Berberine reduces leukocyte adhesion to LPS-stimulated endothelial cells and VCAM-1 expression both in vivo and in vitro.
Leukocyte adhesion to endothelium plays a critical initiating role in inflammation. Berberine, an anti-inflammatory natural compound, is known to attenuate lipopolysaccharide (LPS)-induced lung injury and improve survival of endotoxemic animals with mechanism not fully clarified. This study investigated the effects of berberine on the LPS-induced leukocyte-endothelial cell adhesion both in vivo and in vitro. We first established an animal model to observe the in vivo LPS-induced adhesion of leukocytes to the endothelium of venules in the lung tissue dose-dependently. Pretreatment of LPS-stimulated rats with berberine for 1 h reduced the leukocyte-endothelium adhesion and vascular cell adhesion molecule-1 (VCAM-1) expression in lung. Pretreatment of LPS-stimulated vascular endothelial cells with berberine also dose-dependently decreased the number of adhered THP-1 cells and VCAM-1 expression at both RNA and protein levels. Berberine was further confirmed to inhibit the nuclear translocation and DNA binding activity of LPS-activated nuclear factor-kappa B (NF-kappa B). These data demonstrated an additional molecular mechanism for the profound anti-inflammatory effect of berberine.
Graduate Institute of Clinical Medical Sciences, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan, R.O.C.
Y-H
YH
Wu
S-Y
SY
Chuang
W-C
WC
Hong
Y-J
YJ
Lai
G-J
GJ
Chang
J-H S
JH
Pang
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001599:Berberine / Q000494:pharmacology*; D001665:Binding Sites; D002448:Cell Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D042783:Endothelial Cells / Q000187:drug effects* / Q000276:immunology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000276:immunology; D007962:Leukocytes / Q000187:drug effects* / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000098:blood supply*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D014699:Venules / Q000187:drug effects* / Q000276:immunology
D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D001599:Berberine; D004247:DNA