title: Luteolin inhibits inflammatory response and improves insulin sensitivity in the endothelium.
abstract: Endothelial insulin resistance is tightly associated with diabetic cardiovascular complication, and it is well known that inflammation plays an important role in the development of insulin resistance. Luteolin, a flavonoid abundant in some medical and eatable plants, is a potent inhibitor of inflammation. It is also reported that luteolin exhibited some chemoprotection capability to the endothelial integrity. This study aims to clarify whether the anti-inflammatory potency of luteolin contributes to amelioration of insulin resistance in the endothelium. Palmitate (PA) stimulation markedly reduced insulin-mediated endothelium-dependent relaxation in rat aorta, while luteolin pretreatment effectively reversed the effects of palmitate in a concentration-dependent manner. PA stimulation also evoked inflammatory response in endothelial cells. When the cells were pretreated with luteolin, IKKβ phosphorylation were reduced, which, in turn, blocked the NF-κB activation through attenuating P65 phosphorylation. At the same time, it was also found that the gene over-expressions for TNF-α and IL-6 were also reduced by luteolin pretreatment. When endothelial cells were stimulated with PA, the insulin signaling cascades were impaired with reduced insulin-dependent production of NO. Again, pretreatment of luteolin could effectively reverse the effects of PA. Luteolin modulated the Ser/Thr phosphorylation of insulin receptor substrates-1 and restored downstream Akt/eNOS activation, resulting in increased NO production in the presence of insulin. In conclusion, these results suggested that luteolin ameliorated inflammation related endothelial insulin resistance in an IKKβ/IRS-1/Akt/eNOS-dependent pathway.
authors.affiliation: First People's Hospital of Shanghai Jiaotong University, 100 Haining Road, Shanghai, PR China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Deqiu
authors.forename: Liu
authors.initials: L
authors.lastname: Kang
authors.forename: Yi
authors.initials: Y
authors.lastname: Jiali
authors.forename: Liu
authors.initials: L
authors.lastname: Baolin
authors.forename: Liu
authors.initials: L
authors.lastname: Gaolin
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D016207:Cytokines / Q000235:genetics; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D051550:I-kappa B Kinase / Q000378:metabolism; D066298:In Vitro Techniques; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007328:Insulin / Q000494:pharmacology*; D055504:Insulin Receptor Substrate Proteins / Q000737:chemistry / Q000378:metabolism; D047311:Luteolin / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010168:Palmitates / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D016207:Cytokines; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D016328:NF-kappa B; D010168:Palmitates; D012333:RNA, Messenger; D009569:Nitric Oxide; D012694:Serine; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt; D051550:I-kappa B Kinase; D047311:Luteolin