Antimelanogenic effect of c-phycocyanin through modulation of tyrosinase expression by upregulation of ERK and downregulation of p38 MAPK signaling pathways

Cpc-induced inhibitory effects on melanin synthesis and tyrosinase expression were evaluated. The activity of MAPK pathways-associated molecules such as MAPK/ERK and p38 MAPK, were also examined to explore Cpc-induced antimelanogenic mechanisms. Additionally, the intracellular localization of Cpc was investigated by confocal microscopic analysis to observe the migration of Cpc.Cpc significantly (P < 0.05) reduced both tyrosinase activity and melanin production in a dose-dependent manner. This phycobiliprotein elevated the abundance of intracellular cAMP leading to the promotion of downstream ERK1/2 phosphorylation and the subsequent MITF (the transcription factor of tyrosinase) degradation. Further, Cpc also suppressed the activation of p38 causing the consequent disturbed activation of CREB (the transcription factor of MITF). As a result, Cpc negatively regulated tyrosinase gene expression resulting in the suppression of melanin synthesis. Moreover, the entry of Cpc into B16F10 cells was revealed by confocal immunofluorescence localization and immunoblot analysis.Cpc exerted dual antimelanogenic mechanisms by upregulation of MAPK/ERK-dependent degradation of MITF and downregulation of p38 MAPK-regulated CREB activation to modulate melanin formation. Cpc may have potential applications in biomedicine, food, and cosmetic industries.C-phycocyanin (Cpc), a major type of phycocyanin of phycobilisome in spirulina, has been suggested to exhibit radical-scavenging property [1] to reduce inflammatory responses [2,3] and oxidative stress [1,4]. This phycobiliprotein also induces HeLa cell apoptosis [5,6] enhances wound healing [7], retards platelet aggregation [8,9] and acts as a photodynamic agent to eradicate cancer cells in vitro [10,11]. Moreover, animal studies revealed that Cpc possesses protective effects on tetrachloride-induced hepatocyte damage [12] and oxalate-resulted nephronal impartment [13], and oral administration of Cpc successfully relieves the pathogenicit