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Celastrol nanoparticles inhibit corneal neovascularization induced by suturing in rats.

Li Z, Yao L, Li J, Zhang W, Wu X, Liu Y, Lin M, Su W, Li Y, Liang D - Int J Nanomedicine (2012)

Bottom Line: In vivo, suture-induced CNV was chosen to evaluate the effect of CNPs on CNV in rats.After treatment with CNPs, the length and area of CNV reduced from 1.16 ± 0.18 mm to 0.49 ± 0.12 mm and from 7.71 ± 0.94 mm(2) to 2.29 ± 0.61 mm(2), respectively.Macrophage infiltration decreased significantly in the CNP-treated corneas.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, People's Republic of China.

ABSTRACT

Purpose: Celastrol, a traditional Chinese medicine, is widely used in anti-inflammation and anti-angiogenesis research. However, the poor water solubility of celastrol restricts its further application. This paper aims to study the effect of celastrol nanoparticles (CNPs) on corneal neovascularization (CNV) and determine the possible mechanism.

Methods: To improve the hydrophilicity of celastrol, celastrol-loaded poly(ethylene glycol)-block-poly(ɛ-caprolactone) nanopolymeric micelles were developed. The characterization of CNPs was measured by dynamic light scattering and transmission electron microscopy analysis. Celastrol loading content and release were assessed by ultraviolet-visible analysis and high performance liquid chromatography, respectively. In vitro, human umbilical vein endothelial cell proliferation and capillary-like tube formation were assayed. In vivo, suture-induced CNV was chosen to evaluate the effect of CNPs on CNV in rats. Immunohistochemistry for CD68 assessed the macrophage infiltration of the cornea on day 6 after surgery. Real-time quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay were used to evaluate the messenger ribonucleic acid and protein levels, respectively, of vascular endothelial growth factor, matrix metalloproteinase 9, and monocyte chemoattractant protein 1 in the cornea.

Results: The mean diameter of CNPs with spherical shape was 48 nm. The celastrol loading content was 7.36%. The release behavior of CNPs in buffered solution (pH 7.4) showed a typical two-phase release profile. CNPs inhibited the proliferation of human umbilical vein endothelial cells in a dose-independent manner and suppressed the capillary structure formation. After treatment with CNPs, the length and area of CNV reduced from 1.16 ± 0.18 mm to 0.49 ± 0.12 mm and from 7.71 ± 0.94 mm(2) to 2.29 ± 0.61 mm(2), respectively. Macrophage infiltration decreased significantly in the CNP-treated corneas. CNPs reduced the expression of vascular endothelial growth factor, matrix metalloproteinase 9, and monocyte chemoattractant protein 1 in the cornea on day 6 after suturing.

Conclusion: CNPs significantly inhibited suture-induced CNV by suppressing macrophage infiltration and the expression of vascular endothelial growth factor and matrix metalloproteinase 9 in the rat cornea.

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Celastrol nanoparticles inhibit the expression of angiogenic genes. Corneas were harvested on day 6 after surgery, followed by messenger ribonucleic acid expression analysis using real-time reverse transcription-polymerase chain reaction. Normal corneas were used as the control. Messenger ribonucleic acid expression of vascular endothelial growth factor, matrix metalloproteinase 9, and monocyte chemoattractant protein 1 in the normal corneas were arbitrarily set as 1.0. The y-axis shows the mean of the relative messenger ribonucleic acid expression of a certain gene compared to the normal cornea gene. Celastrol nanoparticles decreased the expression of (A) vascular endothelial growth factor, (B) matrix metalloproteinase 9, and (C) monocyte chemoattractant protein 1 messenger ribonucleic acid in the cornea on day 6 after surgery.Notes: The data are presented as mean ± standard deviation. Statistical significance is based on the difference when compared with the control; *P < 0.001.Abbreviations: CNPs, celastrol nanoparticles; MCP-1, monocyte chemoattractant protein 1; MMP-9, matrix metalloproteinase 9; VEGF, vascular endothelial growth factor.
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f7-ijn-7-1163: Celastrol nanoparticles inhibit the expression of angiogenic genes. Corneas were harvested on day 6 after surgery, followed by messenger ribonucleic acid expression analysis using real-time reverse transcription-polymerase chain reaction. Normal corneas were used as the control. Messenger ribonucleic acid expression of vascular endothelial growth factor, matrix metalloproteinase 9, and monocyte chemoattractant protein 1 in the normal corneas were arbitrarily set as 1.0. The y-axis shows the mean of the relative messenger ribonucleic acid expression of a certain gene compared to the normal cornea gene. Celastrol nanoparticles decreased the expression of (A) vascular endothelial growth factor, (B) matrix metalloproteinase 9, and (C) monocyte chemoattractant protein 1 messenger ribonucleic acid in the cornea on day 6 after surgery.Notes: The data are presented as mean ± standard deviation. Statistical significance is based on the difference when compared with the control; *P < 0.001.Abbreviations: CNPs, celastrol nanoparticles; MCP-1, monocyte chemoattractant protein 1; MMP-9, matrix metalloproteinase 9; VEGF, vascular endothelial growth factor.

Mentions: To further study the effect of CNPs on CNV, quantitative real-time reverse transcription-PCR was performed to determine the relative mRNA expression of VEGF, MMP-9, and MCP-1 on day 6 after surgery in rat corneas. Normal corneas were used as the control. The mRNA expression of the normal corneas was arbitrarily set as 1.0. As shown in Figure 7, CNPs significantly decreased the mRNA expression of VEGF, MMP-9, and MCP-1 in the cornea (P < 0.001). When compared with the control, a significant decrease in the expressions of VEGF (5.89-fold versus 1.69-fold) and MCP-1 (10.11-fold versus 3.90-fold) and a moderate decrease in MMP-9 (4.97-fold versus 2.35-fold) were observed in the CNP treatment group.


Celastrol nanoparticles inhibit corneal neovascularization induced by suturing in rats.

Li Z, Yao L, Li J, Zhang W, Wu X, Liu Y, Lin M, Su W, Li Y, Liang D - Int J Nanomedicine (2012)

Celastrol nanoparticles inhibit the expression of angiogenic genes. Corneas were harvested on day 6 after surgery, followed by messenger ribonucleic acid expression analysis using real-time reverse transcription-polymerase chain reaction. Normal corneas were used as the control. Messenger ribonucleic acid expression of vascular endothelial growth factor, matrix metalloproteinase 9, and monocyte chemoattractant protein 1 in the normal corneas were arbitrarily set as 1.0. The y-axis shows the mean of the relative messenger ribonucleic acid expression of a certain gene compared to the normal cornea gene. Celastrol nanoparticles decreased the expression of (A) vascular endothelial growth factor, (B) matrix metalloproteinase 9, and (C) monocyte chemoattractant protein 1 messenger ribonucleic acid in the cornea on day 6 after surgery.Notes: The data are presented as mean ± standard deviation. Statistical significance is based on the difference when compared with the control; *P < 0.001.Abbreviations: CNPs, celastrol nanoparticles; MCP-1, monocyte chemoattractant protein 1; MMP-9, matrix metalloproteinase 9; VEGF, vascular endothelial growth factor.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3298384&req=5

f7-ijn-7-1163: Celastrol nanoparticles inhibit the expression of angiogenic genes. Corneas were harvested on day 6 after surgery, followed by messenger ribonucleic acid expression analysis using real-time reverse transcription-polymerase chain reaction. Normal corneas were used as the control. Messenger ribonucleic acid expression of vascular endothelial growth factor, matrix metalloproteinase 9, and monocyte chemoattractant protein 1 in the normal corneas were arbitrarily set as 1.0. The y-axis shows the mean of the relative messenger ribonucleic acid expression of a certain gene compared to the normal cornea gene. Celastrol nanoparticles decreased the expression of (A) vascular endothelial growth factor, (B) matrix metalloproteinase 9, and (C) monocyte chemoattractant protein 1 messenger ribonucleic acid in the cornea on day 6 after surgery.Notes: The data are presented as mean ± standard deviation. Statistical significance is based on the difference when compared with the control; *P < 0.001.Abbreviations: CNPs, celastrol nanoparticles; MCP-1, monocyte chemoattractant protein 1; MMP-9, matrix metalloproteinase 9; VEGF, vascular endothelial growth factor.
Mentions: To further study the effect of CNPs on CNV, quantitative real-time reverse transcription-PCR was performed to determine the relative mRNA expression of VEGF, MMP-9, and MCP-1 on day 6 after surgery in rat corneas. Normal corneas were used as the control. The mRNA expression of the normal corneas was arbitrarily set as 1.0. As shown in Figure 7, CNPs significantly decreased the mRNA expression of VEGF, MMP-9, and MCP-1 in the cornea (P < 0.001). When compared with the control, a significant decrease in the expressions of VEGF (5.89-fold versus 1.69-fold) and MCP-1 (10.11-fold versus 3.90-fold) and a moderate decrease in MMP-9 (4.97-fold versus 2.35-fold) were observed in the CNP treatment group.

Bottom Line: In vivo, suture-induced CNV was chosen to evaluate the effect of CNPs on CNV in rats.After treatment with CNPs, the length and area of CNV reduced from 1.16 ± 0.18 mm to 0.49 ± 0.12 mm and from 7.71 ± 0.94 mm(2) to 2.29 ± 0.61 mm(2), respectively.Macrophage infiltration decreased significantly in the CNP-treated corneas.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, People's Republic of China.

ABSTRACT

Purpose: Celastrol, a traditional Chinese medicine, is widely used in anti-inflammation and anti-angiogenesis research. However, the poor water solubility of celastrol restricts its further application. This paper aims to study the effect of celastrol nanoparticles (CNPs) on corneal neovascularization (CNV) and determine the possible mechanism.

Methods: To improve the hydrophilicity of celastrol, celastrol-loaded poly(ethylene glycol)-block-poly(ɛ-caprolactone) nanopolymeric micelles were developed. The characterization of CNPs was measured by dynamic light scattering and transmission electron microscopy analysis. Celastrol loading content and release were assessed by ultraviolet-visible analysis and high performance liquid chromatography, respectively. In vitro, human umbilical vein endothelial cell proliferation and capillary-like tube formation were assayed. In vivo, suture-induced CNV was chosen to evaluate the effect of CNPs on CNV in rats. Immunohistochemistry for CD68 assessed the macrophage infiltration of the cornea on day 6 after surgery. Real-time quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay were used to evaluate the messenger ribonucleic acid and protein levels, respectively, of vascular endothelial growth factor, matrix metalloproteinase 9, and monocyte chemoattractant protein 1 in the cornea.

Results: The mean diameter of CNPs with spherical shape was 48 nm. The celastrol loading content was 7.36%. The release behavior of CNPs in buffered solution (pH 7.4) showed a typical two-phase release profile. CNPs inhibited the proliferation of human umbilical vein endothelial cells in a dose-independent manner and suppressed the capillary structure formation. After treatment with CNPs, the length and area of CNV reduced from 1.16 ± 0.18 mm to 0.49 ± 0.12 mm and from 7.71 ± 0.94 mm(2) to 2.29 ± 0.61 mm(2), respectively. Macrophage infiltration decreased significantly in the CNP-treated corneas. CNPs reduced the expression of vascular endothelial growth factor, matrix metalloproteinase 9, and monocyte chemoattractant protein 1 in the cornea on day 6 after suturing.

Conclusion: CNPs significantly inhibited suture-induced CNV by suppressing macrophage infiltration and the expression of vascular endothelial growth factor and matrix metalloproteinase 9 in the rat cornea.

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Related in: MedlinePlus