title: Oleanolic acid ameliorates high glucose-induced endothelial dysfunction via PPARδ activation.
abstract: Oleanolic acid (3β-hydroxyolean-12-en-28-oic acid, OA) is a pentacyclic triterpenes widely distributed in food, medicinal plants and nutritional supplements. OA exhibits various pharmacological properties, such as hepatoprotective and anti-tumor effects. In this study, we analyzed the effect of OA on endothelial dysfunction induced by high glucose in human vascular endothelial cells (ECs). Western blotting showed that OA attenuated high glucose-reduced nitric production oxide (NO) as well as Akt-Ser473and eNOS-Ser1177phosphorylation in cultured human umbilical vein ECs (HUVECs). Next, luciferase reporter assay showed that OA activated peroxisome proliferators-activated receptor δ (PPARδ) activity. Quantitative reverse transcriptase PCR (qRT-PCR) demonstrated that OA increased the expressions of PPARδ target genes (PDK4, ADRP and ANGPTL4) in ECs. Meanwhile, the induced expressions of PDK4, ADRP and ANGPTL4 by OA were inhibited by GSK0660, a specific antagonist of PPARδ. In addition, inhibition of PPARδ abolished OA-induced the Akt-Ser473and eNOS-Ser1177phosphorylation, and NO production. Finally, by using Multi Myograph System, we showed that OA prevented high glucose-impaired vasodilation. This protective effect on vasodilation was inhibited in aortic rings pretreated with GSK0660. Collectively, we demonstrated that OA improved high glucose-impaired endothelial function via a PPARδ-mediated mechanism and through eNOS/Akt/NO pathway.
authors.affiliation: Cardiovascular Research Center, Xi'an Jiaotong University, Xi'an, 710061, China.
authors.forename: Zihui
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Cardiovascular Research Center, Xi'an Jiaotong University, Xi'an, 710061, China.
authors.forename: Manli
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Cardiovascular Research Center, Xi'an Jiaotong University, Xi'an, 710061, China.
authors.forename: Xinya
authors.initials: X
authors.lastname: Xie
authors.affiliation: Cardiovascular Research Center, Xi'an Jiaotong University, Xi'an, 710061, China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Yang
authors.affiliation: Cardiovascular Research Center, Xi'an Jiaotong University, Xi'an, 710061, China.
authors.forename: Xinfeng
authors.initials: X
authors.lastname: Wang
authors.affiliation: Cardiovascular Research Center, Xi'an Jiaotong University, Xi'an, 710061, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Cardiovascular Research Center, Xi'an Jiaotong University, Xi'an, 710061, China.|The Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, 116044, China.
authors.forename: Nanping
authors.initials: N
authors.lastname: Wang
mesh_terms: D002478:Cells, Cultured; D005947:Glucose / Q000633:toxicity*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009828:Oleanolic Acid / Q000494:pharmacology*; D047494:PPAR delta / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D014664:Vasodilation
chemical_list: D047494:PPAR delta; D009569:Nitric Oxide; D009828:Oleanolic Acid; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose