| Research Abstract |
We have previously reported that lignins, prepared from pine cone of Pinus parviflora Sieb. et Zuc. and other trees, inhibited the plaque formation of herpes simplex virus and influenza virus in cultured cells, cytopathic effect induced by rotavirus, enterovirus or human immunodeficiency virus (HIV). These natural lignified materials have heterogeneous polyphenolic structure including polysaccharides, making the identification of active principle(s) difficult. Antiviral activity of lignins was not affected by decomposition of polysaccharide portions by H_2SO_4, but was almost completely destroyed by decomposition of polyphenolic portions by NaClO_2. In order to confirm the importance of the polyphenolic portions for antiviral activity induction, water-soluble synthetic lignins (MW 10-50 kD) were synthesized from p-coumaric acid and caffeic acid in the presence of horseradish peroxidase and H_2O_2, in collaboration with Prof. Yutaka Kawazoe (Nagoya City Univ.). Anti-HIV activity of synt
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hetic lignins (CC_<50>/EC_<50>=100) was superior to that of natural lignin, phenylpropenoid monomers or tannin-related compounds. Sucrose density gradient centrifugation revealed the rapid binding of ^<125>I-labeled synthetic lignin to the infuluenza virus. Synthetic lignin significantly inhibited the binding of HIV to the cultured cells, although its inhibitory effect was lower than that of sulfated polysaccharides. Since synthetic lignin specifically stimulate the iodination (incorporation of ^<125>I into an acid-insoluble fraction) of myeloperoxidase (MPO)-positive cells, the possibility whether anti-HIV effect of synthesis lignins depends on cellular MPO content was tested. This possibility, however, was eliminated by our finding that comparable anti-HIV activity of synthetic lignin was induced in both HL-60 cells (with high MPO content) and U-937 (with low MPO content). This suggests that HOCl, produced by MPO-H_2O_2-halide system, might not play significant role. We found that synthetic lignin scavenge O_2^- and HOCl in vitro, there is a possibility that synthetic lignin might inhibit the HIV expression induced by exposure to such active oxygens. We also found that natural and synthetic lignins and some tannin-related compounds stimulated the production of IL-1 and TNF by human peripheral blood mononuclear cells, the possibility should be tested that synthetic lignin might induce the production of anti-HIV cytokines. Less
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