Mushrooms aren’t people! Or why human clinical studies are the gold standard

Marketing language of skincare often leaves out on “what” the tests were done. Leading the consumer to believe that the testing was done on someone like them.

For many products aimed at treating hyperpigmentation, the claims are often based on the inhibition of tyrosinase, an enzyme found in plants and animals that plays a role in the creation of melanin. So it makes sense why inhibiting the effect of tyrosinase would lead to a decrease in melanin production in the skin. What’s often left out, is that most of these tests are performed on tyrosinase derived from the Agaricus bisporus mushroom.

What’s important to understand is that though the enzyme group may be the same, the structure and environment isn’t. Mushroom tyrosinase and human tyrosinase (hTyr) have different catalytic activities and substrate affinities.

Mushroom tyrosinase is easily accessed, commercially available, and cheap. Human tyrosinase until recently was difficult to produce and isolate.

As early as 2013, a group of researchers led by Petra Cordes were able to express hTyr in human kidney cells and then isolate them. This allowed them to 3D map the enzyme and use them in further tests.

Building upon this, scientists from Beiersdorf screened 50,000 compounds to see which ones effectively inhibited hTyr. What they found was interesting, but not surprising.

Some compounds which are very effective in inhibiting mushroom tyrosinase (like hydroquinone, arbutin, and kojic acid) had a reduced or minimal effect on hTyr.

Of the 50,000 compounds tested, thiazolyl-resorcinols were the most promising. They then modified it to be compatible with topical formulations leading to isobutylamido thiazolyl resorcinol.

An interesting thing they found about hydroquinone and its precursors like arbutin was their activity may be due to a cytotoxic effect on melanocytes. Their experiment showed a long-term reduction in melanocyte activity even after the hydroquinone or arbutin was stopped.

The group at Beiersdorf then went on to test 0.2% isobutylamido thiazolyl resorcinol on a group of humans for 4 weeks and were able to see a statistically significant and clinically relevant decrease in hyperpigmentation.

It’s very likely that Beiersdorf will patent the use of isbutlamido thiazolyl resorcinol for treating hyperpigmentation, especially if further human clinical trials are positive, but their methods for performing this test on human tyrosinase in MelanoDerm skin models have been shared with the scientific community.

Mann T, Gerwat W, Batzer J, Eggers K, Scherner C, Wenck H, Stäb F, Hearing VJ, Röhm K-H, Kolbe L, Inhibition of Human Tyrosinase Requires Molecular Motifs Distinctively Different from Mushroom Tyrosinase, The Journal of Investigative Dermatology (2018), doi: 10.1016/j.jid.2018.01.019.