np200631v_si_001.pdf (426.65 kB)
Inhibition of TNF-α-Induced Inflammation by Andrographolide via Down-Regulation of the PI3K/Akt Signaling Pathway
journal contribution
posted on 2016-02-22, 13:14 authored by Haw-Wen Chen, Ai-Hsuan Lin, Hsing-Chin Chu, Chien-Chun Li, Chia-Wen Tsai, Che-Yi Chao, Chau-Jong Wang, Chong-Kuei Lii, Kai-Li LiuAndrographolide (1), an active constituent
of Andrographis paniculata, decreased tumor necrosis
factor-α
(TNF-α)-induced intercellular adhesion molecule-1 (ICAM-1) expression
and adhesion of HL-60 cells onto human umbilical vein endothelial
cells (HUVEC), which are associated with inflammatory diseases. Moreover, 1 abolished TNF-α-induced Akt phosphorylation. Transfection
of an activated Akt1 cDNA vector increased Akt phosphorylation and
ICAM-1 expression like TNF-α. In addition, 1 and
LY294002 blocked TNF-α-induced IκB-α degradation
and nuclear p65 protein accumulation, as well as the DNA-binding activity
of NF-κB. Compound 1 exhibits anti-inflammatory
properties through the inhibition of TNF-α-induced ICAM-1 expression.
The anti-inflammatory activity of 1 may be associated
with the inhibition of the PI3K/Akt pathway and downstream target
NF-κB activation in HUVEC cells.