title: Attenuation of neuropathic pain and neuroinflammatory responses by a pyranocoumarin derivative, anomalin in animal and cellular models.
abstract: 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.
authors: Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan; The Alan Edwards Centre for Research on Pain, McGill University, Montreal, Quebec, Canada; College of Pharmacy, Seoul National University, Seoul, Republic of Korea. Electronic address: skhan@qau.edu.pk.
authors: Salman
authors: S
authors: Khan
authors: College of Pharmacy, Seoul National University, Seoul, Republic of Korea; Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom.
authors: Ran Joo
authors: RJ
authors: Choi
authors: College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
authors: Joohee
authors: J
authors: Lee
authors: College of Pharmacy, Seoul National University, Seoul, Republic of Korea. Electronic address: kims@snu.ac.kr.
authors: Yeong Shik
authors: YS
authors: Kim
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003080:Cold Temperature / Q000009:adverse effects; D003374:Coumarins / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D051546:Cyclooxygenase 2 / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000187:drug effects / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism; D009437:Neuralgia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D039681:Pyranocoumarins / Q000737:chemistry*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats
chemical_list: D000975:Antioxidants; D003374:Coumarins; D016207:Cytokines; D016328:NF-kappa B; D039681:Pyranocoumarins; D012333:RNA, Messenger; D009569:Nitric Oxide; C065837:anomalin; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2
keywords: Anomalin; Anti-neuroinflammation; N2a cells; Neuropathic pain; STZ-induced diabetic type I