Melanogenesis: 5 key control points

Melanogenesis: 5 key control points

Melanocytes are cells that produce melanin. They have the appearance of branched cells, the body of which lies in the basal layer of the epidermis. Their appendages enter the upper spiny layers and transmit melanin, coloring the skin.

Melanoblasts are precursor cells of melanocytes in embryogenesis and are formed during gastrulation in the developing embryo at the dorsal edge of the neural crest (NC).

NC cells are highly mobile and can give rise to many cell types, including melanocytes that migrate into the basal layer of the epidermis and hair follicles.

In adults, melanocytes are long-lived dendritic cells with a slow cell cycle that do not have a significant source of stem cells.

Therefore, the process of melanogenesis is not fully understood. But we can still control it.

Melanogenesis

• Oxidative reactions from the amino acid tyrosine to DOPA-quinone through DOPA (dioxyphenylalanine) with the participation of tyrosinase
• Melanin accumulates in melanosomes and is transferred to surrounding keratinocytes
• In keratinocytes, melanosomes create a protective “umbrella” over the nucleus

Distribution of pigment in the epidermis

• The uniform distribution of the pigment provides reliable protection against UV rays.
• Transfer of melanin to basal keratinocytes by processes of the melanocyte
• The way of pinocytosis

The role of melanin in the skin

• Melanin performs not only a protective, but also an immunoregulatory role
• Transfer of acidified melanin-containing melanosomes to neighboring keratinocytes participate in acidification of the stratum corneum of pigmented skin
• Increases the barrier function of the skin and the integrity/density of the stratum corneum, and has an antimicrobial effect

Regulation of melanogenesis

• Exposure to ultraviolet light (UV) increases the rate of formation of melanosomes and the rate of their delivery to keratinocytes.
• Melanin synthesis and its transport into epithelial cells are activated by melanocyte-stimulating (MSH) and adrenocorticotropic (ACTH) hormones.

Melanocyte-stimulating hormone

Melanotropin is a peptide hormone. It has a stimulating effect on melanocytes, increasing the synthesis of pigments, causing an increase in the size and number of pigment cells. The formation of α-, β-, and γ-melanotropins is regulated by hormones of the hypothalamus production:

• increases under the influence of serotonin, thyroliberin, corticoliberin,
• decreases under the influence of dopamine, somatostatin, prolactin, neuropeptide

Adrenocorticotropic hormone (Adrenocorticotropin, ACTH) is a peptide that includes 39 amino acids.

Activates: corticoliberin, which is synthesized during stress (anxiety, fear, pain) under the influence of nerve signals from brain structures, vasopressin, angiotensin II, catecholamines

ACTH also has its own daily rhythm – the maximum concentration in the blood is reached in the morning hours, the minimum – at midnight.

Disruption of melanogenesis

Damage to melanocytes results in a disruption of melanogenesis, leading to an imbalance in skin pigmentation. If the structural proteins of melanosomes sustain damage, it disturbs the distribution of melanin. In the absence of necessary synthesis enzymes, melanin synthesis becomes inadequate. Consequently, hypo- or hyperpigmentation may occur.

Causes of melanogenesis disorders

• External factors – changes in the epidermis: UV excess; Skin traumatization
• Internal factors – changes in the dermis: Violation of microcirculation; Hormonal imbalance; Medicinal products

Hyperpigmentation due to changes in the epidermis – External factors

Hyperinsolation – an excess of UV rays:

• Activation of the melanin synthesis cascade
• Inflammatory changes in tissues (BAV, leukocyte infiltration, free radicals)

Hyperinsolation will always lead to hyperpigmentation, activation of the melanin synthesis cascade, plus inflammatory changes in tissues. We need daily protection with antioxidants, anti-inflammatory components and components that will block the synthesis of melanin.

Post-traumatic hyperpigmentation Excessive melanocyte activity (BAV, leukocyte infiltration, vascular changes) in response to mechanical, chemical, biological stimuli.

Hyperpigmentation due to changes in the dermis – Internal factors

Hormonal disorders

• endocrine pathologies
• pregnancy and lactation

Medicines

• antibacterial drugs
• hormonal drugs

A cosmetologist cannot influence internal factors. But he can draw the patient’s attention to them and recommend consulting an endocrinologist. Endocrinologists can prescribe oral contraceptives for the treatment of pathology, which in turn will change the entire hormonal background, which is also important and can lead to hyperpigmentation of the skin.

5 key points of melanogenesis control

1. Protection against UV radiation
2. MSH inhibitors
3. Tyrosinase inhibitors
4. L-DOPA inhibitors
5. Melanosome transfer inhibitors

Protection against UV radiation

Daily sun protection is necessary for everyone! The Reneo Cosmetics brand offers us a great selection:

• Sun-Block Emulsion SPF50 – has a light fluid texture, does not leave a white residue, and gives a matting effect. This cream is ideal for oily and problematic skin, it will not be felt and will also give a light matting effect.
• Cream-Protector SPF30 – has a denser texture and moisturizing effect, is more suitable for dry or normal skin prone to dryness. This cream is for those who like their skin to shine a little with a natural, healthy glow. The cream does not leave a white residue, contains additional components that moisturize the skin.

100% of patients with hyperpigmentation are prescribed daily sun protection. And in fact, we prescribe it not only for the correction of hyperpigmentation, but also for everyone as a prevention of photoageing.

Melanostimulating hormone (MSH) inhibitors

• Reduce hormone production indirectly – reduce stress
• Sedation of the nervous system – relaxing treatments, massage

Tyrosinase inhibitors

3 types of substances that regulate the work of cells are involved in melanogenesis: hormones, enzymes and amino acids.

• Ascorbyl Tetraisopalmitate
• Glycolic acid
• Azelaic acid
• Kojic acid
• Hexylresorcinol

Ascorbyl Tetraisopalmitate is the fat-soluble version of ascorbic acid (vitamin C) contains 4 molecules of palmitic acid

• Effective skin absorption
• Effectiveness of penetration into human dermal fibroblasts
• Inhibition of melanin
• Inhibition of tyrosinase activity
• Inhibition of sebum oxidation
• Neutralization of active forms of oxygen
• Stimulation of collagen synthesis
• Inhibition of the activity of collagen-destroying enzymes
• Protection of DNA from exposure to ultraviolet rays
• Fights hyperpigmentation
• Stimulates collagen synthesis and inhibits enzymes that destroy it
• Provides protection of lipids of the epidermis and cell membranes
• Prevents oxidative stress and lipid peroxidation
• Moisturizes the skin (by slowing down TEWL)

The efficiency of penetration of Ascorbyl Tetraisopalmitate (VC-IP) into human fibroblasts (NHDF) was tested by measuring the concentration of ascorbic acid 2 hours after the introduction of VC-IP. The content of ascorbic acid in the skin after the administration of VC-IP was significantly higher than after the administration of L-ascorbic acid alone. This confirms the effectiveness of VC-IP ascorbic acid release when penetrating the skin.

Glycolic acid

• Effective in the treatment of hyperpigmentation.
• As a result of clinical studies, it was established that glycolic acid in the amount of 300-500 μg/ml inhibits the formation of melanin without harming cell growth.
• Inhibits the enzyme tyrosinase.
• Provides a keratolytic effect – exfoliates colored keratinocytes in a concentration of 10% and above.
• Moisturizing effect
• Using an 8% glycolic acid solution increases the skin’s ability to absorb and retain moisture by 60-70%.
• Antioxidant and anti-inflammatory action
• Stimulation of collagen synthesis

REVIT АНА CREAM – Reactivating vitaminized cream with glycolic acid

✓ rejuvenating, restructuring dermis
✓ brightening, strengthening blood vessels
✓ keratolytic action

A cream with a dense texture

• Glycolic acid (15%)
• Vitamin C (ascorbyl tetrapalmitate)
• Vitamin E (tocopherol)

Glycolic acid + enzymes

• softening and moisturizing action.
• stimulation of cell renewal

Enzymes delicately destroy the connections between keratinocytes and allow glycolic acid, even in low concentration, to penetrate deep layers to retain moisture. RENEWING ENZYM АНА SERUM

P107 – in procedures at the 6th stage
H108 – in home care, daily at night, after skin cleansing

• Glycolic acid (5%)
• Keratoline
• Raspberry extract

Keratoline – biotechnological enzyme. Bacillus subtilis is a fermentation product and a proteolytic enzyme, the most active among proteases. It catalyzes the hydrolysis of proteins and peptides, esters and amides of N-protected amino acids, due to which the adhesion of corneocytes is weakened; daily in the evening, after cleansing the skin

Glycolic acid + Arginine

Arginine – an amino acid that has a positive charge, which becomes negative when it gets on the skin, and contributes to deeper penetration of glycolic acid into the skin. Soothes, moisturizes, accelerates skin regeneration. Glycolic acid + arginine form an amphoteric complex that has the ability to change the charge, giving or adding H+. Reduces the irritating effect of glycolic acid – it can be used even for sensitive skin Provides slow release of components

PEEL-EXPERT LIGHT

рН 3,3 Gel
Versatile, without rehabilitation, the start of a peel course for all skin types!

✓ gently smoothes the microrelief
✓ accelerates tissue regeneration
✓ fills the skin with antioxidants
✓ stimulates the compaction of the dermis
✓ moisturizes, enriching the NMF of the epidermis

• Mandelic acid 15%
• Glycolic acid 6%.
• Lactic acid 5%
• Salicylic acid 1.5%
• Arginine
• Allantoin

Azelaic acid Azelaic acid is normally formed in the human body during lipid metabolism (formed by the oxidation of linoleic acid) on the skin as a result of the vital activity of resident microorganisms

• Slows down the formation of melanosomes
• Selectively affects abnormal melanocytes
• Eliminates post-inflammatory hyperpigmentation
• Suitable even for 4-5 skin phototypes
• Contributes to the reduction of skin pigmentation due to the effect on the enzyme systems of activated melanocytes
• Inhibits tyrosinase
• Neutralizes active forms of oxygen secreted by neutrophils
• Suppresses the activity of melanocytes (inhibits NADP-D). The effectiveness of depigmentation is not inferior to 4% hydroquinone cream
• Suppresses the activity of pro-inflammatory mediators (kallikrein-5)
• Reduces the synthesis and secretion of the main pro-inflammatory cytokines (interleukins 1 and 8, tumor necrosis factor alpha) and antimicrobial peptides, blocking the activity of nuclear factor kappa B
• (nuclear factor kappa B, nf-kb)
• AK stimulates the expression of the anti-inflammatory signal molecule ppar-gamma (peroxisome proliferator-activated receptors – a receptor that activates the proliferation of peroxisomes), which
• reduces the release of cytokines and suppresses inflammation
• Has an antiandrogenic effect, inhibiting the synthesis of 5α-reductase type 1, which leads to a decrease in the content of dehydrotestosterone in sebocytes

Azelaic acid + Glycine = Роtassium azeloyl diglycinate 

Potassium azeloyl diglycinate – a biologically active complex that has the properties of azelaic acid and the glycine amino acid.

• Anti-inflammatory effect (blocks 5-alpha-reductase, inhibits the activity of sebaceous glands).
• Antioxidant action (neutralizes free radicals, prevents the formation of reactive oxygen species in neutrophils).
• Inhibits tyrosinase (reduces melanin synthesis, corrects hyperpigmentation of any genesis)
• Keratolytic action (restores normal differentiation of cells in the epidermis, evens out the microrelief).
• Glycine additionally soothes the skin, reduces redness, and moisturizes it.

Potassium azeloyl diglycinate better inhibits tyrosinase compared to β-arbutin, and the reduction was dose-dependent. 4-SYNERGY BRIGHTENING CREAM

✓ regulation of sebaceous glands.
✓ correction of hyperpigmentation
✓ mild keratolytic action
✓ light weightless texture

• Potassium Azeloyl Diglycinate is a biologically active complex that has the properties of azelaic acid and the amino acid glycine.
• Niacinamide is a powerful regulator of cellular metabolism. Increases the synthesis of ceramides and free fatty acids in the epidermis.
• Hexylresorcinol is an amphiphilic lipid, a tyrosinase blocker that ensures high bioavailability of acids.
• Allantoin has an active softening and healing effect, activates the regeneration of cells due to their proliferation.

Hexylresoncinol  Hexylresoncinol is an amphiphilic lipid, a derivative of resorcinol.

• Suppresses the processes of melanin synthesis, which ensures safe brightening and whitening of pigment spots of any origin.
• Proven: the effectiveness of hexylresorcinol is 4 times higher than the effectiveness of hydroquinone at a concentration of 4%.
• Prevents glycation processes
• It exhibits powerful antioxidant properties
• It has estrogen-like activity that stimulates the synthesis of the intercellular substance of the dermis.

Kojic acid

• Product of metabolism of fungi of the species aspergillus, aerobacter and penicillum.
• Inhibits tyrosinase
• Under its influence, melanocytes get rid of their appendages
• Eliminates active forms of oxygen
• Keratolytic effect
• Antibacterial action

The liposomal form of kojic acid has a number of advantages:

• increased bioavailability
• improved absorption
• stable form

PEEL EXPERT SHINE рН 3,0 Liquid Peels without a rehabilitation period.

✓ Intensive brightening, revitalization, lifting
✓ Antioxidant protection of cells
✓ Control of melanogenesis
✓ Powerful restoration of the hydrobalance of the skin

• Lactic acid 9%
• Kojic acid 2%
• Glutathione
• Retinol 0.25%
• 4-butylresorcinol
• A complex of fermented oils (apricot seeds, sweet almonds)
• Licorice root extract

Licorice root extract

• It has a light brightening effect: it slows down the process of the release of melanin into the upper layers of the epidermis.
• Reduces the activity of inflammatory mediators
• Has a strengthening effect on vascular walls. Reduces the fragility of blood vessels, at the same time improves blood circulation, correspondingly increases the flow of useful substances to the basal cells of the epidermis.
• Softens and soothes the skin for any irritations and inflammations, relieves itching, redness, peeling

5% ALPAFLOR® GIGAWHITE complex

• The result of a research program in which about a hundred plants were selected to determine their ability to inhibit tyrosinase.
• Dopachrome foaming was measured using a spectrophotometer
• Even greater tyrosinase inhibitory activity was found in cell cultures of 7 plants. They were active not only on whole cells (with their membranes), but also on cell lysates (the membranes were destroyed).
• It was this discovery that led to the creation of ALPAFLOR® GIGAWHITETM. The plants were combined in a patented synergistic ratio, which made it possible to maximize their activity and obtain an even more effective compound.
• In in vitro, ex vivo and in vivo tests, ALPAFLOR® GIGAWHITE affects the tyrosinase inhibition mechanism involved in biosynthesis.

BRIGHTENING ALPAFLOR SERUM – Brightening serum with antioxidant effect

✓ Correction of hyperpigmentation and anti-ageing
✓ Evens out and brightens skin tone
✓ Filling wrinkles and moisturizing the skin
✓ Anti-edematous and anti-inflammatory action

• ALPAFLOR® GIGAWHITE complex (5%) – a unique combination of 7 alpine herbs: inhibition of tyrosinase, record content of vitamin C in plant extracts, powerful antioxidant effect)
• Lecithin
• Hyaluronic acid

L-DOPA inhibitors

Hydroquinone blocks the conversion of the amino acid tyrosine to dioxyphenylalanine (DOPA) Hydroquinone has a number of side effects:

• destruction of melanocytes
• ochronosis (coloring of the skin in a yellowish or blue shade)
• carcinogenic effect

!!! All over the world, at the legislative level, the concentration of hydroquinone in cosmetic products is very limited (products with a concentration of 2-4% are prescribed by a doctor).

Melanosome transfer inhibitors

Human epidermal keratinocytes express NMDA receptor 1 (N-methyl-D-aspartate), the stimulation of which leads to an increase in the number of filopodia between melanocytes and keratinocytes
Disorganization of β-tubulin microfilaments in the intracellular cytoskeleton is associated with calcium influx
At this stage of melanogenesis, the greatest activity of oxidative reactions is noted
A detailed understanding of the process of melanosome transfer is critical to the development of treatments for hyper- and hypopigmented skin disorders.

Niacinamide Niacinamide is a water-soluble form of vitamin B3, a strong regulator of cellular metabolism.

• Increases the synthesis of ceramides and free fatty acids in the epidermis, thereby restoring the damaged lipid barrier and moisture balance in the skin, increasing the barrier function of the skin.
• The antioxidant protects the DNA of cells from UV damage.
• Brightens the skin, evens out its tone, blocking the transfer of melanosomes
• Effective in the battle against acne and post-acne.
• It has an anti-inflammatory effect by suppressing the activity of 3-5-cAMP-phosphodiesterase, suppresses the synthesis of triglycerides in sebocytes.

EFFECT OF VITAMIN A ON MELANOGENESIS

• Vitamin A and its derivatives are retinoids
• Normalize the differentiation of all cells of epithelial tissues
• Nuclear cell receptors control all biochemical processes of synthesis (control of melanin synthesis and abnormal growth of melanocyte processes)

HPR SERUM WITH GRANACTIVE RETINOID 2%

✓ Powerful renewal of skin cells
✓ Regulation of keratinization at all levels
✓ Correction of acne-like rashes
✓ Made in Switzerland

• RENOVAGE
• GRANDACTIVE RETINOID 2% (HPR retinoid)
• SWEET ALMOND OIL
• GRAPE SEED OIL

GRANACTIVE RETINOID 2% (HPR retinoid)

• The latest generation retinoid is an ester of retinoic acid. Does not convert into retinaldehyde and retinoic acid.
• It binds to retinoid receptors of skin cells
• Regulates the transfer of genetic information from DNA to RNA, stimulates the synthesis of collagen, which moisturizes glycosaminoglycans.
• Regulates the transfer of genetic information from DNA to RNA, stimulates the synthesis of collagen, which moisturizes glycosaminoglycans.
• Does not cause side effects, as it avoids metabolic breakdown, the components of which cause side effects and allergic reactions.
• Suppresses the activity of matrix metalloproteinases – enzymes that destroy collagen, which are activated under the influence of UVB radiation and other pathological factors.
• Thins the upper stratum corneum of the epidermis, which leads to a reduction in wrinkles.
• Normalizes keratinization processes

How to apply all this knowledge practically?

• Brightening regenerating care for the correction of pigmentation of various genesis
• Keratolytic action – a course of peels
• Daily use of sun protection and correctors – home care

Brightening regenerating care for the correction of pigmentation of various genesis

CLINICAL PICTURE:

✓ uneven relief and skin tone
✓ pigmentation of various genesis (including post-acne)
✓ signs of dehydration
✓ Hyperkeratosis

• Strengthening the skin barrier – restoring the balance of fatty acids
• Improving the health of keratinocytes – creating a favorable environment (natural moisturizing factor of the skin, normalization of microflora and pH)
• Evening out of the skin tone (working with existing pigmentation)
• Control of melanogenesis and prevention of the appearance of new spots

Brightening regenerating care for the correction of pigmentation of various genesis

1. Cleansing P172/ P173 + P174/P175
2. Exfoliation P200 Soft-peeling enzyme mask, rinse with water.
3. Massage P102, toning P174/P175
4. Р116 BRIGHTENING ALPAFLOR SERUM
5. Р189 SOFT BALANCE CLAY MASK 
6. P223 HPR-SERUM or Р107 RENEWING ENZYME AHA SERUM
7. Under eye cream Р204 Matrix eye cream
8. Finishing cream P111 4-SYNERGY BRIGHTENING CREAM P116 REVIT AHA CREAM

COMPLEX APPROACH OF RENEO COSMETICS: course program of 6 procedures

1. Brightening regenerating care for the correction of pigmentation of various genesis
2. Peeling care Peel-Expert Light / Shine
3. Brightening regenerating care for the correction of pigmentation of various genesis
4. Peeling care Peel-Expert Light / Shine
5. Main problem care (self-regulation, lifting, moisturizing)
6. Peeling care Peel-Expert Light / Shine

Alternation/combination of procedure protocols for comprehensive problem solving!

HOME CARE PRESCRIPTION

MORNING:

• Cleansing (P172) Comfort cleansing mousse
• Toning (P174) Calming tonic
• Serum (H118) Brightening alpaflor serum
• SPF Cream(H218 or H210)

EVENING:

• Cleansing (P172) Comfort cleansing mousse
• Toning (P174) Calming tonic
• Serum (H222) HPR serum or (H108) Renewing enzyme AHA serum
• Cream (H113) 4-synergy brightening cream or (H118) Revit AHA cream

EXTRA:

• Mask once a week (H119) Soft balance clay mask
• Mask once a week (H104) Soft-peeling enzyme mask
• Eye care (H143) Matrix eye cream

MELANOGENESIS CAN BE CONTROLLED WITH RENEO COSMETICS

✓ we know the physiological processes and features of melanogenesis
✓ we take into account the individual skin features
✓ we influence with the help of an effective combination of active components

= CORRECTION OF SKIN CONDITION AND PREVENTION