Yu AL, Lu CY, Wang TS, Tsai CW, Liu KL, Cheng YP, Chang HC, Lii CK, Chen HW.
Department of Nutrition, China Medical University, Taichung, Taiwan.
Andrographolide is the most abundant diterpene lactone in Andrographis
paniculata, which is widely used as a traditional medicine in
Southeast Asia. Heme oxygenase 1 (HO-1) is an antioxidant enzyme
encoded by a stress-responsive gene. HO-1 has been reported to inhibit
the expression of adhesion molecules in vascular endothelial cells
(EC). Intercellular adhesion molecule (ICAM-1) is an inflammatory
biomarker that is involved in the adhesion of monocytes to EC. In this
study, we investigated the effect of andrographolide on the expression
of ICAM-1 induced by tumor necrosis factor alpha (TNF-alpha) in
EA.hy926 cells and the possible mechanisms involved. Andrographolide
(2.5-7.5 muM) inhibited the TNF-alpha-induced expression of ICAM-1 in
a dose-dependent manner and resulted in a decrease in HL-60 cell
adhesion to EA.hy926 cells (p < 0.05). In parallel, andrographolide
significantly induced the expression of HO-1 in a
concentration-dependent fashion (p < 0.05). Andrographolide increased
the rate of nuclear translocation of nuclear factor erythroid
2-related 2 (Nrf2) and induced antioxidant response element-luciferase
reporter activity. Transfection with HO-1-specific small interfering
RNA knocked down HO-1 expression, and the inhibition of expression of
ICAM-1 by andrographolide was significantly reversed. These results
suggest that stimulation of Nrf2-dependent HO-1 expression is involved
in the suppression of TNF-alpha-induced ICAM-1 expression exerted by
andrographolide.
PMID: 20536138 [PubMed - as supplied by publisher]
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