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

作者：Khan Salman^*; Choi Ran Joo; Lee Joohee; Kim Yeong Shik^*

来源：European Journal of Pharmacology, 2016, 774: 95-104.

DOI：10.1016/j.ejphar.2016.02.008

• Neuropathic pain
• Anti-neuroinflammation
• STZ-induced diabetic type I
• Anomalin
• N2a cells

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 IKK alpha/beta, I kappa B alpha, 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-kappa B, Nrf2 and MAPK signaling pathways.

• 出版日期2016-3-5
• 单位McGill