Leonurine attenuates lipopolysaccharide-induced inflammatory responses in human endothelial cells: involvement of reactive oxygen species and NF-κB pathways.
Leonurine, an active alkaloid of Traditional Chinese Medicine Herba leonuri, displayed cardioprotective effects by anti-oxidative and anti-apoptotic activities in vitro and in vivo. Herein, we explored the effects and possible mechanisms of leonurine on lipopolysaccharide (LPS)-induced inflammatory responses in human umbilical vein endothelial cells (HUVEC). We found that leonurine pretreatment concentration-dependently attenuated LPS-induced mRNA expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and monocyte chemoattractant protein-1. Meanwhile, LPS-mediated expression/release of ICAM-1, VCAM-1, and cyclooxygenase-2, and tumor necrosis factor-α was also reduced by leonurine. In addition, we confirmed that leonurine suppressed degradation of IκBα and phosphorylation of nuclear factor-κB (NF-κB) p65 as well as production of intracellular reactive oxygen species in a concentration dependent manner. Furthermore, the cytoprotective enzyme heme oxygenase-1 could be upregulated in leonurine-treated HUVEC. Our present results indicated leonurine exerted beneficial effects in inflammatory conditions partly through inhibition of reactive oxygen species and NF-κB signaling pathways.
Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China.
Xin Hua
XH
Liu
Li Long
LL
Pan
He Bei
HB
Yang
Qi Hai
QH
Gong
Yi Zhun
YZ
Zhu
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D018932:Chemokine CCL2; D019040:E-Selectin; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C013587:leonurine; D018799:Intercellular Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha; D005707:Gallic Acid; D051547:Heme Oxygenase-1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human