PMID- 30966772 OWN - NLM STAT- MEDLINE DCOM- 20191017 LR - 20191017 IS - 1793-6853 (Electronic) IS - 0192-415X (Linking) VI - 47 IP - 3 DP - 2019 TI - Luteolin: A Natural Flavonoid Enhances the Survival of HUVECs against Oxidative Stress by Modulating AMPK/PKC Pathway. PG - 541-557 LID - 10.1142/S0192415X19500289 [doi] AB - 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. FAU - Ou, Hsiu-Chung AU - Ou HC AD - * Department of Occupational Therapy, College of Medical and Health Science, Taichung, Taiwan. FAU - Pandey, Sudhir AU - Pandey S AD - double dagger Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan. FAU - Hung, Meng-Yu AU - Hung MY AD - section sign Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan. FAU - Huang, Su-Hua AU - Huang SH AD - dagger Department of Biotechnology, Asia University, Taichung, Taiwan. FAU - Hsu, Pei-Tz AU - Hsu PT AD - dagger Department of Biotechnology, Asia University, Taichung, Taiwan. FAU - Day, Cecilia-Hsuan AU - Day CH AD - ** Department of Nursing, Meiho University, Pingtung, Taiwan. FAU - Pai, Peiying AU - Pai P AD - paragraph sign School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan. AD - daggerdagger Division of Cardiovascular Medicine, Department of Medicine, China Medical University Hospital, Taichung, Taiwan. FAU - Viswanadha, Vijaya Padma AU - Viswanadha VP AD - section sign section sign Department of Biotechnology, Bharathiar University, Coimbatore, India. FAU - Kuo, Wei-Wen AU - Kuo WW AD - parallel Department of Biological Science and Technology, China Medical University, Taichung, Taiwan. FAU - Huang, Chih-Yang AU - Huang CY AD - double dagger Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan. AD - section sign Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan. AD - double daggerdouble dagger Medical Research Center For Exosomes and Mitochondria Related Diseases, China Medical University Hospital, Taichung, Taiwan. AD - paragraph sign paragraph sign Department of Clinical Laboratory, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangdong, China. AD - parallel parallel College of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien, Taiwan. LA - eng PT - Journal Article DEP - 20190409 PL - Singapore TA - Am J Chin Med JT - The American journal of Chinese medicine JID - 7901431 RN - 0 (Flavonoids) RN - BBX060AN9V (Hydrogen Peroxide) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) RN - KUX1ZNC9J2 (Luteolin) SB - IM MH - AMP-Activated Protein Kinases/metabolism MH - Cell Survival/*drug effects MH - Cells, Cultured MH - Flavonoids/*pharmacology MH - Human Umbilical Vein Endothelial Cells/*metabolism MH - Humans MH - Hydrogen Peroxide/adverse effects MH - Luteolin/*pharmacology MH - MAP Kinase Signaling System/*drug effects MH - Oxidative Stress/*drug effects OTO - NOTNLM OT - AMPK OT - HUVECs OT - Luteolin OT - NADPH Oxidase OT - PKC OT - ROS EDAT- 2019/04/11 06:00 MHDA- 2019/10/18 06:00 CRDT- 2019/04/11 06:00 PHST- 2019/04/11 06:00 [pubmed] PHST- 2019/10/18 06:00 [medline] PHST- 2019/04/11 06:00 [entrez] AID - 10.1142/S0192415X19500289 [doi] PST - ppublish SO - Am J Chin Med. 2019;47(3):541-557. doi: 10.1142/S0192415X19500289. Epub 2019 Apr 9.