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

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 IκB kinase (IKK)/IκB/nuclear factor-κB (NF-κB) 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 IκB phosphorylation and the expression of two NF-κB subunits (p50 and p65) in the IKK/IκB/NF-κB 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. A chemical found in magnolia bark suppresses the activity of inflammatory molecules and helps repair the inner lining of blood vessels. A magnolia tree extract called honokiol is widely used in traditional Chinese medicine to treat a range of ailments. Yi Qu and colleagues from the Shanghai Clinical Center, China, tested the effects of honokiol in a cellular model of atherosclerosis. The researchers cultured human umbilical vein endothelial cells with a fatty acid known to induce cell injury. They added honokiol and observed lower levels of several molecules involved in inflammatory responses, including pentraxin 3 (PTX3). Honokiol treatment or direct experimental reduction of PTX3 levels decreased the expression of damaging free radicals and protected against cell death. The authors propose a mechanism for honokiol activity and suggest that PTX3 provides a potential drug target for treating atherosclerosis.