title: Hypo-pigmenting effect of sesquiterpenes from Inula britannica in B16 melanoma cells.
abstract: During the course of screens to identify anti-melanogenic agents from natural resources, we found that the methanol extract of the dried flower of Inula britannica L. inhibited melanin synthesis in cultured melanoma cells stimulated with 3-isobutyl-1-methylxanthine (IBMX). A bioassay-guided isolation of the chloroform fraction of the I. britannica using an in vitro melanogenesis inhibition assay led to the isolation of sesquiterpenes, 1-O-acetylbritannilactone (1), britannilactone (2) and neobritannilactone B (3). Compounds 1 and 2 significantly reduced melanin production in a dose-dependent manner with IC50 values of 13.3 and 15.5 μM, respectively, whereas compound 3 was found to be cytotoxic. Compound 1 also inhibited the tyrosinase activity only in cell based-systems. Western blot analysis indicated that compound 1 inhibited melanogenesis by activating extracellular signal-regulated kinase (ERK) and Akt signaling and also inhibiting cAMP related binding protein, which regulates its downstream pathway, including tyrosinase, tyrosinase related protein-1 and TRP-2. These results demonstrated that compound 1, a major sesquiterpene from the flowers of I. britannica, exhibited anti-melanogenic activity by suppression of tyrosinase expression via ERK and Akt signaling. Taken together, our results suggest that these compounds may act as potent natural skin-lightening agents.
authors.affiliation: Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang, Cheongwon, Chungbuk, 363-883, Republic of Korea.
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Choo
authors.forename: In-Ja
authors.initials: IJ
authors.lastname: Ryoo
authors.forename: Kwan Chul
authors.initials: KC
authors.lastname: Kim
authors.forename: Minkyun
authors.initials: M
authors.lastname: Na
authors.forename: Jae-Hyuk
authors.initials: JH
authors.lastname: Jang
authors.forename: Jong Seog
authors.initials: JS
authors.lastname: Ahn
authors.forename: Ick-Dong
authors.initials: ID
authors.lastname: Yoo
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D035264:Flowers; D038143:Inula / Q000737:chemistry; D008543:Melanins / Q000096:biosynthesis*; D008546:Melanoma, Experimental / Q000378:metabolism*; D051379:Mice; D014442:Monophenol Monooxygenase / Q000378:metabolism; D008517:Phytotherapy; D010858:Pigmentation / Q000187:drug effects*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D062327:Skin Lightening Preparations / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D008543:Melanins; D010936:Plant Extracts; D047428:Protein Kinase Inhibitors; D012717:Sesquiterpenes; D062327:Skin Lightening Preparations; D014442:Monophenol Monooxygenase; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases