ERK Activation by Fucoidan Leads to Inhibition of Melanogenesis in Mel-Ab Cells

Abstract

Fucoidan, a fucose-rich sulfated polysaccharide derived from brown seaweed in the class Phaeophyceae, has been widely studied for its possible health benefits. However, the potential of fucoidan as a possible treatment for hyperpigmentation is not fully understood. This study investigated the effects of fucoidan on melanogenesis and related signaling pathways using Mel-Ab cells. Fucoidan significantly decreased melanin content. While fucoidan treatment decreased tyrosinase activity, it did not do so directly. Western blot analysis indicated that fucoidan downregulated microphthalmia-associated transcription factor and reduced tyrosinase protein expression. Further investigation showed that fucoidan activated the extracellular signal-regulated kinase (ERK) pathway, suggesting a possible mechanism for the inhibition of melanin synthesis. Treatment with PD98059, a specific ERK inhibitor, resulted in the recovery of melanin production. Taken together, these findings suggest that fucoidan inhibits melanogenesis via ERK phosphorylation.

The promise of marine molecules as cosmetic active ingredients

“…Song et al . reported that this sulphated polysaccharide from phaeophyte Fucus vesiculosus downregulated melanin synthesis via the activation of the extracellular signal‐related kinase (ERK) pathway, which has been shown to cause the degradation of microphthalmia‐associated transcription factor – which is involved in melanin production . This was shown using Mel‐Ab cells – a murine melanocyte cell line which is particularly efficient in producing melanin .…”

“…Fucoidan, also a phaeophyte secondary metabolite, has been documented as a potential anti‐pigment treatment, with evidence for its mechanism of indirect melanogenesis inhibition , but has not yet been pursued as a cosmetic ingredient. Song et al .…”

Discovery of new depigmenting compounds and their efficacy to treat hyperpigmentation: Evidence from in vitro study

“…Several depigmenting compounds showed antimelanogenic activity via ERK‐mediated downregulation of MITF. For instance, Eucalyptus camaldulensis flower EO, Artocarpus communis extracts, geranylgeranylacetone (C 23 H 37 O), menadione (C 11 H 8 O 2 ), β‐lapachone (C 15 H 14 O 3 ), fucoidan, Withania somnifer, dipeptides (proline‐serine [C 8 H 16 O 5 N 2 ] and valine‐serine [C 8 H 18 O 5 N 2 ]) inhibit melanogenesis through downregulating of MITF via ERK signaling pathways as demonstrated using various cell line models (ie, B16F10, Mel‐Ab cells, human epidermal equivalents [HEE], and Melanoderm™) . E camaldulensis EO and aglycone of Rh 4 differ from other depigmenting compounds in which they also downregulate protein kinase A (PKA) where E camaldulensis EO but not aglycone of Rh 4 also regulates mitogen‐activated protein kinases p38 (p38 MAPK) .…”

“…Specific bioactive compounds in W somnifer extract responsible for such action are forthcoming topic of interest for further evaluation. On the other hand, it was suggested that compounds such as oleoylethanolamide (C 20 H 39 NO 2 ), lysophosphatidic acid (C 21 H 41 O 7 P), Zeolite‐4A, C2‐ceramides (C 19 H 37 NO 3 ), sphingosylphosphorylcholine (C 23 H 49 N 2 O 5 P), betulinic acid (C 30 H 48 O 3 ), c‐phycocyanin (C 32 H 45 O 6 N 4 ), and fucoidan (fucose‐rich sulfated polysaccharide) were capable of reducing melanin synthesis by either inducing MITF degradation or blocking MITF expression, via AKT (protein kinase B) and/or ERK pathway …”

“…Initial assay development activities identified the shortest in‐life assay phase sufficiently sensitive to identify melanogenesis modulators . On the other hand, immortalized melanocytes (ie, melan‐a and mel‐Ab) had advantage in terms of results’ consistency and reproducibility in relation to the consistent cell activity and reaction even after many subcultures . Moreover, they did not acquire UV or even hormone stimulant to synthesize a large amount of melanin .…”