Attenuation of neuropathic pain and neuroinflammatory responses by a pyranocoumarin derivative, anomalin in animal and cellular models

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• 作者：Salman Khan^a ; ^b ; ^c ; ^{skhan@qau.edu.pk" class="auth_mail" title="E-mail the corresponding author} ; Ran Joo Choi^c ; ^d ; Joohee Lee^c ; Yeong Shik Kim^c ; ^{kims@snu.ac.kr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Neuropathic pain ; Anti-neuroinflammation ; STZ-induced diabetic type I ; Anomalin ; N2a cells
• 刊名：European Journal of Pharmacology
• 出版年：2016
• 出版时间：5 March 2016
• 年：2016
• 卷：774
• 期：Complete
• 页码：95-104
• 全文大小：1561 K

文摘

The present study investigated the neuropathic pain, anti-neuroinflammatory and neuroprotective properties of a pyranocoumarin derivative (anomalin) in in vivo and in vitro models. An in vivo streptozotocin (STZ)-induced diabetic neuropathic pain model demonstrated that anomalin significantly suppressed neuropathic pain in mice. To identify the molecular mechanism of the anti-neuropathic pain activity of anomalin, sodium-nitroprusside (SNP)-induced neuroinflammation in neuro-2a (N2a) cells was further investigated in signaling pathways. The effects of anomalin against SNP-induced toxicity, nitrite production and related mRNA gene expression (iNOS and COX-2) were considerably reduced by anomalin in the SNP-induced N2a cells. In the molecular signaling pathway, anomalin effectively blocked the SNP-induced activation of the IKKα/β, IκBα, ERK1/2 and p38 MAPK pathways. Furthermore, anomalin remarkably reduced the increase in the SNP-induced nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway. Additionally, the pro-inflammatory cytokines level was remarkably inhibited by anomalin in high glucose-induced DRG primary neurons and SNP-induced N2a cells. These findings indicate that anomalin has anti-neuropathic pain, anti-neuroinflammatory and neuroprotective effects against STZ-induced diabetic type I neuropathic pain and SNP-induced in neuronal cell models via the inactivation of the NF-κB, Nrf2 and MAPK signaling pathways.