Diosgenin inhibits melanogenesis through the activation of phosphatidylinositol-3-kinase pathway (PI3K) signaling

Life Sci. 2007 Jun 27;81(3):249-54. doi: 10.1016/j.lfs.2007.05.009. Epub 2007 May 24.


An increased level of melanin is characteristic of a large number of skin diseases, including acquired hyperpigmentation conditions such as melasma, post inflammatory melanoderma, and solar lentigo. Thus, there is an increasing need for the development of depigmenting agents. In order to evaluate the depigmenting capacity of diosgenin and elucidate its mechanism of action, several experiments were performed in B16 melanoma cells. Melanin content and Western blots for proteins that are involved in melanogenesis were assessed in this study. The melanin content was significantly inhibited by diosgenin. To clarify the mechanism of the depigmenting property of diosgenin, we examined the involvement of diosgenin in the phosphatidylinositol-3-kinase (PI3K) pathway. In this study, diosgenin inhibited the reduction of Akt and GSK 3beta phosphorylation induced by LY294,002, a PI3K inhibitor. In accordance with this result, production levels of MITF (microphthalmia-associated transcription factor) and tyrosinase were increased by diosgenin. These data suggest that diosgenin inhibits melanogenesis through the activation of the PI3K pathway. This suggestion was further confirmed by the fact that the increased production level of melanin by LY294,002 was reduced by diosgenin in B16 melanoma cells. Our study shows that diosgenin inhibits melanogenesis by activating the PI3K pathway, and also suggests that diosgenin may be an effective inhibitor of hyperpigmentation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chromones / pharmacology
  • Diosgenin / pharmacology*
  • Enzyme Inhibitors / pharmacology
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Melanins / antagonists & inhibitors*
  • Melanins / biosynthesis*
  • Melanoma, Experimental / enzymology
  • Melanoma, Experimental / metabolism
  • Mice
  • Microphthalmia-Associated Transcription Factor / metabolism
  • Monophenol Monooxygenase / antagonists & inhibitors
  • Monophenol Monooxygenase / biosynthesis
  • Morpholines / pharmacology
  • Oncogene Protein v-akt / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphoinositide-3 Kinase Inhibitors
  • Signal Transduction / drug effects*


  • Chromones
  • Enzyme Inhibitors
  • Melanins
  • Microphthalmia-Associated Transcription Factor
  • Morpholines
  • Phosphoinositide-3 Kinase Inhibitors
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Monophenol Monooxygenase
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, mouse
  • Oncogene Protein v-akt
  • Glycogen Synthase Kinase 3
  • Diosgenin