title: Diammonium glycyrrhizinate attenuates Aβ(1-42) -induced neuroinflammation and regulates MAPK and NF-κB pathways in vitro and in vivo.
abstract: OBJECTIVE
  Beta-amyloid (Aβ)-mediated inflammation contributes to the progression and chronicity of Alzheimer's disease (AD), although the exact mechanism remains unclear. This study aimed to investigate whether diammonium glycyrrhizinate (DG) could inhibit Aβ-induced inflammation in vitro and in vivo and to explore the underlying mechanisms.
  
  
  METHODS
  Aβ(1-42)  was injected to bilateral hippocampus of mice to make the AD models in vivo. The levels of mRNA and protein of inflammatory cytokines were measured by real-time PCR and Western blotting, respectively. The viability of SH-SY5Y and HT-22 cells was determined by MTT. NF-κB p65 translocation was analyzed by Western blotting and immunostaining. Phosphorylation of ERK, p38, and JNK was tested by Western blotting.
  
  
  RESULTS
  DG suppressed Aβ(1-42) -induced activation of microglia and inflammation in vitro and in vivo. The media from Aβ(1-42) -activated microglia decreased the viability of SH-SY5Y and HT-22 cells, but it was rescued when pretreated with DG. DG could inhibit the activation of MAPK and NF-κB signaling pathways and attenuate the memory deficits in Aβ(1-42) -induced AD mice.
  
  
  CONCLUSIONS
  DG protects Aβ(1-42) -induced AD models in vitro and in vivo through reducing activation of microglia and inflammation, which may be involved in MAPK and NF-κB pathways.
authors.affiliation: Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.forename: Su-Lei
authors.initials: SL
authors.lastname: Wang
authors.forename: Lai
authors.initials: L
authors.lastname: Qian
authors.forename: Jia-Li
authors.initials: JL
authors.lastname: Jin
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Yun
authors.initials: Y
authors.lastname: Xu
authors.forename: Xiao-Lei
authors.initials: XL
authors.lastname: Zhu
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000818:Animals; D045744:Cell Line, Tumor; D019695:Glycyrrhizic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000502:physiology*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000633:toxicity*
chemical_list: D016229:Amyloid beta-Peptides; D018836:Inflammation Mediators; D016328:NF-kappa B; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D019695:Glycyrrhizic Acid