Anti-inflammatory mechanisms of apigenin: inhibition of cyclooxygenase-2 expression, adhesion of monocytes to human umbilical vein endothelial cells, and expression of cellular adhesion molecules.
The aim of this study was to clarify the anti-inflammatory mechanism of apigenin. Apigenin inhibited the collagenase activity involved in rheumatoid arthritis (RA) and suppressed lipopolysaccharide (LPS)-induced nitric oxide (NO) production in a dose dependent manner in RAW 264.7 macrophage cells. Pretreatment with apigenin also attenuated LPS-induced cyclooxygenase-2 (COX-2) expression. In addition, apigenin profoundly reduced the tumor necrosis factor-alpha (TNF-alpha)-induced adhesion of monocytes to HUVEC monolayer. Apigenin significantly suppressed the TNF-alpha-stimulated upregulation of vascular cellular adhesion molecule-1 (VCAM-1)-, intracellular adhesion molecule-1 (ICAM-1)-, and E-selectin-mRNA to the basal levels. Taken together, these results suggest that apigenin has significant anti-inflammatory activity that involves blocking NO-mediated COX-2 expression and monocyte adherence. These results further suggest that apigenin may be useful for therapeutic management of inflammatory diseases.
Plant Resources Research Institute, Duksung Women's University Seoul 132-714, Korea.
Je-Hyuk
JH
Lee
Hong Yu
HY
Zhou
So Yean
SY
Cho
Yeong Shik
YS
Kim
Yong Soo
YS
Lee
Choon Sik
CS
Jeong
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D047310:Apigenin / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D017364:Collagenases / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014471:Umbilical Veins / Q000187:drug effects / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D000975:Antioxidants; D015815:Cell Adhesion Molecules; D052246:Cyclooxygenase 2 Inhibitors; D019040:E-Selectin; D008070:Lipopolysaccharides; D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; D047310:Apigenin; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D006821:Hyaluronoglucosaminidase; D017364:Collagenases