title: Dichloromethane fraction of Cimicifuga heracleifolia decreases the level of melanin synthesis by activating the ERK or AKT signaling pathway in B16F10 cells.
abstract: Cimicifuga rhizoma has long been used in traditional Korean medicine. In particular, a Cimicifuga heracleifolia extract (CHE) was reported to inhibit the formation of glutamate and the glutamate dehydrogenase activity in cultured rat islet. Glutamate activates melanogenesis by activating tyrosinase. Accordingly, it was hypothesized that a CHE might inhibit the melanogenesis-related signal pathways including the inhibition of microphthalmia-associated transcription factor (MITF)-tyrosinase signaling and/or the activation of extracellular signal-regulated kinase (ERK)-Akt signaling. The results showed that CHE inhibits the cellular melanin contents, tyrosinase activity and expression of melanogenesis-related proteins including MITF, tyrosinase and tyrosinase-related protein (TRP)s in alpha-melanocyte-stimulating hormone-stimulated B16 cells. Moreover, CHE phosphorylates MEK, ERK1/2 and Akt, which are melanogenesis inhibitory proteins. The data suggest that CHE inhibits melanogenesis signaling by both inhibiting the tyrosinase directly and activating the MEK-ERK or Akt signal pathways-mediated suppression of MITF and its downstream signal pathway, including tyrosinase and TRPs. Therefore, C. heracleifolia would be a useful therapeutic agent for treating hyperpigmentation and an effective component in whitening and/or lightening cosmetics.
authors.affiliation: Department of Oriental Medicine, College of Oriental Medicine, Dongeui University, Busan, South Korea.
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Jang
authors.forename: Jun Hyuk
authors.initials: JH
authors.lastname: Lee
authors.forename: Byoung Won
authors.initials: BW
authors.lastname: Kang
authors.forename: Kyung Tae
authors.initials: KT
authors.lastname: Chung
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.forename: Byung Tae
authors.initials: BT
authors.lastname: Choi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D031885:Cimicifuga; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D008543:Melanins / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D008752:Methylene Chloride / Q000494:pharmacology*; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology
chemical_list: D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D010936:Plant Extracts; D008752:Methylene Chloride; D014442:Monophenol Monooxygenase; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D020930:MAP Kinase Kinase Kinases; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase