The Efficacy Of Anti-Rheumatoid Arthritis Actions Of Naja Naja Atra Venom And Underlysing Mechanisms

Objective: To investigate the anti-nociceptive and anti-inflammatory activities by theoral administration of the denatured Naja Naja Atra Venom (NNAV) in rheumatoid arthritismodels.Methods: The denatured NNAV and the undenatured NNAV were analyzed bySDS-PAGE gel electrophoresis. After incubating gel with coomassie brilliant blue stainingR250for2h, gel was eluted with bleaching solution overnight. The proteins signal wasread with an Odyssey Western Blot Analysis system. Three inflammatory models wereinduced by the injection of formaldehyde and egg white, implantation offormaldehyde-soaked filter papers. Rheumatoid arthritis model was induced by theinjection of Complete Freund’s Adjuvant (CFA). The denatured NNAV (heat-treated;30,90,270μg/kg), the undenatured NNAV (untreated with heat;90μg/kg) and TripterygiumWilfordii Polyglycoside (TWP,15mg/kg), were administrated orally eitherprophylactically or therapeutically. Time of licking the affected paw in formaldehyde-induced inflammatory model, paw volume in egg white-induced inflammation andgranuloma weight in formalin-soaked filter paper-induced granuloma were measured. Foradjuvant-arthritis (AA), paw edema, ankle joint edema, mechanical withdrawal threshold,serum levels of TNF-α and IL-10and histopathological changes of the affected paw wereassessed.Results: Heat-treatment slightly reduced high molecular weight proteins and reducedprotein smears between7-20KD. The most robust change was the increasing in theintensity of protein band with molecular weight7KD in the denatured NNAV. Thedenatured NNAV (90,270μg/kg) significantly reduced time of paw licking, paw volumeand granuloma weight in three inflammatory models. In AA rats it could also attenuate pawedema, ankle joint edema, mechanical hyperalgesia and histopathology changes includingaccumulation of collagen and hyperplasia of the articular cartridge and synovium. Inaddition, the increase in serum TNF-α and the decrease in serum IL-10in AA rats were reversed by the denatured NNAV. Although the undenatured NNAV (90μg/kg) and TWP(15mg/kg) rendered the similar pharmacological actions on the above four models withless potency than that the denatured NNAV.Conclusion: Oral administration of the denatured NNAV produced anti-nociceptiveand anti-inflammatory activities in rodents, and thus may be a novel strategy for treatmentof RA.