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.

Characterization of phenolic profile and antioxidant capacity of different fruit part from lemon (Citrus limon Burm.) cultivars

“…The eriocitrin (eriodictyol 7-rutinoside) from lemon fruit was isolated and its antioxidant capacity was evaluated (Miyake et al 1997). The coumarins from lemon fruit was identified and the inhibition for tumor promotion and superoxide and nitric oxide generation was characterized (Miyake et al 1999). New limonoid glycosides was isolated and their Electronic supplementary material The online version of this article (doi:10.1007/s13197-017-2544-5) contains supplementary material, which is available to authorized users.…”

Scavenging capacity of superoxide radical and screening of antimicrobial activity of Castanea sativa Mill. extracts

“…They also have anti-inflammatory activity and anti-carcinogenic properties (Miyake et al 1999). On the other hand, the activity of these compounds as food lipid antioxidants is well known (Rice-Evans et al 1997), and this fact promoted studies of extracts from different plants containing them.…”

Coumarin and Flavone Derivatives from Estragon and Thyme as Inhibitors of Chemical Mediator Release from RBL-2H3 Cells

“…No cytotoxicity was apparent when the concentration of a coumarin derivative was less than 1:0 Â 10 À4 M. Coumarins inhibited IgE-mediated histamine release from RBL-2H3 cells as well as that of -hexosaminidase release (data not shown). Coumarin derivatives occur in various spice plants, and have been reported to have antitumoral, 15) fungicidal 16) and anti-inflammatory 17) activities. Although Ryu et al 18) have reported that cnidicin, a coumarin derivative, inhibited mast cell degranulation, degranulation inhibiting activity of 7-methoxycoumarin has not previously been reported.…”