In:
The American Journal of Chinese Medicine, World Scientific Pub Co Pte Ltd, Vol. 47, No. 03 ( 2019-01), p. 541-557
Abstract:
Oxidative stress has been implicated in the pathogenesis of atherosclerotic cardiovascular diseases. Dietary supplementation of anti-oxidants has been reported to have beneficial effects on the prevention of atherogenic diseases. Luteolin (a natural flavonoid) has been shown to possess antimutagenic, antitumorigenic, anti-oxidant and anti-inflammatory properties. However, the effects and underlying molecular mechanisms of luteolin on cardiovascular systems are poorly explored. Therefore, the aim of the present study was to test whether luteolin could protect against oxidative stress-induced endothelial cell injury and explore the underlying mechanisms. In this study, human umbilical vein endothelial cells (HUVECs) were pre-treated with luteolin followed by hydrogen peroxide induction (H 2 O 2 ). Our results showed that luteolin protected against H 2 O 2 -induced oxidative stress and ameliorated ROS and superoxide generation. In addition, we found that luteolin treatment inhibited the H 2 O 2 -induced membrane assembly of NADPH oxidase subunits, which was further confirmed by specifically inhibiting NADPH oxidase using DPI treatment. Furthermore, pAMPK protein expression was enhanced and p-PKC isoforms were significantly down-regulated by luteolin treatment in a dose-dependent manner, and a similar effect was observed upon DPI treatment. However, co-treatment with the specific inhibitor of AMPK (Compound C) restored p-PKC levels suggesting the role of AMPK signaling in regulating p-PKC expression under oxidative stress condition in HUVECs. Finally, we confirmed using siRNAs and specific inhibitor and/or activator of AMPK (AICAR) that luteolin treatment induced AMPK is a key player and regulator of activated expression of PKC isoforms and thereby confers protection against H 2 O 2 -induced oxidative stress in HUVECs.
Type of Medium:
Online Resource
ISSN:
0192-415X
,
1793-6853
DOI:
10.1142/S0192415X19500289
Language:
English
Publisher:
World Scientific Pub Co Pte Ltd
Publication Date:
2019
