Decursin prevents melanogenesis by suppressing MITF expression through the regulation of PKA/CREB, MAPKs, and PI3K/Akt/GSK-3β cascades

• DOI: 10.1016/j.biopha.2022.112651
• Publication Date: 2022-01-18T04:39:01Z
• Authors: Hyungyeong Choi; Jeong-Hyun Yoon; Kumju Youn; Mira Jun
• Keywords: Microphthalmia-associated transcription factor

Abnormal melanin synthesis upon UV exposure causes excessive oxidative stress, which leads to skin hyperpigmentation disorders such as freckles, melisma, and age spots. The present study investigated the anti-melanogenic effects of decursin underlying mechanism using multiple approaches. Decursin exhibited no cytotoxicity significantly reduced intracellular tyrosinase activity content in B16F10 melanoma cells. also inhibited expression melanogenic enzymes tyrosinase-related protein (TRP)- 1, but not TRP-2. Mechanistically, suppressed through cAMP-dependent kinase (PKA)/cAMP response element-binding (CREB)-dependent downregulation microphthalmia-associated transcription factor (MITF), a master melanogenesis. Further, exerted by downregulating p38 signaling pathway upregulating extracellular signal-regulated (ERK) phosphatidylinositol 3 (PI3K)/protein B (Akt)/glycogen kinase-3β (GSK-3β) cascades. silico analysis showed that formed specific interactions with residues upstream regulators MITF optimal pharmacokinetic profiles, including permeability sensitization. Finally, were confirmed ex vivo 3D human models, suggesting its applicability protective agent against hyperpigmentation.