Effect of galantamine on adjuvant-induced arthritis in rats

Stimulation of the vagus nerve suppresses cytokine production and macrophage activation, via the interaction of its neurotransmitter acetylcholine (ACh) with the alpha 7 subunit of the nicotinic acetylcholine receptor (alpha 7nAChR), present on neurons and inflammatory cells. The present study aimed to verify the potential anti-inflammatory effect of galantamine against experimental arthritis induced in rats. fourteen days post adjuvant injection, Sprague-Dawley rats were treated orally with three doses of galantamine (1.25, 2.5 and 5 mg/kg) or leflunomide (10 mg/kg) for 2 weeks and arthritis progression was assessed by hind paw swelling. Additionally, serum biomarkers, viz., anti-cyclic citrullinated peptide antibodies (Anti-CCP), tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10) and monocyte chemoattractant protein-1 (MCP-1) were measured. Radiological examination of the hind paws was also carried out to evaluate the degree of joint damage. Adjuvant arthritis led to a significant weight loss, marked swelling of the hind paw and alteration in the serum levels of anti-CCP, INF-alpha, IL-10 and MCP-1. These alterations were associated with significant radiological changes of the joints. Galantamine, in a close-dependent manner, reduced significantly all biomarkers of inflammation, with the highest dose showing the best beneficial anti-inflammatory effect that was superior in magnitude to the reference drug leflunomide in most of the studied parameters. In conclusion, these results suggest that galantamine may represent a novel, inexpensive and effective therapeutic strategy in the treatment of rheumatoid arthritis. (C) 2015 Elsevier B.V. All rights reserved.