title: Lyoniresinol inhibits melanogenic activity through the induction of microphthalmia-associated transcription factor and extracellular receptor kinase activation.
abstract: Lyoniresinol was one of the eight lignans purified from methanol extract of Vitex negundo and was shown to have robust tyrosinase inhibitory capacity. However, the mechanism of its action is not known. Hence, the goal of the current study was to study the effects of Lyoniresinol on cytotoxicity and melanin content in murine B16F10 melanoma cells and to delineate the underlying mechanism of tyrosinase inhibition. Lyoniresinol was purified from methanol extract of Vitex negundo root and when tested in B16F10, cells showed robust anti-melanogenic activity. It caused the downregulation of microphthalmia-associated transcription factor (MITF) and tyrosinase steady state protein expression levels. Flow cytometry analysis of Lyoniresinol-treated cells showed that the latter activates extracellular receptor kinase (ERK) phosphorylation, which causes MITF protein degradation and suppression of tyrosinase activity. Lyoniresinol decreased tyrosinase activity and melanin biosynthesis in B16F10 cells by activating ERK signaling, which downregulated MITF, tyrosinase, but not TRP-1 and TRP-2 protein expression. Contingent to more vigorous in vitro and in vivo experiments, Lyoniresinol can perhaps be incorporated into clinical dermatologic use as a skin lightening agent.
authors.affiliation: Dermatology Department, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Huiyu
authors.initials: H
authors.lastname: Liu
authors.forename: Xiaoxin
authors.initials: X
authors.lastname: Sui
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Li
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D000840:Anisoles / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D007370:Interferon Type I / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008543:Melanins / Q000378:metabolism*; D008546:Melanoma, Experimental; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics / Q000378:metabolism*; D014442:Monophenol Monooxygenase / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology*; D010766:Phosphorylation; D011257:Pregnancy Proteins / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D062327:Skin Lightening Preparations / Q000494:pharmacology*; D015533:Transcriptional Activation / Q000187:drug effects*
chemical_list: D000840:Anisoles; D007370:Interferon Type I; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D009281:Naphthalenes; D011257:Pregnancy Proteins; D062327:Skin Lightening Preparations; C020947:interferon tau; C502379:lyoniresinol; D014442:Monophenol Monooxygenase; D048049:Extracellular Signal-Regulated MAP Kinases; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase