scholarly journals Quercetin-conjugated superparamagnetic iron oxide nanoparticles (QCSPIONs) increases Nrf2 expression via miR-27a mediation to prevent memory dysfunction in diabetic rats

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Shiva Ebrahimpour ◽  
Seyedeh Bahar Shahidi ◽  
Mahnoosh Abbasi ◽  
Zahra Tavakoli ◽  
Abolghasem Esmaeili
Keyword(s):  
Oxidative Stress ◽  
Iron Oxide ◽  
Iron Oxide Nanoparticles ◽  
Superparamagnetic Iron Oxide ◽  
Diabetic Rats ◽  
Expression Level ◽  
Oxide Nanoparticles ◽  
Antioxidant Genes ◽  
Expression Levels ◽  
Nrf2 Expression

Abstract Oxidative stress is one of the earliest defects involved in the development of diabetes-induced cognitive impairment. Nrf2 is the master regulator of the cellular antioxidant system can be regulated by some microRNAs. The study aimed to evaluate the effects of quercetin (QC) and quercetin-conjugated superparamagnetic iron oxide nanoparticles (QCSPIONs) on Nrf2-controlled antioxidant genes through the redox-sensitive miR-27a. Expression levels of miR-27a, Nrf2, SOD1, GPX1, and CAT were measured by quantitative real-time PCR. Moreover, the oxidative stress parameters including total antioxidant capacity (TAC) and histological alterations were investigated. The expression level of miR-27a was significantly up-regulated in diabetic rats. While expression levels of Nrf2, SOD1, GPX1, and CAT were significantly down-regulated under diabetic condition. Interestingly, QCSPIONs decreased expression level of miR-27a and subsequently enhanced the expression levels of Nrf2, SOD1, and CAT to the control level. No significant difference was observed in the expression level of GPX1. Besides, QC in pure and especially conjugated form was able to normalize TAC and regenerate pathological lesions in STZ-diabetic rats. Our result demonstrates that QCSPIONs as an effective combined therapy can decrease miR-27a expression, which in turn increases the Nrf2 expression and responsive antioxidant genes, resulting in improvement of memory dysfunction in diabetic rats.

scholarly journals Quercetin-conjugated superparamagnetic iron oxide nanoparticles enhances Nrf2 expression through miR-27a intervention to prevent memory dysfunction in diabetic rats

2020 ◽  
Author(s):  
Shiva Ebrahimpour ◽  
Seyedeh Bahar Shahidi ◽  
Mahnoosh Aabbasi ◽  
Zahra Tavakoli ◽  
Abolghasem Esmaeili
Keyword(s):  
Iron Oxide ◽  
Iron Oxide Nanoparticles ◽  
Superparamagnetic Iron Oxide ◽  
Diabetic Rats ◽  
Superparamagnetic Iron Oxide Nanoparticles ◽  
Expression Level ◽  
Oxide Nanoparticles ◽  
Antioxidant Genes ◽  
Expression Levels ◽  
Nrf2 Expression

Abstract Background: Oxidative stress is involved in the development of diabetes-induced cognitive impairment. Nrf2 as a redox-sensing gene can be regulated by some microRNAs. This study aimed to evaluate the effects of quercetin (QC) and quercetin-conjugated superparamagnetic iron oxide nanoparticles (QCSPIONs) on Nrf2-controlled antioxidant genes via the miR-27a. Streptozotocin was applied to produce type 1 diabetes in male Wistar rats. Animals (five groups of 8 rats) were treated for 35 days. Real-time polymerase chain reaction method was applied to assess the expression levels of miR-27a, Nrf2, SOD1, GPX1, and CAT. Moreover, total antioxidant capacity (TAC) and histological alterations were investigated. Results: A significant up-regulation in the expression level of miR-27a was observed in diabetic rats in comparison to control (p<0.01). The mRNA expression levels of Nrf2, SOD1, GPX1 and CAT were significantly down-regulated under diabetic condition (p<0.0001, p<0.01, p<0.0001 and p<0.0001, respectively). Interestingly, QCSPIONs decreased expression level of miR-27a (p<0.01) and subsequently enhanced the expression levels of the Nrf2 (P<0.5), SOD1 (P<0.0204) and CAT (P<0.01) to the control level. Significant difference was not recognized in the expression level of GPX1 under QCSPIONs treatment. In addition, QC in pure and especially conjugated form was able to normalize TAC (p<0.01) and regenerate pathological lesions in STZ-diabetic rats. Conclusions: Result demonstrates that QCSPIONs as an effective combined therapy can reduce the miR-27a expression, that in turn increases the mRNA Nrf2 expression and its responsive antioxidant genes, resulting in the prevention of diabetic complications.

scholarly journals Effects of quercetin-conjugated with superparamagnetic iron oxide nanoparticles on learning and memory improvement through targeting microRNAs/NF-κB pathway

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Shiva Ebrahimpour ◽  
Abolghasem Esmaeili ◽  
Fariba Dehghanian ◽  
Siamak Beheshti
Keyword(s):  
Iron Oxide ◽  
Iron Oxide Nanoparticles ◽  
Superparamagnetic Iron Oxide ◽  
Diabetic Rats ◽  
Superparamagnetic Iron Oxide Nanoparticles ◽  
Oxide Nanoparticles ◽  
Expression Levels ◽  
Memory Improvement ◽  
Tnf Α ◽  
Ameliorative Effect

Abstract Quercetin-conjugated superparamagnetic iron oxide nanoparticles (QCSPIONs) have an ameliorative effect on diabetes-induced memory impairment. The current study aimed to compare the effect of quercetin (QC) and QCSPIONs on inflammation-related microRNAs and NF-κB signaling pathways in the hippocampus of diabetic rats. The expression levels of miR-146a, miR-9, NF-κB, and NF-κB-related downstream genes, including TNF-α, BACE1, AβPP, Bax, and Bcl-2 were measured using quantitative real-time PCR. To determine the NF-κB activity, immunohistochemical expression of NF-κB/p65 phosphorylation was employed. Computer simulated docking analysis also performed to find the QC target proteins involved in the NF-κB pathway. Results indicate that diabetes significantly upregulated the expression levels of miR-146a, miR-9, TNF-α, NF-κB, and subsequently AβPP, BACE1, and Bax. Expression analysis shows that QCSPIONs are more effective than pure QC in reducing the expression of miR-9. Interestingly, QCSPIONs reduce the pathological activity of NF-κB and subsequently normalize BACE1, AβPP, and the ratio of Bax/Bcl-2 expression better than pure QC. Comparative docking analyses also show the stronger binding affinity of QC to IKK and BACE1 proteins compared to specific inhibitors of each protein. In conclusion, our study suggests the potent efficacy of QCSPIONs as a promising drug delivery system in memory improvement through targeting the NF-κB pathway.

scholarly journals Iron oxide nanoparticles promote vascular endothelial cells survival from oxidative stress by enhancement of autophagy

2019 ◽  
Vol 6 (4) ◽  
pp. 221-229 ◽  
Author(s):  
Jimei Duan ◽  
Jiuju Du ◽  
Rongrong Jin ◽  
Wencheng Zhu ◽  
Li Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Iron Oxide ◽  
Adjuvant Therapy ◽  
Iron Oxide Nanoparticles ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Superparamagnetic Iron Oxide ◽  
Disease Diagnosis ◽  
Oxide Nanoparticles

Abstract Dextran-coated superparamagnetic iron oxide nanoparticles (Dex-SPIONs) are excellent magnetic resonance imaging contrast agents for disease diagnosis and therapy. They can be delivered to target tissues mainly though vascular endothelium cells, which are major targets of oxidative stress. In cardiovascular cells, autophagy serves primarily on a pro-survival approach that protects the cells from oxidative stress even some autophagy inducers have been developed for adjuvant therapy of cardiovascular disorders. Our study demonstrated that the nanoparticles could be taken up by human umbilical vein endothelial cells (HUVECs) without causing obvious cytotoxicity but triggering autophagy. Furthermore, our results revealed that Dex-SPIONs could enhance HUVECs survival and reverse the reduction of nitric oxide secretion under the condition of H2O2 damage. However, these effects could be diminished by the autophagy inhibitor. In particular, we discovered that Dex-SPIONs evoked autophagy in HUVECs by reducing the phosphorylation of PRAS40, an upstream regulator of autophagy initiation. These results suggested that Dex-SPIONs functions as an autophagic-related antioxidant in HUVECs which may be utilized as an adjuvant therapy to cardiovascular disease associated with oxidative stress.

scholarly journals Quercetin-Conjugated Superparamagnetic Iron Oxide Nanoparticles Protect AlCl3-Induced Neurotoxicity in a Rat Model of Alzheimer’s Disease via Antioxidant Genes, APP Gene, and miRNA-101

2021 ◽  
Vol 14 ◽  
Author(s):  
Elnaz Amanzadeh Jajin ◽  
Abolghasem Esmaeili ◽  
Soheila Rahgozar ◽  
Maryam Noorbakhshnia
Keyword(s):  
Antioxidant Enzymes ◽  
Cognitive Impairment ◽  
Iron Oxide ◽  
Iron Oxide Nanoparticles ◽  
Superparamagnetic Iron Oxide ◽  
Control Group ◽  
Oxide Nanoparticles ◽  
Behavioral Tests ◽  
Expression Levels ◽  
App Gene

Alzheimer’s disease (AD) is a neurodegenerative disease with cognitive impairment. Oxidative stress in neurons is considered as a reason for development of AD. Antioxidant agents such as quercetin slow down AD progression, but the usage of this flavonoid has limitations because of its low bioavailability. We hypothesized that quercetin-conjugated superparamagnetic iron oxide nanoparticles (QT-SPIONs) have a better neuroprotective effect on AD than free quercetin and regulates the antioxidant, apoptotic, and APP gene, and miRNA-101. In this study, male Wistar rats were subjected to AlCl3, AlCl3 + QT, AlCl3 + SPION, and AlCl3 + QT-SPION for 42 consecutive days. Behavioral tests and qPCR were used to evaluate the efficiency of treatments. Results of behavioral tests revealed that the intensity of cognitive impairment was decelerated at both the middle and end of the treatment period. The effect of QT-SPIONs on learning and memory deficits were closely similar to the control group. The increase in expression levels of APP gene and the decrease in mir101 led to the development of AD symptoms in rats treated with AlCl3 while these results were reversed in the AlCl3 + QT-SPIONs group. This group showed similar results with the control group. QT-SPION also decreased the expression levels of antioxidant enzymes along with increases in expression levels of anti-apoptotic genes. Accordingly, the antioxidant effect of QT-SPION inhibited progression of cognitive impairment via sustaining the balance of antioxidant enzymes in the hippocampus of AD model rats.

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