanocyte-stimulating hormone (α-MSH) is another primary step towards blocking melanin synthesis. Two companies have marketed biomimetic peptides to mediate skin pigmentation by targeting the α-MSH pathway.
Hexapeptide-2 and nonapeptide-5 act specifically as antagonists to the α-MSH receptor. By competing and occupying the α-MSH receptors, hyperproduction of melanin is opposed. Both companies substantiate the peptide ingredients with clinical testing that demonstrates a decrease of the melanin content in epidermal cells, a reduction of melanin synthesis, brightened skin, and an evened-out skin tone.

Tyrosinase Mediated
There are common, key melonagenesis activities that inhibit tyrosinase synthesis. A wide array of ingredients that can moderate this rate-limited pathway include N-acetylglucosamine, licorice extract, arbutin, vitamin C, emblica extract, lignin peroxidase, and glutathione.
A spin on the plant stem-cell technology of licorice extract is the Lonza Group’s Glycyrrhiza glabra (licorice) root callus culture extract. The technology potentiates the plant stem culture with the addition of an elicitor, added to provoke expression of key secondary metabolites. While the extract consists of a water-based and oil-based liquid medium, the ingredient is clinically-proven with in vivo and in vitro testing. Testing has demonstrated lightening and blending of the pigmentation of large blemishes with improvement in overall skin tone, yielding a lighter and more balanced skin tone.
Ascorbic acid is a naturally-occurring antioxidant that interacts with copper ion-inhibiting tyrosinase. Use is limited due to instability within hydrous cosmetic formulations. K3 has introduced aminopropyl ascorbyl phosphate, a patented, water soluble, and conjugated ascorbic acid. This ingredient is capable of penetrating the skin, is clinically-proven to be effective at melanogenesis inhibition, and is stable within a wide array of formulations. Aminopropyl ascorbyl phosphate is effective at reducing hyperpigmentation and age spots, improving skin tone, and providing other anti-aging benefits.
Active Concept’s saccharomyces/grape ferment extract is an ingredient with a patent-pending mechanism of action via histamine 3 receptor antagonism. In vitro testing proposed a repressed transcription of melanogenic genes. Clinical in vivo testing produced visible lightening results and depigmentation effects in 14 days. Additionally, a reduction in the appearance of dark spots and other hyperpigmentation on the hands, face, and décolleté, without irritation, was observed.
Gattfosse’s combination ingredient of actinidia chinensis (kiwi) fruit water and sophora flavescens root extract performs via the epidermal and dermal causes of hyperpigmentation. Clinical efficacy demonstrated that it reduced the number and the appearance of age spots while lightening the skin tone through anti-tyrosinase activity. Additionally the ingredient enhances desquamation, elimination-accumulated melanin from the upper skin layers.
Air Product’s cellular active ingredient for skin whitening and skin depigmentation launched with in vitro, in vivo, and ex vivo testing. After 14 days, the ingredient resulted in the reduction of melanin content in the stratum spinosum by 95.5 percent. In addition, the ingredient also helps promote a reduction of intracellular and extracellular melanin content.

Transfer and Distribution of Melanin
As melanin spreads through the melanocytes, the melanosome structure has multiple layers where melanin pigment can be deposited. Most ingredients that modulate the distribution, migration, and transfer of melanin also have other functions within melanogenesis. These ingredients can often be utilized as primary and secondary safety nets in the melanogenesis cascade.
Niacinamide is a key ingredient for inhibiting the transfer of the melanosomes to surrounding keratinocytes. Results from a significant number of published studies with niacinamide show that a wide array of dose-dependent claims can be achieved.
Ethyl linoleate is another ingredient that has been under examination in the medical field for inhibition of melanogenesis. Studies have demonstrated a statistically-significant reduction in pigmentation via multiple pathways of melanogenesis and the inhibition of melanin distribution.
SEPPIC’s algae extract and undaria pinnatifida extract is clinically-proven to reduce the expression of several genes, enzymes, and proteins. Not only are they involved in the reduction of melanosomes synthesis and melanosome transport, but migration of melanocytes to keratinocytes and absorption of melanosomes by keratinocytes is also reduced. In vivo clinical studies show a significant lightening effect for the global panel, including Asian and Caucasian panels.
CLR’s bellis perennis (daisy) flower extract is effectively substantiated with in vitro studies, demonstrating the reduction of endothelin expression, α-MSH binding capacity on the MC-1 receptor, melanosome transfer, and melanin formation. In vivo clinical studies concluded a significant lightening effect and reduced color intensity of age spots.
Rahn’s ingredient blend is a composition of olea europaea (olive) leaf extract, ascorbyl glucoside, and zinc PCA and works by inhibiting the formation of melanin and protein aggregates. Oleuropein, found in olive leaves, activates the proteasome to prevent the formation of the age pigment lipofuscin. The composition promotes depigmentation and prevents repigmentation of age spots. Claims are substantiated with in vitro and in vivo testing.
BioTech Marine offers an ingredient that is a stem cell culture extract of sea fennel. The ingredient, crithmum maritimum callus culture filtrate, helps inhibit all major steps of melanogenesis and reduces the capture of melanosomes by keratinocytes. Clinical evaluations have demonstrated skin that is smoother, more radiant, and has a more even skin tone.
BASF introduced a water soluble hydroxyphenoxy propionic acid that acts by inhibiting the release of melanin by the melanocytes. In vivo clinical studies, lasting 14 days, found that the ingredient reduced age spots and that the contrast between age spots and spotless areas was reduced, giving visibly-even, radiant, and brighter skin.

By influencing the original falling domino, inhibiting the cumulative effect of melanin, or providing indirect brightening mechanisms, a global anti-aging regimen that includes skin-brightening and lightening ingredients can provide comprehensive and visible anti-aging benefits.

References:
Panich, U., Tangsupa-a-nan, V., Onkoksoong, T., et al. (2011). Inhibition of UVA-mediated melanogenesis by ascorbic acid through modulation of antioxidant defense and nitric oxide system. Archives of Pharmaceutical Research, 34(5), 811-20.
Chaudhuri, R.K. (2010). Effective Skin Lightening with Protective Properties. Personal Care Magazine, 30-44.
Ando, H., Ryu, A., Hashimoto, A., Oka, M., Ichihashi, M. (1998). Linoleic acid lightens skin by accelerating proteolytic degradation of tyrosinase. Archives of Dermatological Research, 290(7), 375-81.
Herndon, J.H. Jr., Makino, E.T., Stephens, T.J., Mehta, R.C. (2014). Hydroquinone-free Skin Brightener System for the Treatment of Moderate-to-Severe Facial Hyperpigmentation. Journal of Clinical and Aesthetic Dermatology, 7(5), 27-31.
Makino, E.T., Mehta, R.C., Banga, A., Jain, P., Sigler, M.L., Sonti, S. (2013). Evaluation of a hydroquinone-free skin brightening product using in vitro inhibition of melanogenesis and clinical reduction of ultraviolet-induced hyperpigmentation. Journal of Drugs in Dermatology, 12(3), 16-20.
Navarrete-Solis, J., Castanedo-Cazares, J.P., Torres-Alvarez, B., … Moncada, B. (2011). A double-blind, randomized clinical trial of niacinamide 4% versus hydroquinone 4% in the treatment of melasma. Dermatology Research and Practice.

Diahne Patnode, expert cosmetic chemist, has over 25 years of progressive experience in formulating and developing trendsetting cosmetic products for some of the most recognized names in the industry, including Redken Laboratories, philosophy/BioMedic, and Arbonne International. After studying biochemistry at the University of Arizona, Patnode discovered the beauty industry and an insatiable curiosity for discovering the latest technological advances to create cutting-edge prestige products. She holds multiple patents and as a leader in research and product development, she continues to provide insight that delivers market leading products.