Dichloromethane fraction of Cimicifuga heracleifolia decreases the level of melanin synthesis by activating the ERK or AKT signaling pathway in B16F10 cells.
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.
Jang
Ji Yeon
JY
Department of Oriental Medicine, College of Oriental Medicine, Dongeui University, Busan, South Korea.
Lee
Jun Hyuk
JH
Kang
Byoung Won
BW
Chung
Kyung Tae
KT
Choi
Yung Hyun
YH
Choi
Byung Tae
BT
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
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