Abstract
Bee venom (BV) is widely used as a traditional China medicine to treat various conditions, including rheumatoid arthritis (RA). The aim of the present study was to evaluate the effects of systemic BV (60 mg/kg) as an anti-arthritic natural product, compare it with Methotrexate and determine the possible underlying mechanisms of BV action using complete Freund's adjuvant-induced arthritic rats. The development of signs of RA signs (knee joint circumference and arthritis scoring index) was evaluated. Erythrocyte sedimentation rate, serum tumor necrosis factor-α (TNF-α) and serum interleukin-1β (IL-1β) levels were measured at the end of the study. Histopathological examination followed by immunostaining of NF-κB (P65) was performed on the affected knee joints. Additionally, in vitro cyclooxygenase (COX) inhibition activity, carrageenan paw edema test and acetic acid writhing tests were performed to evaluate the anti-inflammatory and analgesic effects of the assessed dose and compared with diclofenac. An acute toxicity test was performed to establish the safety of BV at high doses. The results of the present study highlighted the potential of systemic BV on preventing the development of signs of RA. BV also significantly reduced serum levels of TNF-α, IL-1β and NF-κB in the affected joints. In addition to its potent analgesic activity, BV exhibited favorable inhibitory activity of the COX pathway in both in vivo and in vitro models. Therefore, high dose administration of systemic BV displayed safe and promising anti-arthritic, anti-inflammatory and analgesic properties through regulation of different mechanisms associated with the pathogenesis of RA.