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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
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.