Inhibition of TNF-α-Induced Inflammation by andrographolide via down-regulation of the PI3K/Akt signaling pathway.

Abstract

Andrographolide (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.

• Authors: 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 Liu
• Journal: Journal of natural products (J Nat Prod) Vol. 74 Issue 11 Pg. 2408-13 (Nov 28 2011) ISSN: 1520-6025 [Electronic] United States
• PMID: 22026410 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Chromones
• Diterpenes
• Morpholines
• NF-kappa B
• Tumor Necrosis Factor-alpha
• Intercellular Adhesion Molecule-1
• 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
• andrographolide
• DNA
• Proto-Oncogene Proteins c-akt

Topics

• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Cell Survival (drug effects)
• Chromones (pharmacology)
• DNA (drug effects, metabolism)
• Diterpenes (chemistry, pharmacology)
• Down-Regulation
• HL-60 Cells
• Human Umbilical Vein Endothelial Cells (drug effects)
• Humans
• Intercellular Adhesion Molecule-1 (drug effects, genetics, metabolism)
• Molecular Structure
• Morpholines (pharmacology)
• NF-kappa B (drug effects, metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Tumor Necrosis Factor-alpha (antagonists & inhibitors)