Alpha-Linolenic Acid Exerts an Endothelial Protective Effect against High Glucose Injury via PI3K/Akt Pathway

Abstract

Mounting evidence has indicated that the cardiovascular protective effects of dietary alpha-linolenic acid (ALA), but whether ALA exerts an endothelial protective effect against high glucose injury and the underlying mechanisms remain largely unknown. Streptozocin-induced diabetic rats were randomized treated orally for 4 weeks with vehicle (0.01% alcohol) or ALA (500 µg/kg per day by gavage). Human umbilical vein endothelial cells (HUVECs) were exposed to high glucose (28 mmol/L) stimulation for 48 hours. ALA significantly improved concentration-dependent vasorelaxation to ACh in diabetic aortic segments and inhibited endothelial inflammation as evidenced by decreased soluble P-selectin and intercellular adhesion molecule-1 (ICAM-1) in diabetic rats. Furthermore, both P-selectin and ICAM-1 expression were increased significantly in high glucose-induced HUVECs, resulting in enhanced neutrophils adhesion to HUVECs compared with normal glucose group. Treatment with ALA (50 µmol/L) increased Akt phosphorylation, attenuated P-selectin and ICAM-1 expressions and thus inhibited neutrophils adhesion in HUVECs exposed to high glucose, all of which was blocked by the PI3K inhibitors LY294002 and wortmannin. These data indicates that ALA inhibits endothelial inflammation and improved endothelial function in STZ-induced diabetic rats. The anti-adhesive effect of ALA against high glucose injury may partially be mediated by the PI3K/Akt pathway.

κ-Opioid Receptor Stimulation Improves Endothelial Function via Akt-stimulated NO Production in Hyperlipidemic Rats

“…Previous studies demonstrated that therapy has ability of activating the PI3K/Akt pathway, restoring eNOS activity and suppressing oxidation/nitration may be ideal solution to endothelial dysfunction5111213. In the present study we proved for the first time that preventive treatment with U50,488H showed a significant effect to ameliorate endothelial dysfunction in hyperlipidemia through activation of κ-OR and the PI3K/Akt/eNOS pathway.…”

“…As an independent risk factor of atherosclerosis, hyperlipidemia, especially hypercholesterolemia (as shown in our rat model), induces a series of molecular events including ox-LDL accumulation, eNOS uncoupling and iNOS upregulation, thus impairing endothelium 2 4 9 10 . Previous studies demonstrated that therapy has ability of activating the PI3K/Akt pathway, restoring eNOS activity and suppressing oxidation/nitration may be ideal solution to endothelial dysfunction 5 11 12 13 . In the present study we proved for the first time that preventive treatment with U50,488H showed a significant effect to ameliorate endothelial dysfunction in hyperlipidemia through activation of κ-OR and the PI3K/Akt/eNOS pathway.…”

Reversibility of endothelial dysfunction in diabetes: role of polyphenols

“…Daidzein, a phyto-oestrogen, reversed changes in vascular reactivity through NO • and PG-related pathways, and attenuated oxidative stress in aortic tissue of diabetic rats (146) . Other polyphenolic compounds such as epigallocatechin gallate (EGCG), hesperetin, α-linolenic acid, ferulic acid and catechin hydrate have also been reported to reverse endothelial dysfunction through the activation of the PI3K/ Akt/eNOS pathway, as demonstrated in both in vitro and in vivo diabetic models (147)(148)(149)(150)(151) .…”

Effects of Modified Sanzi Yangqin Decoction on Tyrosine Phosphorylation of IRS‐1 in Skeletal Muscle of Type 2 Diabetic Rats

“…Sanzi Yangqin Decoction consists of perilla fruit, radish seed, and white mustard seed. Perilla fruit is rich in alpha-linolenic acid which exerts an endothelial protective effect against high glucose injury via PI3K/Akt pathway [ 13 ]. Previous pharmacological experiments showed that oleanolic acid, an important ingredient in glossy privet fruit, has hypoglycemic effects [ 14 , 15 ].…”