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Mechanism of antiviral action induced by newly synthesized lignins which have anti-human immunodeficiency virus activity

Research Project

Project/Area Number 03807149
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionShowa University

Principal Investigator

SAKAGAMI Hiroshi  Showa University, School of Medicine, ASSIST. PROF., 医学部, 講師 (50138484)

Project Period (FY) 1991 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1992: ¥600,000 (Direct Cost: ¥600,000)
KeywordsLignin / Phenylpropenoid / Synthesis / Antiviral activity / HIV / Mechanism / Active oxygen / Cytokine / フェニルプロパノイド / 合成リグニン / 抗ウイルス剤 / インフルエンザウイルス / 不活化 / ラジカル
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 … More 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

Report

(3 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Hideki Nakashima et al.: "Lignified materials as medicinal resources.V.Anti-HIV(human immunodeficiency virus)activity of some synthetic lignins" Chem.Pharm.Bull.40. 2102-2105 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hiroshi Sakagami et al.: "Anti-influenza virus activity of a lignin fraction from cone of Pinus parviflora Sieb.et Zucc." In Vivo. 6. 491-496 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hiroshi Sakagami et al.: "Stimulation of human monocyte and polymorpho-nuclear cell iodination and interleukin-1 production by epigallocatechin gallate" Journal of Leukocyte Biology. 51. 478-483 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hiroshi Sakagami et al.: "Lignified materials as a potential medicinal resource.IV.Dehydrogenation polymers of some phenylpropenoides and their capacity" Chem.Pharm.Bull.39. 950-955 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hiroshi Harada et al.: "Possible involvement of lignin structure in anti-influenza virus activity" Antiviral Research. 15. 41-50 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hiroshi Sakagami et al.: "Antitumor,antiviral and immunopotentiating activities of pine cone extracts:Potential medicinal efficacy of natural and synthetic" Anticancer Research. 11. 881-888 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hiroshi Sakagami et al.: "Multiple immunological functions of extracts from the cone of Japanese white pine,Pinus parviflora Sieb.et Zucc." Plenum Press,New York(Edited by H.Friedman et al.), 5 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hideki Nakashima et al: "Lignified materials as medicinal resources. V. Anti-HIV (human immuno deficiency virus) activity of some synthetic lignins." Chem. Pharm. Bull. 40. 2102-2105 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hiroshi Sakagami et al: "Anti-influenza virus activity of a lignin fraction from cone of pinus parviflora Sieb. et Zucc." In Vivo. 6. 491-496 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hiroshi Sakagami et al: "Stimulation of human monocyte and polymorphonuclear cell iodination and interleukin-l production by epigallocatechin gallate" J. Leukocyte Biol. 51. 478-483 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hiroshi Sakagami et al: "Lignified materials as a potential medicinal resource. IV Dehydrogenation polymers of some phenyl- propenoids and their capacity" Chem. Pharm. Bull.39. 950-955 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hiroshi Harada et al: "Possible involvement of lignin structure in anti-influenza virus activity" Antiviral Res. 15. 41-50 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hiroshi Sakagami et al: "Antitumor, antiviral and immunopotentiating activities of pine cone extracts : Potential medicinal efficacy of natural and synthetic lignin-related materials (Review)" Anticancer Res. 11. 881-888 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hiroshi Sakagami et al: Plenum Press, NY Microbial infections (Edited by H. Friedman et al.,). Multiple immuno- logical functions of extracts from the cone of Japanese white pine, Pinus parviflora Sieb. et Zucc., 331-335 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hiroshi Sakagami et al.: "0_2^- scavenging activity of lignins,tannins and PSK" Anticancer Research. 12. (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Hiroshi Sakagami et al.: "Anti-influenza virus activity of a lignin fraction from cone of Pinus parviflora Sieb.et Zucc" In Vivo. 6. 491-496 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Hideki Nakashima et al.: "Lignified materials as medicinal resources.V.Anti-HIV(human immunodeficiency virus) activity of some synthetic lignins" Chem.Pnarm.Bull.40. 2102-2105 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Hiroshi Sakagami et al.: "Stimulation of human monocyte and polymorphonuclear cell iodination and interleukin-1 production by epigallocatechin gallate" Journal of Leukocyte Biology. 51. 478-483 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Hiroshi Sakagami et al.: "Stimulation of monocyte iodination and IL-1 production by tannins and related compounds" Anticancer Research. 12. 377-388 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Hiroshi Sakagami et al.: "Effect of pine seed shell extract on microbial and viral infection" In Vivo. 6. 13-16 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Hiroshi Sakagami et al.: "Multiple immunological functions of extracts from the cone of Japanese white pine,Pinus parviflora Sieb.et Zucc." Plenum Press,New York(Edited by H.Friedman et al.)Title:Microbial infections, 5 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Hiroshi Sakagami ら: "Antiーinfluenza virus activity of synthetically polymerized phenylpropenoids" Biochem.Biophys.Res.Commun. 172. 1267-1272 (1990)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hiroshi Harada ら: "possible involvement of lignin structure in antiinfluenza virus activity" Antiviral Res.15. 41-50 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hiroshi Sakagami ら: "Lignified materials as a potential medicinal resources.IV.Dehydrogenation polymers of some phentlpropenoids and their capacity to stimulate polymorphonuclear cell" Chem.Pharm.Bull.39. 950-955 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hiroshi Sakagami ら: "Antitumor,antiviral and immunopotentiating activities of pine cone extracts:Potential medicinal efficacy of natural abd synthetic ligninーrelated materials(Review)." Anticancer Res.11. 881-888 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hideki Takayama ら: "Inhibition of human immunodeficiency virus forward and reverse transcription by PC6,a natural product from cones of pine trees." AIDS Res.Human Retroviruses. 7. 349-357 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hiroshi Sakagami ら: "Effect of pine seed shell extract on microbial and viral infection" In Vivo. 6. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] 坂上 宏: "リグニン,タンニン類の作用(フリ-ラジカルと和漢薬,奥田拓男,吉川敏一編集の第3章)" 国際医書出版, 9 (1990)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hiroshi sakagami: "Multiple immunological functions of extracts from the cone of Japanese white pine,Pinus parviflora Sieb.et Zucc.(Microbial infections;Role of BRMs,edited by H.Friodman and T.W.Klein)" Plenum Publishing Corporation, 4 (1992)

    • Related Report
      1991 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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