Differential Effects of Naja naja atra Venom on Immune Activity

Abstract

Previous studies reported that Naja naja atra venom (NNAV) inhibited inflammation and adjuvant arthritis. Here we investigated the role of NNAV in regulation of immune responses in mice. Oral administration of NNAV to normal mice showed significant increase in natural killer cell activity, B lymphocyte proliferation stimulated by lipopolysaccharides, and antibody production in response to sheep red blood cells. Meanwhile, NNAV markedly decreased T lymphocyte proliferation stimulated by concanavalin A, arrested the cell cycle at G0/G1 phase, and suppressed CD4 and CD8 T cell divisions. Furthermore, NNAV inhibited the dinitrofluorobenzene-induced delayed-type hypersensitivity reaction. This modulation of immune responses may be partly attributed to the selective increase in Th1 and Th2 cytokines (IFN-γ, IL-4) secretion and inhibition of Th17 cytokine (IL-17) production. In dexamethasone-induced immunosuppressed mice, NNAV restored the concentration of serum IgG and IgM, while decreasing the percentage of CD4 and CD8 T-cell subsets. These results indicate that NNAV enhances the innate and humoral immune responses while inhibiting CD4 Th17 and CD8 T cell actions, suggesting that NNAV could be a potential therapeutic agent for autoimmune diseases.

Celastrol, a Chinese herbal compound, controls autoimmune inflammation by altering the balance of pathogenic and regulatory T cells in the target organ

“…The above studies highlight the utility of natural products for the treatment of experimental arthritis. Earlier, an extract of Tripterygium wilfordii and its bioactive component triptolide were shown to be effective in the treatment of RA [ 22 ], and snake venom has been shown to suppress adjuvant arthritis [ 23 ], further reinforcing the potential of the vast resource of natural products for the treatment of RA.…”

Venom-based peptide therapy: insights into anti-cancer mechanism

“…In some studies, bee venom is known to the by-pass innate immune system and directly influences T cell activity or adaptive immune system [ 161 , 162 ]. Venom peptides such as cobra venom factor, cobra toxin, PLA2, melittin from snake Naja naja atra were observed to enhance NK cells activity by increasing the production of cell stress signaling protein interferon-g in immune-suppressed mice (IFN-g) [ 163 ]. In the same study, authors have also observed suppression of T cell proliferation especially CD8 T cells through inhibition of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) [ 163 ].…”

“…Venom peptides such as cobra venom factor, cobra toxin, PLA2, melittin from snake Naja naja atra were observed to enhance NK cells activity by increasing the production of cell stress signaling protein interferon-g in immune-suppressed mice (IFN-g) [ 163 ]. In the same study, authors have also observed suppression of T cell proliferation especially CD8 T cells through inhibition of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) [ 163 ]. In contrast, bee venom PLA2 and melittin are reported to increase T cell response by increasing synthesis of cytokines IL-1 and TNF-a on monocytes [ 164 ].…”

Anti-Inflammatory and Immune Regulatory Actions of Naja naja atra Venom

“…Meanwhile, Chen et al reported that the neurotoxin of cobra venom presented analgesic effects through the cholinergic system but not the opioid system [ 9 ]. Interestingly, in recent years, there were several studies showing that Naja naja atra venom (NNAV) had potent anti-inflammation and immune regulation effects [ 10 , 11 ]. NNAV is also effective in relieving symptoms and tissue damage in animal models of RA, SLE, and nephrotic syndrome [ 11 , 12 , 13 ].…”