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BMC pharmacology & toxicology
12 21, 2023;24 (1): 81.

In diabetic male Wistar rats, quercetin-conjugated superparamagnetic iron oxide nanoparticles have an effect on the SIRT1/p66Shc-mediated pathway related to cognitive impairment.

Mahnaz Karami Chamgordani, Akram Bardestani, Shiva Ebrahimpour, Abolghasem Esmaeili
Author Information
  1. Mahnaz Karami Chamgordani: Department of Cell and Molecular Biology & Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, P.O. Box: 8174673441, Iran.
  2. Akram Bardestani: Department of Cell and Molecular Biology & Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, P.O. Box: 8174673441, Iran.
  3. Shiva Ebrahimpour: Department of Cell and Molecular Biology & Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, P.O. Box: 8174673441, Iran.
  4. Abolghasem Esmaeili: Department of Cell and Molecular Biology & Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, P.O. Box: 8174673441, Iran. aesmaeili@sci.ui.ac.ir.
PMID: 38129872 DOI: 10.1186/s40360-023-00725-3

Abstract

BACKGROUND: Quercetin (QC) possesses a variety of health-promoting effects in pure and in conjugation with nanoparticles. Since the mRNA-SIRT1/p66Shc pathway and microRNAs (miRNAs) are implicated in the oxidative process, we aimed to compare the effects of QC and QC-conjugated superparamagnetic iron oxide nanoparticles (QCSPIONs) on this pathway.
METHODS: Through the use of the chemical coprecipitation technique (CPT), SPIONs were synthesized, coated with dextran, and conjugated with quercetin. Adult male Wistar rats were given intraperitoneal injections of streptozotocin to look for signs of type 1 diabetes (T1D). The animals were randomized into five groups: the control group got deionized water (DI), free QC solution (25 mg/kg), SPIONs (25 mg/kg), and QCSPIONs (25 mg/kg), and all groups received repeat doses administered orally over 35 days. Real-time quantitative PCR was used to assess the levels of miR-34a, let-7a-p5, SIRT1, p66Shc, CASP3, and PARP1 expression in the hippocampus of diabetic rats.
RESULTS: In silico investigations identified p66Shc, CASP3, and PARP1 as targets of let-7a-5p and miR-34a as possible regulators of SIRT1 genes. The outcomes demonstrated that diabetes elevated miR-34a, p66Shc, CASP3, and PARP1 and downregulated let-7a-5p and SIRT1 expression. In contrast to the diabetic group, QCSPIONs boosted let-7a-5p expression levels and consequently lowered p66Shc, CASP3, and PARP1 expression levels. QCSPIONs also reduced miR-34a expression, which led to an upsurge in SIRT1 expression.
CONCLUSION: Our results suggest that QCSPIONs can regulate the SIRT1/p66Shc-mediated signaling pathway and can be considered a promising candidate for ameliorating the complications of diabetes.

Keywords

Diabetes Hippocampus Quercetin SIRT1/p66Shc-mediated pathway Superparamagnetic iron oxide nanoparticles

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MeSH Term

Rats
Male
Animals
Rats, Wistar
Quercetin
Src Homology 2 Domain-Containing, Transforming Protein 1
Caspase 3
Diabetes Mellitus, Experimental
Sirtuin 1
MicroRNAs
Magnetic Iron Oxide Nanoparticles
Cognitive Dysfunction

Chemicals

Quercetin
SHC1 protein, human
Src Homology 2 Domain-Containing, Transforming Protein 1
Caspase 3
Sirtuin 1
MicroRNAs
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 1

Word Cloud

Created with Highcharts 10.0.0expressionpathwayQCSPIONsnanoparticlesmiR-34aSIRT1p66ShcCASP3PARP1QCironoxideratsdiabetes25 mg/kglevelsdiabeticlet-7a-5pSIRT1/p66Shc-mediatedQuercetineffectssuperparamagneticSPIONsmaleWistargroupcanBACKGROUND:possessesvarietyhealth-promotingpureconjugationSincemRNA-SIRT1/p66ShcmicroRNAsmiRNAsimplicatedoxidativeprocessaimedcompareQC-conjugatedMETHODS:usechemicalcoprecipitationtechniqueCPTsynthesizedcoateddextranconjugatedquercetinAdultgivenintraperitonealinjectionsstreptozotocinlooksignstype1T1Danimalsrandomizedfivegroups:controlgotdeionizedwaterDIfreesolutiongroupsreceivedrepeatdosesadministeredorally35daysReal-timequantitativePCRusedassesslet-7a-p5hippocampusRESULTS:silicoinvestigationsidentifiedtargetspossibleregulatorsgenesoutcomesdemonstratedelevateddownregulatedcontrastboostedconsequentlyloweredalsoreducedledupsurgeCONCLUSION:resultssuggestregulatesignalingconsideredpromisingcandidateamelioratingcomplicationsquercetin-conjugatedeffectrelatedcognitiveimpairmentDiabetesHippocampusSuperparamagnetic

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