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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

Honokiol regulated the expression of PTX3 and inflammatory response in PA-induced HUVECs model. PTX-3 levels from the enzyme-linked immunosorbent assay (ELISA) (a), western blotting (b) and reverse-transcriptase PCR (RT-PCR) (c) in HUVECs after treatment with vehicle, 0.5 mM PA, PA plus 10 μM honokiol or PA plus an inhibitor of IKK-2 (TPCA-1, 30 μM) for 48 h. (d) Protein expression of IkB and p-IkB in HUVECs after treatment with vehicle, 0.5 mM PA or PA plus 10 μM honokiol for 48 h. (e) Protein expression of p50 and p65 in HUVECs after treatment with vehicle, 0.5 mM PA or PA plus 10 μM honokiol for 48 h. (f) IL-6, IL-8 and MCP-1 levels measured by the ELISA assay in HUVECs after treatment with vehicle, 0.5 mM PA or PA plus 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 and ##P<0.01, versus 0.5 mM PA treatment group.
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fig3: Honokiol regulated the expression of PTX3 and inflammatory response in PA-induced HUVECs model. PTX-3 levels from the enzyme-linked immunosorbent assay (ELISA) (a), western blotting (b) and reverse-transcriptase PCR (RT-PCR) (c) in HUVECs after treatment with vehicle, 0.5 mM PA, PA plus 10 μM honokiol or PA plus an inhibitor of IKK-2 (TPCA-1, 30 μM) for 48 h. (d) Protein expression of IkB and p-IkB in HUVECs after treatment with vehicle, 0.5 mM PA or PA plus 10 μM honokiol for 48 h. (e) Protein expression of p50 and p65 in HUVECs after treatment with vehicle, 0.5 mM PA or PA plus 10 μM honokiol for 48 h. (f) IL-6, IL-8 and MCP-1 levels measured by the ELISA assay in HUVECs after treatment with vehicle, 0.5 mM PA or PA plus 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 and ##P<0.01, versus 0.5 mM PA treatment group.

Mentions: PA caused dysfunction in HUVECs and led to overexpression of PTX3. However, the regulatory mechanism of PTX3 expression in PA-inducted HUVECs remains unclear. The NF-κB pathway has been shown to have an important role in the inflammatory response, especially in tumorigenesis caused by chronic inflammation.42, 43 To understand the possible mechanism behind PTX3 overexpression in a PA-induced atherosclerosis model, we incubated HUVECs with PA (0.5 mM), PA plus an inhibitor of IKK-2 (TPCA-1, 30 μM) or PA plus honokiol (10 μM) for 48 h. From enzyme-linked immunosorbent assay analysis, quantitative reverse-transcriptase PCR and western blotting, we observed an obvious increase of PTX3 in HUVECs after PA treatment (P<0.05, Figures 3a, b and c). In addition, TPCA-1, an inhibitor of IKK-2, significantly suppressed the upregulation of PTX3 induced by PA (P<0.01). Similarly, honokiol significantly inhibited the ectopic expression of PTX3 in HUVECs (P<0.01).


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)

Honokiol regulated the expression of PTX3 and inflammatory response in PA-induced HUVECs model. PTX-3 levels from the enzyme-linked immunosorbent assay (ELISA) (a), western blotting (b) and reverse-transcriptase PCR (RT-PCR) (c) in HUVECs after treatment with vehicle, 0.5 mM PA, PA plus 10 μM honokiol or PA plus an inhibitor of IKK-2 (TPCA-1, 30 μM) for 48 h. (d) Protein expression of IkB and p-IkB in HUVECs after treatment with vehicle, 0.5 mM PA or PA plus 10 μM honokiol for 48 h. (e) Protein expression of p50 and p65 in HUVECs after treatment with vehicle, 0.5 mM PA or PA plus 10 μM honokiol for 48 h. (f) IL-6, IL-8 and MCP-1 levels measured by the ELISA assay in HUVECs after treatment with vehicle, 0.5 mM PA or PA plus 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 and ##P<0.01, versus 0.5 mM PA treatment group.
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fig3: Honokiol regulated the expression of PTX3 and inflammatory response in PA-induced HUVECs model. PTX-3 levels from the enzyme-linked immunosorbent assay (ELISA) (a), western blotting (b) and reverse-transcriptase PCR (RT-PCR) (c) in HUVECs after treatment with vehicle, 0.5 mM PA, PA plus 10 μM honokiol or PA plus an inhibitor of IKK-2 (TPCA-1, 30 μM) for 48 h. (d) Protein expression of IkB and p-IkB in HUVECs after treatment with vehicle, 0.5 mM PA or PA plus 10 μM honokiol for 48 h. (e) Protein expression of p50 and p65 in HUVECs after treatment with vehicle, 0.5 mM PA or PA plus 10 μM honokiol for 48 h. (f) IL-6, IL-8 and MCP-1 levels measured by the ELISA assay in HUVECs after treatment with vehicle, 0.5 mM PA or PA plus 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 and ##P<0.01, versus 0.5 mM PA treatment group.
Mentions: PA caused dysfunction in HUVECs and led to overexpression of PTX3. However, the regulatory mechanism of PTX3 expression in PA-inducted HUVECs remains unclear. The NF-κB pathway has been shown to have an important role in the inflammatory response, especially in tumorigenesis caused by chronic inflammation.42, 43 To understand the possible mechanism behind PTX3 overexpression in a PA-induced atherosclerosis model, we incubated HUVECs with PA (0.5 mM), PA plus an inhibitor of IKK-2 (TPCA-1, 30 μM) or PA plus honokiol (10 μM) for 48 h. From enzyme-linked immunosorbent assay analysis, quantitative reverse-transcriptase PCR and western blotting, we observed an obvious increase of PTX3 in HUVECs after PA treatment (P<0.05, Figures 3a, b and c). In addition, TPCA-1, an inhibitor of IKK-2, significantly suppressed the upregulation of PTX3 induced by PA (P<0.01). Similarly, honokiol significantly inhibited the ectopic expression of PTX3 in HUVECs (P<0.01).

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