title: Alkaloid constituents from flower buds and leaves of sacred lotus (Nelumbo nucifera, Nymphaeaceae) with melanogenesis inhibitory activity in B16 melanoma cells.
abstract: Methanolic extracts from the flower buds and leaves of sacred lotus (Nelumbo nucifera, Nymphaeaceae) were found to show inhibitory effects on melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells. From the methanolic extracts, a new alkaloid, N-methylasimilobine N-oxide, was isolated together with eleven benzylisoquinoline alkaloids. The absolute stereostructure of the new alkaloid was determined from chemical and physicochemical evidence. Among the constituents isolated, nuciferine, N-methylasimilobine, (-)-lirinidine, and 2-hydroxy-1-methoxy-6a,7-dehydroaporphine showed potent inhibition of melanogenesis. Comparison of the inhibitory activities of synthetic related alkaloids facilitated characterization of the structure-activity relationships of aporphine- and benzylisoquinoline-type alkaloids. In addition, 3-30 μM nuciferine and N-methylasimilobine inhibited the expression of tyrosinase mRNA, 3-30 μM N-methylasimilobine inhibited the expression of TRP-1 mRNA, and 10-30 μM nuciferine inhibited the expression of TRP-2 mRNA.
authors.affiliation: Department of Pharmacognosy, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan.
authors.forename: Seikou
authors.initials: S
authors.lastname: Nakamura
authors.forename: Souichi
authors.initials: S
authors.lastname: Nakashima
authors.forename: Genzo
authors.initials: G
authors.lastname: Tanabe
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Oda
authors.forename: Nami
authors.initials: N
authors.lastname: Yokota
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Fujimoto
authors.forename: Takahiro
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Rika
authors.initials: R
authors.lastname: Sakuma
authors.forename: Tomoe
authors.initials: T
authors.lastname: Ohta
authors.forename: Keiko
authors.initials: K
authors.lastname: Ogawa
authors.forename: Shino
authors.initials: S
authors.lastname: Nishida
authors.forename: Hisako
authors.initials: H
authors.lastname: Miki
authors.forename: Hisashi
authors.initials: H
authors.lastname: Matsuda
authors.forename: Osamu
authors.initials: O
authors.lastname: Muraoka
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yoshikawa
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D035264:Flowers / Q000737:chemistry*; D006801:Humans; D008543:Melanins / Q000037:antagonists & inhibitors*; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D015394:Molecular Structure; D031653:Nelumbo / Q000737:chemistry*; D018515:Plant Leaves / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D008543:Melanins