title: Tectorigenin Attenuates Palmitate-Induced Endothelial Insulin Resistance via Targeting ROS-Associated Inflammation and IRS-1 Pathway.
abstract: Tectorigenin is a plant isoflavonoid originally isolated from the dried flower of Pueraria thomsonii Benth. Although its anti-inflammatory and anti-hyperglycosemia effects have been well documented, the effect of tectorigenin on endothelial dysfunction insulin resistance involved has not yet been reported. Herein, this study aims to investigate the action of tectorigenin on amelioration of insulin resistance in the endothelium. Palmitic acid (PA) was chosen as a stimulant to induce ROS production in endothelial cells and successfully established insulin resistance evidenced by the specific impairment of insulin PI3K signaling. Tectorigenin effectively inhibited the ability of PA to induce the production of reactive oxygen species and collapse of mitochondrial membrane potential. Moreover, tectorigenin presented strong inhibition effect on ROS-associated inflammation, as TNF-α and IL-6 production in endothelial cells was greatly reduced with suppression of IKKβ/NF-κB phosphorylation and JNK activation. Tectorigenin also can inhibit inflammation-stimulated IRS-1 serine phosphorylation and restore the impaired insulin PI3K signaling, leading to a decreased NO production. These results demonstrated its positive regulation of insulin action in the endothelium. Meanwhile, tectorigenin down-regulated endothelin-1 and vascular cell adhesion molecule-1 overexpression, and restored the loss of insulin-mediated vasodilation in rat aorta. These findings suggested that tectorigenin could inhibit ROS-associated inflammation and ameliorated endothelial dysfunction implicated in insulin resistance through regulating IRS-1 function. Tectorigenin might have potential to be applied for the management of cardiovascular diseases involved in diabetes and insulin resistance.
authors.affiliation: Department of Resource Science of Traditional Chinese Medicines, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Xiao-Lan
authors.initials: XL
authors.lastname: Cheng
authors.forename: Dong-Yan
authors.initials: DY
authors.lastname: Zhang
authors.forename: Xue-Jiao
authors.initials: XJ
authors.lastname: Gao
authors.forename: Ling
authors.initials: L
authors.lastname: Zhou
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Qin
authors.forename: Guo-Yong
authors.initials: GY
authors.lastname: Xie
authors.forename: Kang
authors.initials: K
authors.lastname: Liu
authors.forename: Yong
authors.initials: Y
authors.lastname: Qin
authors.forename: Bao-Lin
authors.initials: BL
authors.lastname: Liu
authors.forename: Min-Jian
authors.initials: MJ
authors.lastname: Qin
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism*; D007333:Insulin Resistance / Q000276:immunology*; D007529:Isoflavones / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D019308:Palmitic Acid / Q000009:adverse effects*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D007529:Isoflavones; D017382:Reactive Oxygen Species; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D019308:Palmitic Acid; C120039:tectorigenin