Natural Cosmeceutical Ingredients for Hyperpigmentation

January 2016 | Volume 15 | Issue 1 | Original Article | 26 | Copyright © January 2016

Noelani Gonzalez MD and Maritza Perez MD

Mount Sinai Hospital, New York, NY

As Dermatologists caring for patients with hyperpigmentation problems, we are always looking for more alternative therapies. Hydroquinone (HQ) is still the standard of care. However, traditional depigmenting agents such as HQ and corticosteroids, although highly effective, can raise safety concerns including exogenous ochronosis, atrophy, carcinogenesis and local and systemic untoward effects with long term use. Therefore, we need to investigate non-prescription natural alternatives. This manuscript presents many of the natural ingredients found in cosmeceuticals for the treatment of hyperpigmentation and their mechanisms of action. It will also describe the melanocyte activation pathways and how each of these ingredients interferes with it.

J Drugs Dermatol. 2016;15(1):26-34.


The melanocyte activation pathway, melanogenesis, is a complicated one. However if we divide it in four components it is easier to dissect.
The melanocyte can be activated on the cell surface by various stimulants. These include hormones (MSH, ACTH), systemic or local inflammation (acne), and external environmental insults (ultraviolet light leading to the production of free radicals and prostaglandins). All these stimulants induce the up regulation of the tyrosinase gene, inducing tyrosinase gene transcription. Tyrosine then goes thru its activation process including glycosylation. Activated tyrosine then is capable of turning tyrosine into DOPA, which is subsequently turned into DOPA Quinone, and then into Melanin. Finally melanin is package into melanosomes and transferred to keratinocytes.
To effectively reduce the melanogenesis process, the pathway has to be blocked at multiple levels simultaneously. For simplification purposes, the blocking of melanogenesis has been divided into four different compartments: 1. Reduction of melanocyte activation, 2. Inhibition of melanin synthesis, 3. Reduction of melanin transfer, 4. Exfoliation of keratinocytes containing melanosomes (Figure 1).
  • Reduce Melanocyte Activation
    • 4-Ethoxybenzaldehyde- anti-inflammatory and prostaglandin E2 suppressor
    • Tetrahexyldecyl Ascorbate- stable, lipid soluble vitamin C
    • Tetrapeptide-30 reduces keratinocyte-induced activation of melanocytes
    • Broad Spectrum Sun Blocks with Zinc oxide, titanium dioxide and iron oxide- impedes melanocyte stimulation blocking UVB, UVA, visible light
    • Undecylenoyl phenylalanine- sepiwhite-inhibits melanotropin
  • Inhibit Melanin Synthesis
    • Retinol-inhibits tyrosinase activity, reduction in the size of cellular organelles related to the synthesizing activity of the melanocyte (Golgi apparatus and endoplasmic reticulum)
    • Linoleic Acid-suppresses melanogenesis and tyrosinase activity
    • Glabridin (Licorice Extract) has been shown to prevent UVB-induced pigmentation and to inhibit tyrosinase activity, superoxide anion production and cyclo-oxygenase activity
    • Mulberry (Licorise extract from Morus alba) inhibits tyrosinase activity, superoxide anion production and cyclo-oxygenase activity
    • Hexylresorcinol- inhibits tyrosinase activity
    • Tetrapeptide-30
    • Tetrahexyldecyl Ascorbate- reduces oxidized dopaquinone, interrupting DHICA oxidation and interacting with copper ions at the active site of tyrosinase
    • Kojic Acid naturally occurring hydrophilic fungal metabolite that inactivates tyrosinase by chelating copper atoms as well as suppressing the tautomerization of dopachrome 
    • Arbutin-derivative of hydroquinone found in cranberries, blueberries, wheat and pears competitively and reversely binding tyrosinase
    • Tochopherols – lipophilic antioxidant that increase in intracellular glutathione and the inhibition of tyrosinase
    • N-Acetyl Glucosamine- inhibits tyrosinase glycosilation
    • Aloesin is a natural hydroxymethyl chromone compound derived from aloe vera plants that competitively inhibits the function of tyrosinase by inhibiting the hydroxylation of tyrosine to DOPA and oxidation of DOPA to dopaquinone