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

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 ␣ (TNF␣) 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.

Evaluation of the anti-inflammatory, anti-catabolic and pro-anabolic effects of E-caryophyllene, myrcene and limonene in a cell model of osteoarthritis

“…juresianum, is completely inactive. This finding is somewhat unexpected as E-caryophyllene has been reported to exert anti-inflammatory effects by activating cannabinoid CB2 receptors (Bento et al, 2011;Medeiros et al, 2007) and endogenous and synthetic cannabinoids have been reported to decrease inflammation in animal models of arthritis (Sumariwalla et al, 2004) and to inhibit IL-1-induced NO production in bovine chondrocytes (Mbvundula et al, 2005).…”

Cannabinoids, Endocannabinoids, and Related Analogs in Inflammation

“…1) is usually the most abundant nonpsychoactive cannabinoid in the plant, and it and analogs of CBD have been studied more extensively in recent years. Thus, CBD reduces joint inflammation in collagen-induced arthritis (CIA) in mice (11) and carrageenan paw edema in rats (12). CBD treatment also suppressed release of tumor necrosis factor (TNF)α from synovial cells isolated from the mice.…”

Rapid-onset clinical and mechanistic effects of anti-C5aR treatment in the mouse collagen-induced arthritis model

“…The effect of treatment on infiltration of inflammatory cells known to express C5aR into the paws was investigated by immunohistochemistry on the most severely affected paw from each mouse in the anti-mC5aR-treated group and its isotype control group [34]. Macrophages were detected with anti-F4/80 and neutrophils with anti-Ly6B.2, and the analyses were quantified by digitalized image analysis.…”