title: Modulation of hippocampal gene expression of microRNA-146a/microRNA-155-nuclear factor-kappa B inflammatory signaling by troxerutin in healthy and diabetic rats.
abstract: OBJECTIVE
  Inflammation plays a critical role in the progression of diabetic complications such as neurological disorders. Previous reports have indicated the memory-improving effect of troxerutin, in rat hippocampus, but the underlying mechanisms are unclear. Hence, we have investigated the effect of troxerutin pretreatment on gene expressions of inflammation-related microRNAs (miRs), miR-146a and miR-155, and nuclear factor-kappa B (NF-κB) signaling pathway in the hippocampus of healthy and diabetic rats.
  
  
  METHODS
  Wistar rats were randomly divided into four groups (control, control + troxerutin, diabetic, and diabetic + troxerutin). Diabetes was induced by a single i.p. injection of streptozotocin (50 mg/kg). Troxerutin (150 mg/kg) was orally administered in animals for 1 month. After 10 weeks of diabetes, animals were anesthetized and decapitated for the isolation of hippocampus. The expression of miR-146a and miR-155 and the messenger RNA (mRNA) expressions of NF-κB, interleukin-1 receptor-associated kinase-1 (IRAK-1), and tumor necrosis factor receptor-associated factor-6 (TRAF-6) were analyzed by real-time polymerase chain reaction.
  
  
  RESULTS
  Diabetes significantly increased hippocampal mRNA levels of NF-κB, IRAK-1, and TRAF-6 compared with nondiabetic rats (P< 0.05); however, pretreatment with troxerutin decreased them in both diabetic and nondiabetic animals, independent of its glycemic effect (P< 0.05). The expression levels of miR-146a and miR-155 were decreased in diabetic group as compared to the control (P< 0.01).
  
  
  CONCLUSIONS
  These findings showed that troxerutin could inhibit the inflammatory NF-κB pathway in the hippocampus of diabetic rats, which may be due to the negative feedback loop regulated by miR-146a.
authors.affiliation: Neuroscience Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Raana
authors.initials: R
authors.lastname: Yavari
authors.affiliation: Neuroscience Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Badalzadeh
authors.affiliation: Tuberculosis and Lung Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Alipour
authors.affiliation: Department of Physiology, Islamic Azad University, Tabriz Branch, Tabriz, Iran.
authors.forename: Seyed Mahmoud
authors.initials: SM
authors.lastname: Tabatabaei
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006896:Hydroxyethylrutoside / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D001786:Blood Glucose; D006896:Hydroxyethylrutoside; C554180:MIRN146 microRNA, rat; C580597:MIRN155 microRNA, rat; D035683:MicroRNAs; D016328:NF-kappa B; C005865:troxerutin
keywords: Diabetes; inflammation; microRNA-146a; nuclear factor-kappa B; troxerutin