title: Punicalagin inhibits neuroinflammation in LPS-activated rat primary microglia.
abstract: METHODS
  In this study, the effects of punicalagin on neuroinflammation in LPS-activated microglia were investigated.
  
  
  RESULTS
  The ability of punicalagin to reduce the production of TNF-α, IL-6 and prostaglandin E2 was measured in culture medium using enzyme immunoassay. TNF-α and IL-6 gene expression in mouse hippocampal slices was measured with PCR. cyclooxygenase-2 and microsomal prostaglandin E synthase 1 protein and mRNA were evaluated with Western blotting and PCR, respectively. Further experiments to investigate effects of punicalagin on protein expressions of inflammatory targets were also determined with Western blotting. Pretreatment of rat primary microglia with punicalagin (5-40 μM) prior to LPS (10 ng/mL) stimulation produced a significant (p < 0.05) inhibition of TNF-α, IL-6 and prostaglandin E2 production. Punicalagin completely abolished TNF-α and IL-6 gene expression in LPS-stimulated hippocampal slices. Protein and mRNA expressions of cyclooxygenase-2 and microsomal prostaglandin E synthase 1 were also reduced by punicalagin pretreatment. Results show that punicalagin interferes with NF-κB signalling through attenuation of NF-κB-driven luciferase expression, as well as inhibition of IκB phosphorylation and nuclear translocation of p65 subunit in the microglia.
  
  
  CONCLUSIONS
  These results suggest that punicalagin inhibits neuroinflammation in LPS-activated microglia through interference with NF-κB signalling, suggesting its potential as a nutritional preventive strategy in neurodegenerative disorders.
authors: Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield, UK.
authors: Olumayokun A
authors: OA
authors: Olajide
authors: Asit
authors: A
authors: Kumar
authors: Ravikanth
authors: R
authors: Velagapudi
authors: Uchechukwu P
authors: UP
authors: Okorji
authors: Bernd L
authors: BL
authors: Fiebich
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D009924:Organ Culture Techniques; D000071876:Prostaglandin-E Synthases; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D017207:Rats, Sprague-Dawley; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D047348:Hydrolyzable Tannins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D048029:TNF Receptor-Associated Factor 6; D014409:Tumor Necrosis Factor-alpha; C115642:punicalagin; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D000071876:Prostaglandin-E Synthases; C497818:Ptges protein, rat; D015232:Dinoprostone
keywords: Microglia; NF-κB; Neuroinflammation; Pomegranate; Punicalagin