Protective effects of luteolin against oxidative stress and mitochondrial dysfunction in endothelial cells

被引:54
作者
Chen, Hsiu-, I [1 ]
Hu, Wei-Syun [2 ]
Hung, Meng-Yu [3 ]
Ou, Hsiu-Chung [4 ]
Huang, Su-Hua [5 ]
Hsu, Pei-Tzu [5 ]
Day, Cecilia-Hsuan [6 ]
Lin, Kuan-Ho [2 ,7 ]
Viswanadha, Vijaya P. [8 ]
Kuo, Wei-Wen [9 ]
Huang, Chih-Yang [3 ,5 ,10 ,11 ,12 ]
机构
[1] Hungkuang Univ, Dept Phys Therapy, Taichung, Taiwan
[2] China Med Univ, Coll Med, Sch Med, Taichung 40402, Taiwan
[3] China Med Univ & Hosp, Grad Inst Biomed, Taichung, Taiwan
[4] Asia Univ, Coll Med & Hlth Sci, Dept Phys Therapy, Taichung, Taiwan
[5] Asia Univ, Dept Biotechnol, Taichung, Taiwan
[6] Meiho Univ, Dept Nursing, Pingtung, Taiwan
[7] China Med Univ Hosp, Dept Med, Div Emergency, Taichung 40447, Taiwan
[8] Bharathiar Univ, Dept Biotechnol, Coimbatore 641046, Tamil Nadu, India
[9] China Med Univ, Dept Biol Sci & Technol, Taichung, Taiwan
[10] China Med Univ, China Med Univ Hosp, Dept Med Res, Taichung 404, Taiwan
[11] Buddhist Tzu Chi Med Fdn, Hualien Tzu Chi Hosp, Cardiovasc & Mitochondrial Related Dis Res Ctr, Hualien, Taiwan
[12] Tzu Chi Univ Sci & Technol, Buddhist Tzu Chi Med Fdn, Ctr Gen Educ, Hualien 970, Taiwan
关键词
Luteolin; oxLDL; Apoptosis; Oxidative stress; Mitochondrial dysfunction; ACTIVATED PROTEIN-KINASE; MAPK/NF-KAPPA-B; INDUCED APOPTOSIS; PROGENITOR CELLS; INFLAMMATION; INHIBITION; PATHWAYS; CALCIUM; MACROPHAGES; INJURY;
D O I
10.1016/j.numecd.2020.02.014
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background and aims: Luteolin is a common flavonoid that is abundantly present in various edible plants, it is known to exhibit beneficial effects on cardiovascular system. However, the mechanisms which underlie the protective effects of luteolin on endothelial cell damage caused by oxidative stress remains unclear. The purpose of this study is to test the hypothesis which states that luteolin protects against H2O2-induced oxidative stress via modulating ROS-mediated P38 MAPK/NF-kappa B and calcium-evoked mitochondrial apoptotic signalling pathways. Methods and results: Human umbilical vein endothelial cells (HUVECs) were pretreated with luteolin prior to being stimulated by 600 mu M H2O2 for another 24 h. The expression of native and phosphorylated-P38, I kappa B, NF-kappa B, native eNOS, phosphorylated-eNOS, iNOS and several apoptosis-related proteins were analyzed by Western blot. In addition, intracellular calcium was determined by fura-2 AM and mitochondrial membrane potential was examined by using JC1. Using the data gathered, we found indications that H2O2 induced P38 MAPK/NF-kappa B activation. H2O2 downregulated the expression of eNOS and upregulated iNOS, which in turn contribute to an elevated NO generation and protein nitrosylation. However, pretreatment with luteolin markedly reversed all of these alterations dose-dependently. Additionally, an intracellular calcium rise and subsequent mitochondrial membrane potential collapse, P53 phosphorylation, reduced BcL-2/Bax ratio in the mitochondrial membrane, release cytochrome c from mitochondria, leading to the subsequent activation of caspase 3 activation by H2O2 were all markedly suppressed in the presence of luteolin. Conclusion: Results from this study may provide the possible molecular mechanisms underlying cardiovascular protective effects of luteolin. (C) 2020 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:1032 / 1043
页数:12
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