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 RESEARCH ARTICLE
Year : 2016  |  Volume : 48  |  Issue : 6  |  Page : 675-680

Modulation of hippocampal gene expression of microRNA-146a/microRNA-155-nuclear factor-kappa B inflammatory signaling by troxerutin in healthy and diabetic rats


1 Neuroscience Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
2 Neuroscience Research Center; Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
3 Tuberculosis and Lung Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
4 Department of Physiology, Islamic Azad University, Tabriz Branch, Tabriz, Iran

Correspondence Address:
Reza Badalzadeh
Neuroscience Research Center; Immunology Research Center, Tabriz University of Medical Sciences, Tabriz
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0253-7613.194847

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Objectives: 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. Materials and 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). Conclusion: 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.






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