Andrographolide inhibits nuclear factor- B activation through JNK-Akt-p65 signaling cascade in tumor necrosis factor- α -Stimulated vascular smooth muscle cells

Yu Ying Chen, Ming Jen Hsu, Cheng Ying Hsieh, Lin Wen Lee, Zhih Cherng Chen, Joen Rong Sheu

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Critical vascular inflammation leads to vascular dysfunction and cardiovascular diseases, including abdominal aortic aneurysms, hypertension, and atherosclerosis. Andrographolide is the most active and critical constituent isolated from the leaves of Andrographis paniculata, a herbal medicine widely used for treating anti-inflammation in Asia. In this study, we investigated the mechanisms of the inhibitory effects of andrographolide in vascular smooth muscle cells (VSMCs) exposed to a proinflammatory stimulus, tumor necrosis factor-α (TNF-α). Treating TNF-α-stimulated VSMCs with andrographolide suppressed the expression of inducible nitric oxide synthase in a concentration-dependent manner. A reduction in TNF-α-induced c-Jun N-terminal kinase (JNK), Akt, and p65 phosphorylation was observed in andrographolide-treated VSMCs. However, andrographolide affected neither IBα degradation nor p38 mitogen-activated protein kinase or extracellular signal-regulated kinase 1/2 phosphorylation under these conditions. Both treatment with LY294002, a phosphatidylinositol 3-kinase/Akt inhibitor, and treatment with SP600125, a JNK inhibitor, markedly reversed the andrographolide-mediated inhibition of p65 phosphorylation. In addition, LY294002 and SP600125 both diminished Akt phosphorylation, whereas LY294002 had no effects on JNK phosphorylation. These results collectively suggest that therapeutic interventions using andrographolide can benefit the treatment of vascular inflammatory diseases, and andrographolide-mediated inhibition of NF-B activity in TNF-α-stimulated VSMCs occurs through the JNK-Akt-p65 signaling cascade, an IBα-independent mechanism.

Original languageEnglish
Article number130381
Number of pages10
JournalScientific World Journal
Volume2014
DOIs
Publication statusPublished - 2014

Fingerprint

JNK Mitogen-Activated Protein Kinases
Vascular Smooth Muscle
tumor
Smooth Muscle Myocytes
Muscle
muscle
Tumor Necrosis Factor-alpha
Phosphorylation
Chemical activation
Cells
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
inhibitor
hypertension
cardiovascular disease
nitric oxide
Vascular Diseases
Andrographis
Phosphatidylinositol 3-Kinase
Inflammation
degradation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Environmental Science(all)
  • Medicine(all)

Cite this

@article{72312b4489a44a639bc75ba259c6aa3b,
title = "Andrographolide inhibits nuclear factor- B activation through JNK-Akt-p65 signaling cascade in tumor necrosis factor- α -Stimulated vascular smooth muscle cells",
abstract = "Critical vascular inflammation leads to vascular dysfunction and cardiovascular diseases, including abdominal aortic aneurysms, hypertension, and atherosclerosis. Andrographolide is the most active and critical constituent isolated from the leaves of Andrographis paniculata, a herbal medicine widely used for treating anti-inflammation in Asia. In this study, we investigated the mechanisms of the inhibitory effects of andrographolide in vascular smooth muscle cells (VSMCs) exposed to a proinflammatory stimulus, tumor necrosis factor-α (TNF-α). Treating TNF-α-stimulated VSMCs with andrographolide suppressed the expression of inducible nitric oxide synthase in a concentration-dependent manner. A reduction in TNF-α-induced c-Jun N-terminal kinase (JNK), Akt, and p65 phosphorylation was observed in andrographolide-treated VSMCs. However, andrographolide affected neither IBα degradation nor p38 mitogen-activated protein kinase or extracellular signal-regulated kinase 1/2 phosphorylation under these conditions. Both treatment with LY294002, a phosphatidylinositol 3-kinase/Akt inhibitor, and treatment with SP600125, a JNK inhibitor, markedly reversed the andrographolide-mediated inhibition of p65 phosphorylation. In addition, LY294002 and SP600125 both diminished Akt phosphorylation, whereas LY294002 had no effects on JNK phosphorylation. These results collectively suggest that therapeutic interventions using andrographolide can benefit the treatment of vascular inflammatory diseases, and andrographolide-mediated inhibition of NF-B activity in TNF-α-stimulated VSMCs occurs through the JNK-Akt-p65 signaling cascade, an IBα-independent mechanism.",
author = "Chen, {Yu Ying} and Hsu, {Ming Jen} and Hsieh, {Cheng Ying} and Lee, {Lin Wen} and Chen, {Zhih Cherng} and Sheu, {Joen Rong}",
year = "2014",
doi = "10.1155/2014/130381",
language = "English",
volume = "2014",
journal = "The Scientific World Journal",
issn = "2356-6140",
publisher = "Hindawi Publishing Corporation",

}

TY - JOUR

T1 - Andrographolide inhibits nuclear factor- B activation through JNK-Akt-p65 signaling cascade in tumor necrosis factor- α -Stimulated vascular smooth muscle cells

AU - Chen, Yu Ying

AU - Hsu, Ming Jen

AU - Hsieh, Cheng Ying

AU - Lee, Lin Wen

AU - Chen, Zhih Cherng

AU - Sheu, Joen Rong

PY - 2014

Y1 - 2014

N2 - Critical vascular inflammation leads to vascular dysfunction and cardiovascular diseases, including abdominal aortic aneurysms, hypertension, and atherosclerosis. Andrographolide is the most active and critical constituent isolated from the leaves of Andrographis paniculata, a herbal medicine widely used for treating anti-inflammation in Asia. In this study, we investigated the mechanisms of the inhibitory effects of andrographolide in vascular smooth muscle cells (VSMCs) exposed to a proinflammatory stimulus, tumor necrosis factor-α (TNF-α). Treating TNF-α-stimulated VSMCs with andrographolide suppressed the expression of inducible nitric oxide synthase in a concentration-dependent manner. A reduction in TNF-α-induced c-Jun N-terminal kinase (JNK), Akt, and p65 phosphorylation was observed in andrographolide-treated VSMCs. However, andrographolide affected neither IBα degradation nor p38 mitogen-activated protein kinase or extracellular signal-regulated kinase 1/2 phosphorylation under these conditions. Both treatment with LY294002, a phosphatidylinositol 3-kinase/Akt inhibitor, and treatment with SP600125, a JNK inhibitor, markedly reversed the andrographolide-mediated inhibition of p65 phosphorylation. In addition, LY294002 and SP600125 both diminished Akt phosphorylation, whereas LY294002 had no effects on JNK phosphorylation. These results collectively suggest that therapeutic interventions using andrographolide can benefit the treatment of vascular inflammatory diseases, and andrographolide-mediated inhibition of NF-B activity in TNF-α-stimulated VSMCs occurs through the JNK-Akt-p65 signaling cascade, an IBα-independent mechanism.

AB - Critical vascular inflammation leads to vascular dysfunction and cardiovascular diseases, including abdominal aortic aneurysms, hypertension, and atherosclerosis. Andrographolide is the most active and critical constituent isolated from the leaves of Andrographis paniculata, a herbal medicine widely used for treating anti-inflammation in Asia. In this study, we investigated the mechanisms of the inhibitory effects of andrographolide in vascular smooth muscle cells (VSMCs) exposed to a proinflammatory stimulus, tumor necrosis factor-α (TNF-α). Treating TNF-α-stimulated VSMCs with andrographolide suppressed the expression of inducible nitric oxide synthase in a concentration-dependent manner. A reduction in TNF-α-induced c-Jun N-terminal kinase (JNK), Akt, and p65 phosphorylation was observed in andrographolide-treated VSMCs. However, andrographolide affected neither IBα degradation nor p38 mitogen-activated protein kinase or extracellular signal-regulated kinase 1/2 phosphorylation under these conditions. Both treatment with LY294002, a phosphatidylinositol 3-kinase/Akt inhibitor, and treatment with SP600125, a JNK inhibitor, markedly reversed the andrographolide-mediated inhibition of p65 phosphorylation. In addition, LY294002 and SP600125 both diminished Akt phosphorylation, whereas LY294002 had no effects on JNK phosphorylation. These results collectively suggest that therapeutic interventions using andrographolide can benefit the treatment of vascular inflammatory diseases, and andrographolide-mediated inhibition of NF-B activity in TNF-α-stimulated VSMCs occurs through the JNK-Akt-p65 signaling cascade, an IBα-independent mechanism.

UR - http://www.scopus.com/inward/record.url?scp=84904607592&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84904607592&partnerID=8YFLogxK

U2 - 10.1155/2014/130381

DO - 10.1155/2014/130381

M3 - Article

C2 - 25114952

AN - SCOPUS:84904607592

VL - 2014

JO - The Scientific World Journal

JF - The Scientific World Journal

SN - 2356-6140

M1 - 130381

ER -