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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

Effect of PTX3 knockdown on PA-induced HUVECs model. (a) Protein expression of iNOS and eNOS, and (b) NO concentration in HUVECs after treatment with vehicle, 0.5 mM PA, PA plus 10 μM honokiol or si-PTX3 plus 0.5 mM PA for 48 h. (c) The cell viability and (d) apoptosis of HUVECs after treatment with vehicle, 0.5 mM PA, PA plus 10 μM honokiol or si-PTX3 plus 0.5 mM PA for 48 h. Data are mean±s.d., n=3 in each group. *P<0.05, **P<0.01, versus untreated group. #P<0.05, ##P<0.01, versus 0.5 mM PA treatment group.
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fig4: Effect of PTX3 knockdown on PA-induced HUVECs model. (a) Protein expression of iNOS and eNOS, and (b) NO concentration in HUVECs after treatment with vehicle, 0.5 mM PA, PA plus 10 μM honokiol or si-PTX3 plus 0.5 mM PA for 48 h. (c) The cell viability and (d) apoptosis of HUVECs after treatment with vehicle, 0.5 mM PA, PA plus 10 μM honokiol or si-PTX3 plus 0.5 mM PA for 48 h. Data are mean±s.d., n=3 in each group. *P<0.05, **P<0.01, versus untreated group. #P<0.05, ##P<0.01, versus 0.5 mM PA treatment group.

Mentions: In HUVECs, PA upregulated PTX3 expression, suppressed cell growth and induced cell apoptosis. To investigate the role of PTX3 in PA-induced HUVECs apoptosis, we blocked PTX3 with small interfering RNA. After treatment with PA (0.5 mM), eNOS expression significantly decreased and iNOS expression increased compared with the untreated group (P<0.05, Figure 4a). Accordingly, NO production also increased (P<0.05, Figure 4b). Knockdown of PTX3 led to a significant rise of eNOS and a reduction in iNOS, as well as a significant reduction in NO secretion (P<0.05, Figures 4a and b). The results of the cell viability and apoptosis analyses showed that knockdown of PTX3 repaired cell growth and blocked cell apoptosis induced by PA (Figures 4c and d). Collectively, these results suggest that PTX3 was one of the targets of PA-induced apoptosis. A potential regulation mechanism was that PTX3 inhibited eNOS expression and activated iNOS expression, thereby promoting the overproduction of NO in HVECs and eventually leading to apoptosis.


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)

Effect of PTX3 knockdown on PA-induced HUVECs model. (a) Protein expression of iNOS and eNOS, and (b) NO concentration in HUVECs after treatment with vehicle, 0.5 mM PA, PA plus 10 μM honokiol or si-PTX3 plus 0.5 mM PA for 48 h. (c) The cell viability and (d) apoptosis of HUVECs after treatment with vehicle, 0.5 mM PA, PA plus 10 μM honokiol or si-PTX3 plus 0.5 mM PA for 48 h. Data are mean±s.d., n=3 in each group. *P<0.05, **P<0.01, versus untreated group. #P<0.05, ##P<0.01, versus 0.5 mM PA treatment group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig4: Effect of PTX3 knockdown on PA-induced HUVECs model. (a) Protein expression of iNOS and eNOS, and (b) NO concentration in HUVECs after treatment with vehicle, 0.5 mM PA, PA plus 10 μM honokiol or si-PTX3 plus 0.5 mM PA for 48 h. (c) The cell viability and (d) apoptosis of HUVECs after treatment with vehicle, 0.5 mM PA, PA plus 10 μM honokiol or si-PTX3 plus 0.5 mM PA for 48 h. Data are mean±s.d., n=3 in each group. *P<0.05, **P<0.01, versus untreated group. #P<0.05, ##P<0.01, versus 0.5 mM PA treatment group.
Mentions: In HUVECs, PA upregulated PTX3 expression, suppressed cell growth and induced cell apoptosis. To investigate the role of PTX3 in PA-induced HUVECs apoptosis, we blocked PTX3 with small interfering RNA. After treatment with PA (0.5 mM), eNOS expression significantly decreased and iNOS expression increased compared with the untreated group (P<0.05, Figure 4a). Accordingly, NO production also increased (P<0.05, Figure 4b). Knockdown of PTX3 led to a significant rise of eNOS and a reduction in iNOS, as well as a significant reduction in NO secretion (P<0.05, Figures 4a and b). The results of the cell viability and apoptosis analyses showed that knockdown of PTX3 repaired cell growth and blocked cell apoptosis induced by PA (Figures 4c and d). Collectively, these results suggest that PTX3 was one of the targets of PA-induced apoptosis. A potential regulation mechanism was that PTX3 inhibited eNOS expression and activated iNOS expression, thereby promoting the overproduction of NO in HVECs and eventually leading to apoptosis.

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