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Quercetin and quercetin-3-O -glucuronide are equally effective in ameliorating endothelial insulin resistance through inhibition of reactive oxygen species-associated inflammation
- Source :
- Molecular Nutrition & Food Research. 57:1037-1045
- Publication Year :
- 2013
- Publisher :
- Wiley, 2013.
-
Abstract
- Scope Quercetin represents antioxidative/antiinflammatory flavonoids widely distributed in the human diet. Quercetin is efficiently metabolized during absorption to quercetin-3-O-glucuronide. This study aims to parallelly investigate whether quercetin and quercetin-3-O-glucuronide exert protection against palmitate (PA)-induced inflammation and insulin resistance in the endothelium. Methods and results Human umbilical vein endothelial cells were pretreated with quercetin and quercetin-3-O-glucuronide for 30 min, and then incubated with 100 μM PA for 30 min or 12 h with or without insulin. PA stimulation led to reactive oxygen species (ROS) production with collapse of mitochondrial membrane potential (Δψm). Quercetin and quercetin-3-O-glucuronide inhibited ROS overproduction and effectively restored Δψm, demonstrating their chemorpotection of mitochondrial function through antioxidative actions. Also, quercetin and quercetin-3-O-glucuronide inhibited ROS-associated inflammation by inhibition of interleukin-6 and tumor necrosis factor-α production with suppression of IKKβ/NF-κB phosphorylation. Inflammation impaired insulin PI3K signaling and reduced insulin-mediated nitric oxide (NO) production. Quercetin and quercetin-3-O-glucuronide facilitated PI3K signaling by positive regulation of serine/tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and restoration of downstream Akt/eNOS activation, leading to an increased insulin-mediated NO level. Conclusion The above-mentioned evidence indicates that quercetin and quercetin-3-O-glucuronide are equally effective in inhibiting ROS-associated inflammation and ameliorating insulin resistant endothelial dysfunction by beneficial regulation of IRS-1 function.
- Subjects :
- medicine.medical_specialty
Nitric Oxide Synthase Type III
medicine.medical_treatment
Palmitates
Inflammation
medicine.disease_cause
chemistry.chemical_compound
Insulin resistance
Internal medicine
Human Umbilical Vein Endothelial Cells
medicine
Humans
heterocyclic compounds
Phosphorylation
Protein kinase B
chemistry.chemical_classification
Reactive oxygen species
biology
Interleukin-6
Tumor Necrosis Factor-alpha
Insulin
Anti-Inflammatory Agents, Non-Steroidal
NF-kappa B
medicine.disease
I-kappa B Kinase
Oxidative Stress
Insulin receptor
Endocrinology
chemistry
Insulin Receptor Substrate Proteins
biology.protein
Quercetin
Endothelium, Vascular
Insulin Resistance
medicine.symptom
Reactive Oxygen Species
Proto-Oncogene Proteins c-akt
Oxidative stress
Food Science
Biotechnology
Subjects
Details
- ISSN :
- 16134125
- Volume :
- 57
- Database :
- OpenAIRE
- Journal :
- Molecular Nutrition & Food Research
- Accession number :
- edsair.doi.dedup.....c0a657be272d59f433015e1d7756937a