Exp Mol Med.  2015 Jul;47(7):e171. 10.1038/emm.2015.37.

Honokiol ameliorates endothelial dysfunction through suppression of PTX3 expression, a key mediator of IKK/IkappaB/NF-kappaB, in atherosclerotic cell model

• Qiu L
• Xu R
• Wang S
• Li S
• Sheng H
• Wu J
• Qu Y

• KMID: 2155425
• DOI: http://doi.org/10.1038/emm.2015.37

Abstract

Pentraxin 3 (PTX3) was identified as a marker of the inflammatory response and overexpressed in various tissues and cells related to cardiovascular disease. Honokiol, an active component isolated from the Chinese medicinal herb Magnolia officinalis, was shown to have a variety of pharmacological activities. In the present study, we aimed to investigate the effects of honokiol on palmitic acid (PA)-induced dysfunction of human umbilical vein endothelial cells (HUVECs) and to elucidate potential regulatory mechanisms in this atherosclerotic cell model. Our results showed that PA significantly accelerated the expression of PTX3 in HUVECs through the IkappaB kinase (IKK)/IkappaB/nuclear factor-kappaB (NF-kappaB) pathway, reduced cell viability, induced cell apoptosis and triggered the inflammatory response. Knockdown of PTX3 supported cell growth and prevented apoptosis by blocking PA-inducted nitric oxide (NO) overproduction. Honokiol significantly suppressed the overexpression of PTX3 in PA-inducted HUVECs by inhibiting IkappaB phosphorylation and the expression of two NF-kappaB subunits (p50 and p65) in the IKK/IkappaB/NF-kappaB signaling pathway. Furthermore, honokiol reduced endothelial cell injury and apoptosis by regulating the expression of inducible NO synthase and endothelial NO synthase, as well as the generation of NO. Honokiol showed an anti-inflammatory effect in PA-inducted HUVECs by significantly inhibiting the generation of interleukin-6 (IL-6), IL-8 and monocyte chemoattractant protein-1. In summary, honokiol repaired endothelial dysfunction by suppressing PTX3 overexpression in an atherosclerotic cell model. PTX3 may be a potential therapeutic target for atherosclerosis.

MeSH Terms

Apoptosis/drug effects
Atherosclerosis/chemically induced/*drug therapy/immunology/pathology
Biphenyl Compounds/chemistry/isolation & purification/*pharmacology
C-Reactive Protein/*genetics/immunology
Down-Regulation/drug effects
Drugs, Chinese Herbal/chemistry/isolation & purification/*pharmacology
Human Umbilical Vein Endothelial Cells
Humans
I-kappa B Kinase/*immunology
Lignans/chemistry/isolation & purification/*pharmacology
Magnolia/chemistry
Palmitic Acid
Protein-Serine-Threonine Kinases/*immunology
Serum Amyloid P-Component/*genetics/immunology
Signal Transduction/drug effects
Biphenyl Compounds
Drugs, Chinese Herbal
Lignans
Serum Amyloid P-Component
Palmitic Acid
C-Reactive Protein
Protein-Serine-Threonine Kinases
I-kappa B Kinase