title: Antioxidative and melanogenesis-inhibitory activities of caffeoylquinic acids and other compounds from moxa.
abstract: The MeOH extract of moxa, the processed leaves of Artemisia princeps PAMP. (Asteraceae), exhibited potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity and melanogenesis-inhibitory activity in α-melanocyte-stimulating hormone (α-MSH)-stimulated B16 melanoma cells. Eight caffeoylquinic acids, 1 and 6-12, five flavonoids, 13-17, two benzoic acid derivatives, 18 and 19, three coumarin derivatives, 20-22, four steroids, 23-26, and six triterpenoids, 27-32, were isolated from the MeOH extract. Upon evaluation of compounds 1, 6-23, and four semisynthetic caffeoylquinic acid esters, 2-5, for their DPPH radical-scavenging activity, 15 compounds, 1-13, 17, and 19, showed potent activities (IC(50) 3.1-16.8 μM). The 15 compounds exhibited, moreover, potent inhibitory activities (51.1-92.5% inhibition) against peroxidation of linoleic acid emulsion at 10 μg/ml concentration. In addition, when 27 compounds, 1-8, 10, 12, 13, 15-18, 20-25, and 27-32, were evaluated for their inhibitory activity against melanogenesis in α-MSH-stimulated B16 melanoma cells, five caffeoylquinic acids, i.e., chlorogenic acid (1), ethyl chlorogenate (3), propyl chlorogenate (4), isopropyl chlorogenate (5), and butyl chlorogenate (6), along with homoorientin (17) and vanillic acid (18), exhibited inhibitory activities with 33-62% reduction of melanin content at 100 μM concentration with no or almost no toxicity to the cells (89-114% of cell viability at 100 μM). Western blot analysis showed that compound 6 reduced the protein levels of microphtalmia-associated transcription factor (MITF), tyrosinase, tyrosine-related protein 1 (TRP-1), and TRP-2 mostly in a concentration-dependent manner, suggesting that this compound inhibits melanogenesis on α-MSH-stimulated B16 melanoma cells by, at least in part, inhibiting the expression of MITF, followed by decreasing the expression of tyrosinase, TRP-1, and TRP-2. Furthermore, four compounds, 13, 15, 16, and 30, exhibited cytotoxicities against HL60 human leukemia cell line (IC(50) 7.0-11.1 μM), and nine compounds, 14-16, 23, 26-28, 31, and 32, showed inhibitory effects (IC(50) 272-382 mol ratio/32 pmol 12-O-tetradecanoylphohrbol-13-acetate (TPA)) against Epstein-Barr virus early antigen (EBV-EA) activation induced by TPA in Raji cells.
authors.affiliation: College of Science and Technology, Nihon University, 1 - 8-14 Kanda Surugadai, Tokyo 101-8308, Japan. akihisa_toshihiro@yahoo.co.jp
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Akihisa
authors.forename: Kohta
authors.initials: K
authors.lastname: Kawashima
authors.forename: Masashi
authors.initials: M
authors.lastname: Orido
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Akazawa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Ayako
authors.initials: A
authors.lastname: Yamamoto
authors.forename: Eri
authors.initials: E
authors.lastname: Ogihara
authors.forename: Makoto
authors.initials: M
authors.lastname: Fukatsu
authors.forename: Harukuni
authors.initials: H
authors.lastname: Tokuda
authors.forename: Jizaemon
authors.initials: J
authors.lastname: Fuji
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity; D019306:Artemisia / Q000737:chemistry*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D008543:Melanins / Q000037:antagonists & inhibitors / Q000378:metabolism; D009074:Melanocyte-Stimulating Hormones / Q000037:antagonists & inhibitors / Q000378:metabolism; D008546:Melanoma, Experimental / Q000378:metabolism / Q000473:pathology; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D018515:Plant Leaves / Q000737:chemistry; D011801:Quinic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity
chemical_list: D000975:Antioxidants; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D010936:Plant Extracts; C472707:caffeoylquinic acid; D011801:Quinic Acid; D009074:Melanocyte-Stimulating Hormones; D014442:Monophenol Monooxygenase