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

Qiu L, Xu R, Wang S, Li S, Sheng H, Wu J, Qu Y - Exp. Mol. Med. (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Geriatrics Department, Shanghai Clinical Center, Chinese Academy of Sciences/Shanghai Xuhui Central Hospital, Shanghai, China.

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.

No MeSH data available.


Related in: MedlinePlus

PA-induced HUVECs injury. (a) Cell viability of HUVECs after treatment with various concentrations of PA for 24 or 48 h. (b) Cell viability of HUVECs after treatment with various concentrations of honokiol for 24 or 48 h. (c) Apoptosis of HUVECs after treatment with vehicle, 0.5 mM PA, 1 mM PA or 10 μM honokiol for 48 h. Data are mean±s.d., n=3 in each group. *P<0.05, versus untreated group. #P<0.05, versus 0.5 mM PA treatment group.
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fig1: PA-induced HUVECs injury. (a) Cell viability of HUVECs after treatment with various concentrations of PA for 24 or 48 h. (b) Cell viability of HUVECs after treatment with various concentrations of honokiol for 24 or 48 h. (c) Apoptosis of HUVECs after treatment with vehicle, 0.5 mM PA, 1 mM PA or 10 μM honokiol for 48 h. Data are mean±s.d., n=3 in each group. *P<0.05, versus untreated group. #P<0.05, versus 0.5 mM PA treatment group.

Mentions: To investigate PA-induced injury of HUVECs, we incubated the HUVECs with different concentrations of PA. The viability of HUVECs incubated with different concentrations of PA for 24 or 48 h was determined using CCK-8 assays. The results showed that PA treatment induced cell death in a concentration-dependent and time-dependent manner (Figure 1a). To investigate whether PA induced cell death through an apoptotic mechanism, annexin V/propidium iodide double staining was used to detect early apoptosis. As shown in Figure 1c, the early apoptotic rate significantly increased in HUVECs after 48 h of PA exposure at doses of 0.5 and 1 mM (P<0.05). Finally, we investigated the level of PTX3 in HUVECs with PA treatment. The quantitative reverse-transcriptase PCR and western blot analyses showed that the expression level of mRNA and protein for PTX3 significantly increased in the PA treatment group compared with the control (Figure 2a). In addition, immunochemistry exhibited an enhanced PTX3 signal in HUVECs after PA treatment (Figure 2b).


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

Qiu L, Xu R, Wang S, Li S, Sheng H, Wu J, Qu Y - Exp. Mol. Med. (2015)

PA-induced HUVECs injury. (a) Cell viability of HUVECs after treatment with various concentrations of PA for 24 or 48 h. (b) Cell viability of HUVECs after treatment with various concentrations of honokiol for 24 or 48 h. (c) Apoptosis of HUVECs after treatment with vehicle, 0.5 mM PA, 1 mM PA or 10 μM honokiol for 48 h. Data are mean±s.d., n=3 in each group. *P<0.05, versus untreated group. #P<0.05, versus 0.5 mM PA treatment group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4525296&req=5

fig1: PA-induced HUVECs injury. (a) Cell viability of HUVECs after treatment with various concentrations of PA for 24 or 48 h. (b) Cell viability of HUVECs after treatment with various concentrations of honokiol for 24 or 48 h. (c) Apoptosis of HUVECs after treatment with vehicle, 0.5 mM PA, 1 mM PA or 10 μM honokiol for 48 h. Data are mean±s.d., n=3 in each group. *P<0.05, versus untreated group. #P<0.05, versus 0.5 mM PA treatment group.
Mentions: To investigate PA-induced injury of HUVECs, we incubated the HUVECs with different concentrations of PA. The viability of HUVECs incubated with different concentrations of PA for 24 or 48 h was determined using CCK-8 assays. The results showed that PA treatment induced cell death in a concentration-dependent and time-dependent manner (Figure 1a). To investigate whether PA induced cell death through an apoptotic mechanism, annexin V/propidium iodide double staining was used to detect early apoptosis. As shown in Figure 1c, the early apoptotic rate significantly increased in HUVECs after 48 h of PA exposure at doses of 0.5 and 1 mM (P<0.05). Finally, we investigated the level of PTX3 in HUVECs with PA treatment. The quantitative reverse-transcriptase PCR and western blot analyses showed that the expression level of mRNA and protein for PTX3 significantly increased in the PA treatment group compared with the control (Figure 2a). In addition, immunochemistry exhibited an enhanced PTX3 signal in HUVECs after PA treatment (Figure 2b).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Geriatrics Department, Shanghai Clinical Center, Chinese Academy of Sciences/Shanghai Xuhui Central Hospital, Shanghai, China.

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.

No MeSH data available.


Related in: MedlinePlus