Study of a lipid extract from Eryx snakes in rat adjuvant-induced arthritis under a therapeutic regimen: comparison with methotrexate and leflunomide
摘要
Inflammation-driven joint pathology remains a major cause of disability, motivating the search for safe multi-target therapies. We investigated the anti-inflammatory efficacy and tolerability of a lipid extract of Eryx snakes (LEES) in the rat model of adjuvant-induced arthritis (complete Freund’s adjuvant). Arthritic rats received once-daily oral treatment from day 15 to day 30 with LEES (50 mg/kg) and were compared with reference drugs (methotrexate 0.05 mg/kg; leflunomide 5 mg/kg) and vehicle controls. Outcomes included paw volume (plethysmometry), local skin temperature (infrared thermometry), and mechanical pain threshold (plantar aesthesiometry); systemic effects were assessed by serum cytokine - interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-α) - complete blood counts, and histology of joint, liver and spleen. LEES attenuated paw edema and local hyperthermia, increased the mechanical pain threshold, and exerted immunomodulatory effects by regulating the circulating cytokine profile (lowering IL-6 and TNF-α with higher IL-10). Notably, LEES was superior to leflunomide in reducing paw edema and performed comparably to both reference drugs across other key efficacy endpoints. Semi-quantitative histological scoring confirmed that LEES effectively limited articular structural damage without inducing the hepato-splenic toxicity associated with methotrexate. These findings indicate that LEES possesses multimodal immunomodulatory and analgesic actions with a highly favorable tolerability profile, supporting its further preclinical development as a potential adjunct or alternative to existing therapies.