Abstract
Xanthium strumarium L. (Asteraceae) is traditionally used in Korea to treat skin diseases. In this study, we investigated the effects of a X. strumarium stem extract on melanin synthesis. It inhibited melanin synthesis in a concentration-dependent manner, but it did not directly inhibit tyrosinase, the rate-limiting melanogenic enzyme, and instead downregulated microphthalmia-associated transcription factor (MITF) and tyrosinase expression. MITF, the master regulator of pigmentation, is a target of the Wnt signaling pathway, which includes glycogen synthase kinase 3β (GSK3β) and β-catenin. Hence, the influence of X. strumarium stem extract on GSK3β and β-catenin was further investigated. X. strumarium induced GSK3β phosphorylation (inactivation), but the level of β-catenin did not change. Moreover, a specific GSK3β inhibitor restored X. strumarium-induced melanin reduction. Hence, we suggest that X. strumarium inhibits melanin synthesis through downregulation of tyrosinase via GSK3β phosphorylation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Line, Transformed
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Dose-Response Relationship, Drug
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Down-Regulation / drug effects
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Glycogen Synthase Kinase 3 / genetics
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Glycogen Synthase Kinase 3 / metabolism*
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Glycogen Synthase Kinase 3 beta
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Melanins / genetics
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Melanins / metabolism
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Melanocytes / cytology
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Melanocytes / drug effects*
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Melanocytes / metabolism
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Mice
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Microphthalmia-Associated Transcription Factor / antagonists & inhibitors*
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Microphthalmia-Associated Transcription Factor / genetics
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Microphthalmia-Associated Transcription Factor / metabolism
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Monophenol Monooxygenase / antagonists & inhibitors*
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Monophenol Monooxygenase / genetics
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Monophenol Monooxygenase / metabolism
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Phosphorylation
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Pigmentation / genetics
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Plant Extracts / isolation & purification
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Plant Extracts / pharmacology*
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Plant Stems / chemistry
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Wnt Signaling Pathway / drug effects
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Wnt Signaling Pathway / genetics
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Xanthium / chemistry*
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beta Catenin / genetics
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beta Catenin / metabolism
Substances
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CTNNB1 protein, mouse
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Melanins
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Microphthalmia-Associated Transcription Factor
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Mitf protein, mouse
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Plant Extracts
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beta Catenin
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Monophenol Monooxygenase
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Glycogen Synthase Kinase 3 beta
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Gsk3b protein, mouse
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Glycogen Synthase Kinase 3