A novel synthetic, nonpsychoactive cannabinoid acid (HU‐320) with antiinflammatory properties in murine collagen‐induced arthritis

A novel synthetic, nonpsychoactive cannabinoid acid (HU‐320) with antiinflammatory properties... Objective To explore the antiarthritic potential of a novel synthetic cannabinoid acid, Hebrew University–320 (HU‐320), in the DBA/1 mouse model of arthritis, and to investigate in vitro antiinflammatory and immunosuppressive effects of HU‐320 on macrophages and lymphocytes. Methods DBA/1 mice were immunized with bovine type II collagen (CII) to induce arthritis and then injected intraperitoneally daily with HU‐320. The effects of treatment on arthritic changes in hind feet were assessed clinically and histologically, and draining lymph node responses to CII were assayed. Murine splenic and human blood lymphocytes were cultured to study the effect of HU‐320 on polyclonal mitogenic stimulation. Macrophage cultures were set up to evaluate in vitro effects of HU‐320 on production of tumor necrosis factor α (TNFα) and reactive oxygen intermediates (ROIs). The effect of HU‐320 administration on lipopolysaccharide‐induced serum TNF levels was assayed using C57BL/6 mice. Bioactive TNF production was measured using BALB/c clone 7 target cells. Evaluation of HU‐320 psychoactivity was performed using established laboratory tests on Sabra mice. Results Systemic daily administration of 1 and 2 mg/kg HU‐320 ameliorated established CII‐induced arthritis. Hind foot joints of treated mice were protected from pathologic damage. CII‐specific and polyclonal responses of murine and human lymphocytes were down‐modulated. HU‐320 inhibited production of TNF from mouse macrophages and of ROIs from RAW 264.7 cells and suppressed the rise in serum TNF level following endotoxin challenge. HU‐320 administration yielded no adverse psychotropic effects in mice. Conclusion Our studies show that the novel synthetic cannabinoid acid HU‐320 has strong antiinflammatory and immunosuppressive properties while demonstrating no psychoactive effects. The profound suppressive effects on cellular immune responses and on the production of proinflammatory mediators all indicate its usefulness as a novel nonpsychoactive, synthetic antiinflammatory product. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Arthritis & Rheumatology Wiley

A novel synthetic, nonpsychoactive cannabinoid acid (HU‐320) with antiinflammatory properties in murine collagen‐induced arthritis

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Publisher
Wiley
Copyright
Copyright © 2004 by the American College of Rheumatology
ISSN
0004-3591
eISSN
1529-0131
D.O.I.
10.1002/art.20050
Publisher site
See Article on Publisher Site

Abstract

Objective To explore the antiarthritic potential of a novel synthetic cannabinoid acid, Hebrew University–320 (HU‐320), in the DBA/1 mouse model of arthritis, and to investigate in vitro antiinflammatory and immunosuppressive effects of HU‐320 on macrophages and lymphocytes. Methods DBA/1 mice were immunized with bovine type II collagen (CII) to induce arthritis and then injected intraperitoneally daily with HU‐320. The effects of treatment on arthritic changes in hind feet were assessed clinically and histologically, and draining lymph node responses to CII were assayed. Murine splenic and human blood lymphocytes were cultured to study the effect of HU‐320 on polyclonal mitogenic stimulation. Macrophage cultures were set up to evaluate in vitro effects of HU‐320 on production of tumor necrosis factor α (TNFα) and reactive oxygen intermediates (ROIs). The effect of HU‐320 administration on lipopolysaccharide‐induced serum TNF levels was assayed using C57BL/6 mice. Bioactive TNF production was measured using BALB/c clone 7 target cells. Evaluation of HU‐320 psychoactivity was performed using established laboratory tests on Sabra mice. Results Systemic daily administration of 1 and 2 mg/kg HU‐320 ameliorated established CII‐induced arthritis. Hind foot joints of treated mice were protected from pathologic damage. CII‐specific and polyclonal responses of murine and human lymphocytes were down‐modulated. HU‐320 inhibited production of TNF from mouse macrophages and of ROIs from RAW 264.7 cells and suppressed the rise in serum TNF level following endotoxin challenge. HU‐320 administration yielded no adverse psychotropic effects in mice. Conclusion Our studies show that the novel synthetic cannabinoid acid HU‐320 has strong antiinflammatory and immunosuppressive properties while demonstrating no psychoactive effects. The profound suppressive effects on cellular immune responses and on the production of proinflammatory mediators all indicate its usefulness as a novel nonpsychoactive, synthetic antiinflammatory product.

Journal

Arthritis & RheumatologyWiley

Published: Mar 1, 2004

References

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  • Relationship between Th1/Th2 cytokine patterns and the arthritogenic response in collagen‐induced arthritis
    Mauri, Mauri; Williams, Williams; Walmsley, Walmsley; Feldmann, Feldmann
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    Mechoulam, Mechoulam; Parker, Parker; Gallily, Gallily
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    Zuardi, Zuardi; Morais, Morais; Guimaraes, Guimaraes; Mechoulam, Mechoulam
  • Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide
    Bisogno, Bisogno; Hanus, Hanus; De Petrocellis, De Petrocellis; Tchilibon, Tchilibon; Ponde, Ponde; Brandi, Brandi
  • Blockade of IL‐12 during the induction of collagen‐induced arthritis (CIA) markedly attenuates the severity of the arthritis
    Malfait, Malfait; Butler, Butler; Presky, Presky; Maini, Maini; Brennan, Brennan; Feldmann, Feldmann
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  • Dimethylheptyl‐THC‐11 oic acid: a nonpsychoactive antiinflammatory agent with a cannabinoid template structure
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