ABSTRACT
This study has investigated the effect of a potent bioflavonoid, troxerutin,on diabetes-induced changes in pro-inflammatory mediators and expression ofmicroRNA-146a and nuclear factor-kappa-B (NF-κB) signaling pathway in aortic tissueof type-I diabetic rats. Male Wistar rats were randomly divided into four groups(n = 6/each): healthy, healthy-troxerutin, diabetic, and diabetic-troxerutin. Diabeteswas induced by streptozotocin injection (60 mg/kg; intraperitoneally) and lasted 10weeks. Troxerutin (150 mg/kg/day) was administered orally for last month of experiment.Inflammatory cytokines IL-1, IL-6, and TNF-, as well as intercellular adhesionmolecule-1 (ICAM-1), vascular cell adhesion molecule (VCAM), cyclooxygenase-II(COX-II), and inducible-nitric oxide synthase (iNOS) were measured on aortic samplesby enzyme-linked immunosorbent assay. Gene expressions for transcription factorNF-κB, interleukin-1 receptor-associated kinase-1 (IRAK-1), TNF receptor-associatedfactor-6 (TRAF-6), and microRNA-146a were determined using real-time polymerasechain reaction. Ten-week diabetes significantly increased mRNA levels of IRAK-1,TRAF-6, NF-κB, and protein levels of cytokines IL-1, IL-6, TNF-, adhesion moleculesICAM-1, VCAM, and iNOS, COX-II, and decreased expression of microRNA-146a ascompared with healthy rats (p < 0.05 to p < 0.01). However, one month treatmentof diabetic rats with troxerutin restored glucose and insulin levels, significantly decreasedexpression of inflammatory genes and pro-inflammatory mediators andincreased microRNA level in comparison to diabetic group (p < 0.05 to p < 0.01). Inhealthy rats, troxerutin had significant reducing effect only on NF-κB, TNF- and COXIIlevels (p < 0.05). Beside slight improvement of hyperglycemia, troxerutin preventedthe activation of NF-κB-dependent inflammatory signaling in
ABSTRACT
This study has investigated the effect of a potent bioflavonoid, troxerutin,on diabetes-induced changes in pro-inflammatory mediators and expression ofmicroRNA-146a and nuclear factor-kappa-B (NF-κB) signaling pathway in aortic tissueof type-I diabetic rats. Male Wistar rats were randomly divided into four groups(n = 6/each): healthy, healthy-troxerutin, diabetic, and diabetic-troxerutin. Diabeteswas induced by streptozotocin injection (60 mg/kg; intraperitoneally) and lasted 10weeks. Troxerutin (150 mg/kg/day) was administered orally for last month of experiment.Inflammatory cytokines IL-1, IL-6, and TNF-, as well as intercellular adhesionmolecule-1 (ICAM-1), vascular cell adhesion molecule (VCAM), cyclooxygenase-II(COX-II), and inducible-nitric oxide synthase (iNOS) were measured on aortic samplesby enzyme-linked immunosorbent assay. Gene expressions for transcription factorNF-κB, interleukin-1 receptor-associated kinase-1 (IRAK-1), TNF receptor-associatedfactor-6 (TRAF-6), and microRNA-146a were determined using real-time polymerasechain reaction. Ten-week diabetes significantly increased mRNA levels of IRAK-1,TRAF-6, NF-κB, and protein levels of cytokines IL-1, IL-6, TNF-, adhesion moleculesICAM-1, VCAM, and iNOS, COX-II, and decreased expression of microRNA-146a ascompared with healthy rats (p < 0.05 to p < 0.01). However, one month treatmentof diabetic rats with troxerutin restored glucose and insulin levels, significantly decreasedexpression of inflammatory genes and pro-inflammatory mediators andincreased microRNA level in comparison to diabetic group (p < 0.05 to p < 0.01). Inhealthy rats, troxerutin had significant reducing effect only on NF-κB, TNF- and COXIIlevels (p < 0.05). Beside slight improvement of hyperglycemia, troxerutin preventedthe activation of NF-κB-dependent inflammatory signaling in