Medical Chronicle November/December 2013 | Page 54

DERMATOLOGY
Topical treatment of

hyperpigmentation
Hyperpigmentary disorders
such as melasma, actinic and senile
lentigines are a major cosmetic
concern. Therefore, many topical
products are available, containing
various active ingredients aiming
to reduce melanin production and
distribution. The most prominent target
for inhibitors of hyperpigmentation
is tyrosinase, the key regulator of
melanin production. Many inhibitors
of tyrosinase are described in the
literature; however, most of them lack
clinical efficacy.

Methods
Kolbe et al were interested in
evaluating the inhibition of skin
pigmentation by well-known
compounds with skin-whitening
activity like hydroquinone, arbutin,
kojic acid a nd 4-n-butylresorcinol.
Researchers compared the inhibition
of human tyrosinase activity in a
biochemical assay as well as inhibition
of melanin production in MelanoDerm
skin model culture. For some
compounds, the in vivo efficacy was
tested in clinical studies.

54 MEDICAL CHRONICLE NOVEMBER/DECEMBER 2013

Results
Arbutin and hydroquinone only weakly
inhibit human tyrosinase with a halfmaximal inhibitory concentration
(IC(50)) in the millimolar range. Kojic
acid is 10 times more potent with an
IC(50) of approximately 500?mol/l.
However, by far the most potent
inhibitor of human tyrosinase is
4-n-butylresorcinol with an IC(50)
of 21?mol/l. In artificial skin models,
arbutin was least active with an IC(50)
for inhibition of melanin production
>5000?mol/l.
Kojic acid inhibited with an
IC(50) >400?mol/l. Interestingly,
hydroquinone inhibited melanin
production in MelanoDerms with an
IC(50) below 40?mol/l, probably due to
a mechanism different from tyrosinase
inhibition. Again, 4-n-butylresorcinol
was the most potent inhibitor with an
IC(50) of 13.5?mol/l.
In vivo efficacy of 4-n-butylresorcinol was confirmed in clinical
studies. Subjects with age spots on the
forearm were treated twice daily for
two age spots with a formula containing
4-n-butylresorcinol and two control age

spots with the corresponding vehicle.
Within eight weeks, 4-n-butylresorcinol
reduced visibly the appearance of age
spots, while the control spots showed
no improvement. A second study
showed that 4-butylresorcinol was
more effective than 4-hexylresorcinol
and 4-phenylethylresorcinol.

Conclusion
The present in vitro and in vivo data
prove the high inhibitory capacity
of 4-n-butylresorcinol on human
tyrosinase activity, exceeding by
far the potency of hydroquinone,
arbutin and kojic acid. The
resulting clinical improvement of
skin hyperpigmentations reveals
4-n-butylresorcinol as a very valuable
active compound for the management
of pigmentation disorders.
Reference
Kolbe L, Mann T, Gerwat W, et al.
4-n-butylresorcinol, a highly effective
tyrosinase inhibitor for the topical treatment
of hyperpigmentation. J Eur Acad Dermatol
Venereol. 2013 Suppl 1:19-23. doi: 10.1111/
jdv.12051.