title: Identification of coumarins from lemon fruit (Citrus limon) as inhibitors of in vitro tumor promotion and superoxide and nitric oxide generation.
abstract: Three coumarins were isolated as siginificant inhibitors of tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced Epstein-Barr virus (EBV) activation in Raji cells from the peel of lemon fruit. They were identified as 8-geranyloxypsolaren (LE-1), 5-geranyloxypsolaren (bergamottin, LE-2), and 5-geranyloxy-7-methoxycoumarin (LE-3), respectively, by spectroscopic analysis. Three isolates had no potential O(2)-scavenging and markedly suppressed TPA-induced superoxide (O(2)(-)) generation in differentiated human promyelocytic HL-60 cells. Furthermore, LE-1 and LE-3 reduced both lypopolysaccharide (LPS) and interferon-gamma (IFN-gamma)-induced nitric oxide (NO) generation in mouse macrophage RAW 264.7 cells. Similarly, they were found to be NO generation inhibitors rather than scavengers by measuring the extracellular L-citrulline levels. The occurrence of these coumarins in a lemon fruit was abundant in the flavedo of the peel based on quantitative analysis using high-performance liquid chromatography (HPLC). The present study suggests that the coumarins in lemon fruit are promising chemopreventive agents by inhibiting radical generation.
authors.affiliation: Central Research Laboratory of Pokka Corporation Ltd., Nishikasugai-gun, Aichi, Japan. yoshiaki_miyake@mr.pokka.co.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Miyake
authors.forename: A
authors.initials: A
authors.lastname: Murakami
authors.forename: Y
authors.initials: Y
authors.lastname: Sugiyama
authors.forename: M
authors.initials: M
authors.lastname: Isobe
authors.forename: K
authors.initials: K
authors.lastname: Koshimizu
authors.forename: H
authors.initials: H
authors.lastname: Ohigashi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000633:toxicity*; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D002957:Citrus / Q000737:chemistry*; D003374:Coumarins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D016166:Free Radical Scavengers; D018922:HL-60 Cells; D004854:Herpesvirus 4, Human / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry; D011994:Recombinant Proteins; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014775:Virus Activation / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D003374:Coumarins; D016166:Free Radical Scavengers; D008070:Lipopolysaccharides; D010936:Plant Extracts; D011994:Recombinant Proteins; D013481:Superoxides; D009569:Nitric Oxide; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate