Anti-inflammatory effects of Neurotoxin-Nna, a peptide separated from the venom of Naja naja atra

BMC Complementary and Alternative Medicine

Jianyou Guo¹  Shuijuan Zhang²  Bingbing Zhang²  Li Yao²  Yeping Ruan² 

[1] Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, 100101, P.R China;College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, P.R China

关键词: Nuclear factor kappa B;    Interleukin 1 beta;    Tumor necrosis factor alpha;    Antinociceptive;    Anti-inflammatory;    Neurotoxin-Nna;   

Others  :  1230106
DOI  :  10.1186/1472-6882-13-86

 received in 2012-11-25, accepted in 2013-03-11,  发布年份 2013

【 摘 要 】

Background

Neurotoxin-Nna (NT), an analgesic peptide separated from the venom of Naja naja atra, has reported to have an exceptional specificity to block transmission of the nerve impulse by binding to the α- subunit of the nicotinic acetylcholine receptor in the membrane. However, little information is available on the anti-inflammatory effects of NT. Therefore, the anti-inflammatory activity of Neurotoxin-Nna was investigated in this study.

Methods

The anti-inflammatory effects of NT were evaluated by measuring its influence on several crucial factors in inflammatory pathways, including total antioxidant activity, antinociceptive effects in vivo, nuclear factor kappa B (NF-κB), polymorphonuclear cells (PMN), inducible nitric oxide synthase (iNOS), adhesion molecule (ICAM-1) and tactile hyperalgesia.

Results

NT treatment decreased the levels of tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β). NT treatment decreased the total antioxidant status (TAOS) and reduced CFA-induced tactile hyperalgesia in a dose-dependent manner. NT significantly inhibited regulation of NF-kappaB activation and the production of IL-1β, TNF-α, iNOS and CAM-1. Moreover, NT suppressed infiltration of PMN.

Conclusions

Our results showed that NT reduced CFA-induced tactile hyperalgesia through inhibition inflammatory pathways in experimental inflammatory rats.

【 授权许可】

   
2013 Ruan et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Cura JE, Blanzaco DP, Brisson C, Cura MA, Cabrol R, Larrateguy L, Mendez C, Sechi JC, Silveira JS, Theiller E, de Roodt AR, Vidal JC: Phase I and pharmacokinetics studyof crotoxin (cytotoxic PLA(2), NSC-624244) in patients with advanced cancer. Clin Cancer Res 2002, 8:1033-1041.
• [2]Zhang HL, Han R, Chen ZX, Chen BW, Gu ZL, Reid PF, Raymond LN, Qin ZH: Opiate and acetylcholine-independent analgesic actions of crotoxin isolated from crotalus durissus terrificus venom. Toxicon 2006, 48:175-182.
• [3]Tsetlin V: Snake venom alpha-Neurotoxins and other ‘three-finger’ proteins. Eur J Biochem 1999, 264:281-286.
• [4]Qiumin L, Qingxiong M, Dongsheng L, Shaowen Z, Yonghong J, Yuliang X, Wanyu W: Comparative study of three short-chain Neurotoxins from the venom of Naja kaouthia (Yunnan, China). J Nat Toxins 2002, 11:221-229.
• [5]Tu AT: Neurotoxins of animal venoms: snakes. Ann Rev Biochem 1973, 42:235-238.
• [6]Yang CC: Chemistry and evolution of toxins in snake venom. Toxicon 1974, 12:1-43.
• [7]Rang HP: Acetylcholine receptors. Q Rev Biophys 1975, 7:283-299.
• [8]Marchand F, Perretti M, McMahon SB: Role of the immune system in chronic pain. Nat Rev Neurosci 2005, 6:521-532.
• [9]Han CC, Wei H, Guo J: Anti-inflammatory effects of fermented and non-fermented Sophora flavescens: a comparative study. BMC Complement Altern Med 2011, 11:100. BioMed Central Full Text
• [10]Liu Z, Li P, Zhao D, Tang H, Guo J: Anti-inflammation effects of Cordyceps sinensis mycelium in focal cerebral ischemic injury rats. Inflammation 2011, 34:639-644.
• [11]Laight DW, Gunnarsson PT, Kaw AV, Carrier MJ: Physiological microassay of plasma total antioxidant status in a model of endothelial dysfunction in the rat following experimental oxidant stress in vivo. Environ Toxicol Pharmacol 1999, 7:27-31.
• [12]Yuan XY, Liu W, Zhang P, Wang RY, Guo JY: Effects and mechanisms of aloperine on 2, 4-dinitrofluorobenzene-induced allergic contact dermatitis in BALB/c mice. Eur J Pharmacol 2010, 629:147-152.
• [13]Lu J, Zhang HL, Yin ZZ, Tu Y, Li ZG, Zhao BX, Guo JY: Moxibustion attenuates inflammatory response to chronic exhaustive exercise in rats. Int J Sports Med 2012, 33:580-585.
• [14]Abraham E: NF-kappaB activation. Crit Care Med 2000, 28:100-104.
• [15]Ugusman A, Zakaria Z, Hui CK, Nordin NA: Piper sarmentosum inhibits ICAM-1 and Nox4 gene expression in oxidative stress-induced human umbilical vein endothelial cells. BMC Complement Altern Med 2011, 11:31. BioMed Central Full Text
• [16]Clancy RM, Amin AR, Abramson SB: The role of nitric oxide in inflammation and immunity. Arthritis Rheum 1998, 41:1141-1151.
• [17]Yaren H, Mollaoglu H, Kurt B, Korkmaz A, Oter S, Topal T, Karayilanoglu T: Lung toxicity of nitrogen mustard may be mediated by nitric oxide and peroxynitrite in rats. Res Vet Sci 2007, 83:116-122.
• [18]Ma QP, Woolf CJ: Progressive tactile hypersensitivity: an inflammation induced incremental increase in the excitability of the spinal cord. Pain 1996, 67:97-106.