Identification of coumarins from lemon fruit (Citrus limon) as inhibitors of in vitro tumor promotion and superoxide and nitric oxide generation.
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.
Miyake
Y
Y
Central Research Laboratory of Pokka Corporation Ltd., Nishikasugai-gun, Aichi, Japan. yoshiaki_miyake@mr.pokka.co.jp
Murakami
A
A
Sugiyama
Y
Y
Isobe
M
M
Koshimizu
K
K
Ohigashi
H
H
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
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