Cobrotoxin extracted from Naja atra venom relieves arthritis symptoms through anti-inflammation and immunosuppression effects in rat arthritis model

J Ethnopharmacol. 2016 Dec 24;194:1087-1095. doi: 10.1016/j.jep.2016.11.009. Epub 2016 Nov 10.


Ethnopharmacological relevance: The Naja atra (Chinese cobra), primarily distributing in the low or medium altitude areas of southern China and Taiwan, was considered as a medicine in traditional Chinese medicine and used to treat pain, inflammation and arthritis.

Aim of the study: To study the anti-inflammatory and anti-arthritic activities of cobrotoxin (CTX), an active component of the venom from Naja atra.

Materials and methods: Adjuvant-induced arthritis (AA) rats were used as the animal model of rheumatoid arthritis. The anti-arthritic effects of CTX were evaluated through the arthritis score, paw edema and histopathology changes of joints. The anti-inflammation effects were assayed by the level of IL-6, TNF-α, IL-1β and the number of inflammatory cells in peripheral blood, as well as the proliferation of fibroblast-like synoviocytes (FLS). The immune level was valued by the proliferation of T cells and the level of CD4 and CD8.

Results: CTX alleviated the disease development of AA rats according to the ameliorating arthritis score, paw edema and histopathology character. At the meanwhile, CTX decreased the levels of IL-6, TNF-α, IL-1β and the numbers of inflammatory cells in peripheral blood. CTX also suppressed the abnormal increasing of CD4+ T cells/ CD8+ T cells ratio, and could significantly inhibit T cell proliferation. Consistent with its effects on inhibiting granuloma's formation, CTX inhibited the proliferation of the cultured FLSs. Further studies on inflammatory signaling in FLSs revealed that CTX could inhibit the NF-κB signaling pathway.

Conclusions: CTX has beneficial effects on rheumatoid arthritis by its immune regulation effects and anti-inflammation effects. The inhibition of NF-κB pathway partly contributes to the anti-inflammatory properties of CTX.

Keywords: Anti-inflammation; Cobrotoxin; Fibroblast-like synoviocytes; NF-κB; Rheumatoid arthritis.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Arthritis, Experimental / drug therapy
  • Arthritis, Rheumatoid / drug therapy*
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Proliferation / drug effects
  • Cobra Neurotoxin Proteins / chemistry*
  • Cobra Neurotoxin Proteins / pharmacology*
  • Disease Models, Animal
  • Edema / drug therapy
  • Edema / metabolism
  • Elapid Venoms / chemistry*
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Immunosuppression Therapy / methods
  • Immunosuppressive Agents / pharmacology*
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Male
  • Mice
  • Mice, Inbred ICR
  • NF-kappa B / metabolism
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects
  • Synovial Membrane / drug effects
  • Tumor Necrosis Factor-alpha / metabolism


  • Anti-Inflammatory Agents
  • Cobra Neurotoxin Proteins
  • Elapid Venoms
  • Immunosuppressive Agents
  • Interleukin-1beta
  • Interleukin-6
  • NF-kappa B
  • Tumor Necrosis Factor-alpha