Phloridzin-induced melanogenesis is mediated by the cAMP signaling pathway

Food Chem Toxicol. 2009 Oct;47(10):2436-40. doi: 10.1016/j.fct.2009.06.039. Epub 2009 Jul 2.


Melanogenesis is a physiological process that results in the synthesis of melanin pigments, which play a crucial protective role in protection against skin photocarcinogenesis. Phloridzin is a phloretin 2'-glucoside that is found in many parts of the apple tree that reportedly increases tyrosinase activity and melanin contents through inhibition of protein kinase C (PKC) activity in B16 melanoma cells. In this study, we attempted to accurately determine the effects and mechanisms of action of phloridzin on melanogenesis. Specifically, we observed that phloridzin-induced a dose-dependent increase in tyrosinase activity and melanin contents, and that these changes were accompanied by an increase in the levels of tyrosinase and the tyrosinase-related proteins, TRP-1 and TRP-2. Furthermore, the cAMP-dependent protein kinase A (PKA) inhibitor H89 impaired the response of the tyrosinase activity and melanin synthesis to phloridzin. Additionally, phloridzin stimulated cAMP production and phosphorylation of the cAMP-response element binding protein (CREB). Taken together, the results of this study indicate that phloridzin increases tyrosinase gene expression through the cAMP signaling pathway, thereby leading to the stimulation of melanogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CREB-Binding Protein / drug effects
  • CREB-Binding Protein / metabolism
  • Cell Line, Tumor
  • Cyclic AMP-Dependent Protein Kinases / drug effects*
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology*
  • Intramolecular Oxidoreductases / drug effects
  • Intramolecular Oxidoreductases / metabolism
  • Melanins / metabolism*
  • Melanoma / drug therapy*
  • Melanoma / metabolism
  • Mice
  • Monophenol Monooxygenase / drug effects
  • Monophenol Monooxygenase / metabolism
  • Oxidoreductases / drug effects
  • Oxidoreductases / metabolism
  • Phlorhizin / pharmacology*
  • Signal Transduction / drug effects
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / metabolism


  • Enzyme Inhibitors
  • Melanins
  • Phlorhizin
  • Oxidoreductases
  • tyrosinase-related protein-1
  • Monophenol Monooxygenase
  • CREB-Binding Protein
  • Crebbp protein, mouse
  • Cyclic AMP-Dependent Protein Kinases
  • Intramolecular Oxidoreductases
  • dopachrome isomerase