Luteolin: A Natural Flavonoid Enhances the Survival of HUVECs against Oxidative Stress by Modulating AMPK/PKC Pathway

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 (H2O2). Our results showed that luteolin protected against H2O2-induced oxidative stress and ameliorated ROS and superoxide generation. In addition, we found that luteolin treatment inhibited the H2O2-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 H2O2-induced oxidative stress in HUVECs.

Honey and Its Phenolic Compounds as an Effective Natural Medicine for Cardiovascular Diseases in Humans?

“…They note that daily supplementation with 100 mg/kg and 200 mg/kg luteolin reduced high blood pressure and oxidative stress, including lipid peroxidation (expressed as MDA) and protein carbonylation, among 40 male Wistar albino rats. Another study by Ou et al [82] found luteolin to have antioxidant potential against various parameters of oxidative stress, to protect against oxidative stress induced by hydrogen peroxide, a hydrogen radical donor, and reduce the production of ROS in human umbilical vein endothelial cells (HUVECs). The authors propose that luteolin may exert its effects through the regulation of protein kinase C. Luteolin has also been found to display inhibitory effects on the proliferation and migration of vascular smooth muscle cells, suggesting that it may also be a potential candidate for preventing and treating atherosclerosis [83].…”

The Rediscovery of Honey for Skin Repair: Recent Advances in Mechanisms for Honey-Mediated Wound Healing and Scaffolded Application Techniques

“…Reports of using honey and its related bee products (propolis, beeswax, pollen) in traditional medicine stretch back centuries, since the first reports from Sumer, and then in ancient Egypt, Greece, Rome, and Asia [5], due to their appreciated and renowned health benefits. However, despite the many hypotheses on the mechanisms for the numerous beneficial effects, honey's full potential has started to be unlocked only recently, with more comprehensive characterisations of its physicochemical composition (as described in Section 2 of this paper), and the further investigation of the medical activity of natural bioactive compounds also found in honey [6][7][8][9][10][11][12][13][14][15]. Honey has been shown to possess beneficial properties with diverse applications in otorhinolaryngology [16,17], respiratory tract diseases [18,19], cardiovascular diseases [20][21][22], metabolic disorders [23][24][25][26], oncology [27,28].…”

Natural Antioxidants: A Review of Studies on Human and Animal Coronavirus

“…Luteolin is present in foods such as carrot, cabbage, tea, and apple and is found in Ugni molinae Turcz. [ 73 , 74 ]. Data show that luteolin (50 μ g/mL) increases the levels of GSH, the expression of GSH synthetase, and the activity of SOD and CAT in human colon cancer cells (HT-29) [ 75 ].…”