New biological results obtained in the Fight against Skin Pigmentation Disorders

Skin pigmentation is an international preoccupation. Natural or photo-induced ageing, hormonal disorders (contraceptives, pregnancy, menopause, etc.), repeated exposure to the sun and irritation or inflammation reactions lead to the appearance of skin pigment problems. The complexion is not uniform and highly unattractive marks appear on the skin.


Many cosmetic products claiming a “lightening” action in fact have very mediocre effectiveness and non-negligible toxicity, and are difficult to formulate.



SEPPIC has developed a major “lightening” research program, focusing its attention on the effects of a precursor molecule as a major factor in the regulation of skin pigmentation, melanotropin (or alpha-MSH). Melanotropin controls tyrosinase activity, melanin (eumalanin) synthesis and melanosome transfer.



I SEPIWHITE MSH: a new mode of action

Developing a concept based on innovation, effectiveness and tolerance, SEPPIC has developed a new lightening active ingredient, SEPIWHITE MSH. A new molecule, this active ingredient has a complete and innovative mode of action. An alpha-MSH antagonist, SEPIWHITE MSH is our solution for combating pigment problems. Maintaining skin integrity, it acts upstream of melanogenesis on all the steps in the pigment cascade induced by melanotropin. Its depigmenting effectiveness has been proven in vitro and in vivo on healthy volunteers.


Novel pathway

How does � MSH act on melanocytes? By binding to MC1R receptors, � MSH stimulates the � subunit of the G protein. The G protein activates adenylate cyclase, which increases the intracellular cAMP rate. cAMP activates the protein kinase A which then phosphorylates the tyrosinase. The phosphorylated

tyrosinase becomes active and stimulates melanogenesis.



Acting as an antagonist of � MSH which means “upstream of melanogenesis”, SEPIWHITE MSHT™ will inhibit all the steps of pigmentation cascade induced by the melanotropin.


Its lightening effect reached through an original mode of action has been demonstrated firstly in vitro:

  1. Competition with melanotropin for the MCIR receptors of the melanocytes (binding test for MC1R receptor)


  1. Inhibition of adenylate cyclase


  1. Inhibition of intracellular cAMP contents


  1. Inhibition of Protein Kinase A


  1. Inhibition of tyrosinase (the effect on tyrosinase appears to be related to SEPIWHITE MSH behaving as a decoy substrate)


6. Inhibition of melanogenesis


This pathway is original and unique compared to that described for other lightening agents, such as hydroquinone, arbutin, kojic acid or Magnesium Ascorbyl Phosphate (VCPMG), which do not involve the receptor of � MSH. In vitro tests have shown the enhanced effectiveness of SEPIWHITE MSH™ compared to these active reference lightening agents.

II SEPIWHITE MSH™: lightening effect confirmed on melanocytes

The lightening activity of SEPIWHITE MSH™ in comparison to the reference active ingredients used customarily (arbutine, kojic acid, VCPMG, hydroquinone) has been then proven on B16 melanocytes cultured under three types of conditions:

  1. SEPIWHITE MSH™ has a spontaneous lightening action through an inhibition of basal melanogenesis (proven with SEPIWHITE cultivated with melanocytes alone)
  2. SEPIWHITE MSH™ inhibits the melanogenesis stimulated by alpha MSH (antagonist effect towards melanotropin) (proven with SEPIWHITE MSH cultivated with melanocytes in the presence of alpha MSH)
  3. SEPIWHITE MSH™ inhibits the melanogenesis stimulated by UVB (proven with SEPIWHITE MSH cultivated with melanocytes cultivated in the presence of UVB)

III “FLASH” activity of SEPIWHITE MSHTM on pigmented reconstructed epidermis

The lightening activity of SEPIWHITE MSHTM formulated at 2% has also been confirmed on pigmented reconstructed epidermis (3D model of organized human skin) after 7 days of topical application. Its activity was compared with those of arbutine and kojic acid, also formulated at 2%, and that of hydroquinone formulated at 0.1% (because of its cytotoxicity).

Besides its good reduction of melanin content (measured by spectrophotometry) SEPIWHITE MSH™ is the only active showing a “measurable” lightening effect at the surface of the skin after 7 days of topical treatment (increase of L*, decrease of a* and decrease of b* in chromametry). Its efficacy is greater and faster than arbutin, kojic acid or hydroquinon. This “fast” activity must be due to its lipoaminoacid form, and it's ideal amphiphilic structure being well adapted to reach the targeted melanocytes located in the lower layers of epidermis.



IV The “5 proofs” of SEPIWHITE MSHTM in vivo effectiveness

Finally, the lightening evaluation of SEPIWHITE MSH™ formulated at 2% has been evaluated in a new in vivo study performed on 30 Asian volunteers (Bangkok). The formula has been applied on the face twice a day for 3 months and the lightening effectiveness of SEPIWHITE MSH was assessed before treatment (D0), after 2 months of treatment (D56) and after 3 months of treatment (D84).


  1. Decrease of melanic pigments at the skin surface

 By the second month of treatment, there were fewer melanic pigments located in the corneocytes (surface cells of the stratum corneum). The skin is visibly clearer.

  1. Even skin tone effect

By the second month of treatment, SEPIWHITE MSH™ significantly increases even skin tone (increase of L* parameter). The ITA (Individual Typological Index) also increases significantly from the second month of treatment. The tone is sublimated, more radiant.

Determination of the luminosity (parameter L*) by chromametry:



  1. Lightening effect

 By the second month of treatment, the skin was significantly lightened (decrease of the melanin index). The pigmented areas fade away, the tone becomes more uniform.

Measurement of skin color reduction (melanin index) using a Mexameter:


  1. Lightening effect on pigmented areas:

 By the second month of treatment, the hyperpigmented areas are visibly and significantly lightened.

Clinical and visual examination done by a dermatologist:


  1. Overall assessment of formula 6911 by the panellists after three months of treatment

93% of the volunteers appreciated formula 6911 for its effectiveness and comfort. Moreover, tolerance was excellent on all the persons tested.


SEPIWHITE MSH™ shows excellent lightening effectiveness.




V Tolerance

More efficient than the reference lightening agents (arbutin, magnesium ascorbyl phosphate, kojic acid and hydroquinone), SEPIWHITE MSH™ is well tolerated at the recommended dosage (2%).

VI Galenic form

 SEPIWHITE MSH can be used easily in gel, gel-cream, simple and multiple emulsion, lotion, tonic and hygiene product formulas. Completely stable, its use is particularly recommended at 2% in any type of formula where lightening activity is sought.

SEPIWHITE MSH is fully compatible in formulation with other lightening active ingredients such as the AHAs or kojic acid (formulas with pH < 5), arbutine, hydroquinone or VCPMG (formulas with pH > 7) and is totally compatible in formulation with sun screens.

Formulation studies have proven the excellent stability of SEPIWHITE MSH formulated at 2%. No change of colour or odour has been observed in the end formulas over time or according to temperature. More, SEPIWHITE MSH can be formulated easily in clear, colourless lotions, whether they are aqueous, hydroalcoholic or hydroglycolic.

Combining      innovation,       safety       and      effectiveness, SEPIWHITE MSH™ operates in an original and unique way. A new generation of lightening agents is born.


    Shop now

    You can use this element to add a quote, content...