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

Abstract

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.

Sulforaphane Inhibits TNF-α-Induced Adhesion Molecule Expression Through the Rho A/ROCK/NF-κB Signaling Pathway

“…Apigenin profoundly blocked monocyte adhesion to the monolayer of human umbilical vein endothelial cells (HUVECs) by suppressing TNF-a-stimulated upregulation of VCAM-1, ICAM-1, and E-selectin mRNA expression. 47 Curcumin also decreased the intracellular ROS levels, phosphorylation of JNK, p38, and STAT3, and the expression of ICAM-1, MCP-1, IL-8, and lectin-like oxidized LDL receptor-1 (LOX-1) in TNF-a-stimulated HUVECs. 48,49 In the present study, pretreatment with SFN inhibited significantly NF-jB-induced IL-1, IL-6, IL8, and ICAM expressions, indicating that SFN has similar antiinflammatory and vasoprotective properties.…”

Puerarin Inhibits Adhesion Molecule Expression in TNF-α-Stimulated Human Endothelial Cells via Modulation of the Nuclear Factor ĸB Pathway

“…Inflammation-related genes such as adhesion cells contain binding sites for a number of important transcription factors, including NF-B [15,16] . Increase in adhesion cell gene expression is associated with inflammatory response which has been linked to the development of autoimmune disorders, coronary artery disease and cancer [17,18] . In this study, the results indicated that puerarin inhibited the expression of the protein and mRNA levels of ICAM-1, VCAM-1 and Eselectin in TNF-␣ -induced HUVECs.…”

Ischemic Neurodegeneration in Stroke-Prone Spontaneously Hypertensive Rats and Its Prevention with Antioxidants Such as Polyphenols

“…On the other hand, it has been shown that stimulation of expression of endothelial NOS (eNOS) by apigenin occurs through phosphatidylinositol 3-kinase/Akt (PI3K/Akt) for Ca 2+ dependence . Moreover, the blockade of adhesion of monocytes and cyclooxygenase (COX)-2 expression in endothelial cells by apigenin has been reported (Lee et al, 2007). We have shown that apigenin strongly inhibits high glucose-and TNF--induced VCAM1 expression and the adhesion of U937 in human endothelial cells (Yamagata et al, 2010b).…”