当前位置： SCI文献检索 > BRITISH JOURNAL OF PHARMACOLOGY期刊下所有文献 > NCX 2057, a novel NO-releasing derivative of ferulic acid, suppresses inflammatory and nociceptive responses in in vitro and in vivo models.

NCX 2057, a novel NO-releasing derivative of ferulic acid, suppresses inflammatory and nociceptive responses in in vitro and in vivo models.

Abstract：

BACKGROUND AND PURPOSE:We previously reported that NCX 2057, a compound comprising a nitric oxide (NO)-releasing moiety and the natural antioxidant, ferulic acid (FA), inhibits pro-inflammatory mediators through NO-mediated gene regulation. Here, we have assessed the activities of NCX 2057 in models of inflammatory and neuropathic pain, and characterized its effects on cyclooxygenase (COX)-1 and COX-2. EXPERIMENTAL APPROACH:Anti-nociceptive and anti-inflammatory activities of NCX 2057 were measured in vitro and in vivo in models of inflammatory (carrageenan) and neuropathic (chronic constriction injury; CCI) pain. Effects of NCX 2057 were measured on COX-1 and COX-2 activities in RAW 264.7 macrophages. KEY RESULTS:NCX 2057 dose-dependently inhibited single motor unit responses to noxious mechanical stimulation (ID(50)= 100 micromol kg(-1)) and wind-up responses in rats with paw inflammation induced by carrageenan. Moreover, NCX 2057 inhibited allodynic responses following CCI of the sciatic nerve [ipsilateral Paw Withdrawal Threshold (g): vehicle: 41.4 +/- 3.3; NCX 2057: 76.3 +/- 4.8 FA: 37.9 +/- 15.5 at 175 micromol kg(-1)]. NCX 2057 reversed carrageenan-induced hyperalgesic responses in mice and inhibited prostaglandin E(2) formation in paw exudates. Finally, NCX 2057 competitively inhibited COX-1 and COX-2 activities in whole RAW macophages (IC(50)= 14.7 +/- 7.4 and 21.6 +/- 7.5 microM, respectively). None of these properties were exhibited by equivalent treatments with FA or standard NO donor compounds. CONCLUSIONS AND IMPLICATIONS:These studies indicate that NCX 2057 is effective in chronic inflammatory and neuropathic pain models, probably because of its particular combination of anti-COX, antioxidant and NO-releasing properties.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Ronchetti D,Borghi V,Gaitan G,Herrero JF,Impagnatiello F

doi

10.1111/j.1476-5381.2009.00324.x

subject

Has Abstract

pub_date

2009-09-01 00:00:00

pages

569-79

issue

eissn

0007-1188

issn

1476-5381

pii

BPH324

journal_volume

158

pub_type

杂志文章

在线工具

NCX 2057, a novel NO-releasing derivative of ferulic acid, suppresses inflammatory and nociceptive responses in in vitro and in vivo models.