However, though there are many reports that show that the crude venom or components from Naja Naja atra have analgesic effects, to our knowledge, there is no report on the pharmacological actions of oral administered denatured Naja Naja atra venom (NNAV) in rheumatoid arthritis model. Naja Naja atra (Chinese cobra) and itstoxic components were considered as a medicine in traditionalChinese medicine. We have previously reported that cobratoxin (CTX), the long-chain α-neurotoxin from Thailand cobra venom, had anti-inflammatory and antinociceptive effects on adjuvant arthritis and can relieve the formalin-induced inflammatory pain in rats. Similarly, the anti-arthritic activity of Indian monocellate cobra venom was also verified. Crotalus durissus terrificus venom, which contains crotoxin as a major active component, significantly inhibited edema and migration of polymorphonuclear cells in carrageenan-induced arthritis in mice. In addition, antiarthritis effects of snake venoms have also been reported recently. Some biotoxins, such as bee venom, have been reported to have antiarthritis and pain-relieving activity in a number of literatures. Venom therapy, as complementary and alternative medicine approach, has been used for thousands of years to treat arthritis in folk medicine. Therefore, it is urgent to find candidates for the development of new drugs in RA. However, the current therapies for RA are often unsatisfactory, because of inadequate efficacy or various side effects, including gastrointestinal disorders, immunodeficiency, and humoral disturbances. For the treatment of rheumatoid arthritis, strategies have shifted from controlling symptoms (such as nonsteroidal anti-inflammatory drugs and corticosteroids) to restraint the disease process with the suppression of immune system (the usage of disease-modifying antirheumatic drugs (DMARDs) and biologic agents). B lymphocytes may play a predominant role in the pathogenesis of RA.
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A generally accepted viewis the disorder of the immune system. Although the pathogenesis of RA remains obscure, many pathogenic pathways that are involved in the development of RA have been revealed over the past years. The disease is characterized by pain, swelling, and stiffness of multiple joints.
Rheumatoid arthritis (RA) is a systemic and progressive autoimmune disease, which affects about 0.5–1% of the population worldwide. Although the native NNAV and TWP rendered the similar pharmacological actions on the above four models with less potency than that of the denatured NNAV, these findings demonstrate that oral administration of the denatured NNAV produces antinociceptive and anti-inflammatory activities on rheumatoid arthritis.
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Additionally, the increase in serum TNF- α and the decrease in serum IL-10 in AIA rats were reversed by the denatured NNAV. We found that the denatured NNAV (90, 270 μg/kg) significantly reduced time of licking paw, paw volume, and granuloma weight in above inflammatory models and also attenuated paw edema, mechanical hyperalgesia, and histopathology changes in AIA rats. For adjuvant-induced arthritis (AIA) rats, paw edema, mechanical withdrawal threshold, serum levels of TNF- α and IL-10, and histopathological changes of the affected paw were assessed. We measured time of licking the affected paw in formaldehyde-induced inflammatory model, paw volume in egg-white-induced inflammation, and granuloma weight in formalin-soaked filter paper-induced granuloma.
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Rheumatoid arthritis-associated models, the denatured NNAV (heat treated 30, 90, 270 μg/kg), the native NNAV (untreated with heat 90 μg/kg), and Tripterygium wilfordii polyglycoside (TWP, 15 mg/kg) were administrated orally either prophylactically or therapeutically. To investigate the antinociceptive and anti-inflammatory activities of the denatured Naja Naja atra venom (NNAV) in