Elsevier

Biochemical Pharmacology

Volume 36, Issue 4, 15 February 1987, Pages 469-474
Biochemical Pharmacology

Selective inhibition of collagen accumulation by N-(3, 4-dimethoxycinnamoyl)anthranilic acid (N-5') in granulation tissue

https://doi.org/10.1016/0006-2952(87)90353-4Get rights and content

Abstract

The effect of topically applied N-5', an inhibitor of chemical mediator release from mast cells, on the carrageenin-air-pouch inflammation was studied. The formation of granulation tissue, the accumulation of exudate and the number of infiltrating cells were significantly reduced by the treatment with N-5' (100 mg/kg).

The collagen content in granulation tissue was dose-dependently reduced without affecting the noncollagen protein and DNA content by treatment with N-5'. At a dose of 100 mg/kg of N-5', prolyl hydroxylase activity in the tissue was significantly decreased. The selective inhibition of collagen accumulation in granulation tissue resulted from reduction of collagen biosynthesis in vivo.

N-5' did not directly inhibit collagen synthesis by diploid fibroblasts, but inhibited fibroblast proliferation in culture. Such results indicate that one of the inhibitory mechanisms of collagen accumulation by N-5' in inflamed sites may involve the inhibition of fibroblast proliferation.

References (25)

  • J.M. Seyer

    Fundam. appl. Toxicol.

    (1976)
  • O.H. Lowry et al.

    J. biol. Chem.

    (1951)
  • K.W. Giles et al.

    Nature, Lond.

    (1965)
  • B. Peterkofsky et al.

    Biochemistry

    (1971)
  • J. Uitto et al.

    J. Invest. Dermat.

    (1979)
  • D.J. Prockop et al.

    New Eng. J. Med.

    (1979)
    D.J. Prockop et al.

    New Eng. J. Med.

    (1979)
  • R. Pérez-Tamayo

    Am. J. Pathol.

    (1978)
  • A. Hatamochi et al.

    Arch. Dermatol. Res.

    (1985)
  • J.R. Boucek

    Otolaryng, Clin, North America.

    (1984)
  • T.L. Whiteside et al.

    J. Lab. clin. Med.

    (1984)
  • P.H. Hart et al.

    Scand. J. Immunol.

    (1983)
  • R.L. Johnson et al.

    J. clin. Invest.

    (1976)
  • Cited by (76)

    • Inflammation, immunity and potential target therapy of SARS-COV-2: A total scale analysis review

      2021, Food and Chemical Toxicology
      Citation Excerpt :

      It is a potent inhibitor of NLRP3 which is an inflammasome that drives inflammation in many disorders including bronchial asthma (Huang et al., 2018) (Fig. 1B). Tranilast represses fibrosis by inhibition of fibroblast activity (Isaji et al., 1987) and collagen formation via reducing the activity of TGF-β (Suzawa et al., 1992). It has been proved that it mitigates the pulmonary fibrosis in experimental animals (Mori et al., 1995).

    • TRPV2 channel inhibitors attenuate fibroblast differentiation and contraction mediated by keratinocyte-derived TGF-β1 in an in vitro wound healing model of rats

      2018, Journal of Dermatological Science
      Citation Excerpt :

      Therefore, we considered that TRPV2 may be involved in the contraction of the collagen gel. Tranilast has been used clinically to improve keloid and hypertrophic scars because of its inhibition of collagen accumulation in granulation tissue [26]. Tranilast was shown to inhibit the release of TGF-β1 from keloid fibroblasts, but not from healthy skin fibroblasts, and to suppress collagen synthesis in keloid fibroblasts [27].

    • Determination of tranilast in bio-samples by LC–MS/MS: Application to a pharmacokinetic and brain tissue distribution study in rats

      2018, Journal of Pharmaceutical and Biomedical Analysis
      Citation Excerpt :

      Tranilast (Fig. 1A), [N-(3,4-dimethoxycinnamoyl) anthranilic acid, as an anti-allergic drug used clinically for the treatment of bronchial asthma, atopic dermatitis, allergic conjunctivitis, keloid and hypertrophic scar [1–9], has been subsequently identified as a potent drug for the nervous system disorder [10].

    • Protective effects of tranilast on experimental colitis in rats

      2017, Biomedicine and Pharmacotherapy
      Citation Excerpt :

      Tranilast (TL), N-(3,4-dimethoxycinnamoyl) anthranilic acid, has been shown to have anti-inflammatory and anti-allergic effects and inhibit the release of inflammatory mediators from mast cells and basophils [9,10]; thus, TL is clinically used for treating bronchial asthma, atopic rhinitis, and atopic dermatitis [11]. Other suppressive effects of TL have also been reported, including collagen synthesis [12], the action of transforming growth factor beta (TGF-β) [13,14], and the production of TNF-α [15], and TL is expected to show therapeutic potential against fibrotic diseases and cancer. According to a case report, the oral administration of TL (300 mg/day) to a female CD patient improved inflammatory symptoms, maintained long-term remission, and prevented the relapse of bowel inflammation [16].

    View all citing articles on Scopus
    View full text