Induction of Heme Oxygenase 1 and Inhibition of Tumor Necrosis Factor α-Induced Intercellular Adhesion Molecule Expression by Andrographolide in EA.hy926 Cells
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- 作者：Ai-Lin Yu ; Chia-Yang Lu ; Tsu-Shing Wang ; Chia-Wen Tsai ; Kai-Li Liu ; Yi-Ping Cheng ; Hebron C. Chang ; Chong-Kuei Lii ; Haw-Wen Chen
- 刊名：Journal of Agricultural and Food Chemistry
- 出版年：2010
- 出版时间：July 14, 2010
- 年：2010
- 卷：58
- 期：13
- 页码：7641-7648
- 全文大小：851K
- 年卷期：v.58,no.13(July 14, 2010)
- ISSN：1520-5118
文摘
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 α (TNF-α) in EA.hy926 cells and the possible mechanisms involved. Andrographolide (2.5−7.5 μM) inhibited the TNF-α-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-α-induced ICAM-1 expression exerted by andrographolide.