Abstract
Cardiotoxin (CTX) from Naja naja atra venom (NNAV) reportedly had analgesic effect in animal models but its role in inflammation and arthritis was unknown. In this study, we investigated the analgesic, anti-inflammatory, and antiarthritic actions of orally administered CTX-IV isolated from NNAV on rodent models of inflammation and adjuvant arthritis. CTX had significant anti-inflammatory effects in models of egg white induced nonspecific inflammation, filter paper induced rat granuloma formation, and capillary osmosis tests. CTX significantly reduced the swelling of paw induced by egg white, the inflammatory exudation, and the formation of granulomas. CTX reduced the swelling of paw, the AA clinical scores, and pathological alterations of joint. CTX significantly decreased the number of the CD4 T cells and inhibited the expression of relevant proinflammatory cytokines IL-17 and IL-6. CTX significantly inhibited the secretion of proinflammatory cytokine IL-6 and reduced the level of p-STAT3 in FLS. These results suggest that CTX inhibits inflammation and inflammatory pain and adjuvant-induced arthritis. CTX may be a novel therapeutic drug for treatment of arthritis.
Highlights
Rheumatoid arthritis (RA) is a systemic and progressive autoimmune disease characterized by joint inflammation, pain, cartilage, and bone destruction, which affects about 0.5–1% of population worldwide
We investigated if orally administrated CTX could produce analgesic, anti-inflammatory, and antiarthritic effects in animal models
In the acetic acid writhing assay, pretreatment with CTX (30, 180 μg/kg) or aspirin significantly reduced number of writhes (Figure 1(b)). These results suggest that oral CTX has an analgesic effect
Summary
Rheumatoid arthritis (RA) is a systemic and progressive autoimmune disease characterized by joint inflammation, pain, cartilage, and bone destruction, which affects about 0.5–1% of population worldwide. The existing drugs to treat RA include nonsteroidal anti-inflammatory drugs, corticosteroids, disease-modifying antirheumatic drugs (DMARDs), and monoclonal antibodies [1]. These drugs are often associated with various side effects and high cost [2]. Deviation from our general idea, it was reported that oral administration of a low molecular weight component from Crotalus durissus venom and a neurotoxin from king cobra venom both produced analgesic effects [11, 12]. Oral administration of denatured NNAV exerted analgesic and anti-inflammatory effects in arthritis models [13]. We speculate that oral administration of CTX might produce pharmacological effects in an adjuvant animal model of rheumatoid arthritis
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