curcumin and Corneal-Neovascularization

This study was to investigate the anti-angiogenic effect of hexahydrocurcumin (HHC) to evaluate gene (p-basic fibroblast growth factor (bFGF)-SAINT-18 & p-vascular endothelial growth factor (VEGF)-SAINT-18 complex)-induced corneal neovascularization (CorNV) in rats.. CorNV was induced in 24 eyes of 24 rats. Four groups (Group A: 0 μg, B: 0.01 μg, C: 0.1 μg, and D: 1 μg) of HHC were prepared and implanted into the rat subconjunctival substantia propria 1.5 mm from the limbus at temporal side. The 1 μg of p-bFGF-SAINT-18 & p-VEGF-SAINT-18 complex were prepared and implanted into the rat corneal stroma 1.5 mm from the limbus at the same side. Inhibition of CorNV was observed and quantified from day 1 to day 60. bFGF and VEGF protein expression were analyzed by biomicroscopic examination, western blot analysis, and immunohistochemistry.. Subconjunctival injection by 1 μg HHC successfully inhibited gene-induced CorNV in rats. bFGF and VEGF protein expression were reduced after 6 days. Meanwhile, the reduction of HLA-DR expression was detected.. Our study showed that the HHC might provide an important anti-angiogenesis factor to inhibit CorNV development at the corneal experimental angiogenesis model.

Topics: Angiogenesis Inhibitors; Animals; Blotting, Western; Conjunctiva; Corneal Neovascularization; Curcumin; Disease Models, Animal; Fibroblast Growth Factor 2; HLA-DR Antigens; Male; Rats; Rats, Sprague-Dawley; Vascular Endothelial Growth Factor A

Curcumin (capable of inhibiting angiogenic growth of human umbilical vein endothelial cells [HUVECs]), can be employed in vitro as a model of pathogenesis of corneal neovascularization (CRNV). The aim of this study was to explore regulatory mechanisms of microRNA (miR) levels after curcumin treatment.. Expression profiles of miRs in curcumin-treated HUVECs were investigated by miR microassay. Specific mimics and inhibitors of miR-1275 or miR-1246 were transfected into HUVECs. Then, their target genes, vascular endothelial growth factor B (VEGFB) and nuclear transcription factor kappa B acting protein (NKAP) were detected by quantitative real-time PCR, Western blotting assay or immunofluorescence assay. Cell proliferation and cell cycle parameters were measured with the help of CCK-8 assay and flow cytometry.. MiR-1275 and miR-1246 expression levels were up-regulated by curcumin. Administration of the specific mimics and inhibitors of the two miRs led to significant changes in expression of VEGFB and NKAP as well as the indicators related to angiogenesis. Anti-angiogenic effect of curcumin depended on expression patterns of the two miRs in that inhibition of either miR interfered with the effect of curcumin. Furthermore, overexpression of NKAP interrupted effects of curcumin on the cells.. Collectively, our findings demonstrate that curcumin inhibited HUVEC proliferation by up-regulation of miR-1275 and miR-1246.

Topics: Angiogenesis Inhibitors; Co-Repressor Proteins; Corneal Neovascularization; Curcumin; Human Umbilical Vein Endothelial Cells; Humans; MicroRNAs; Neovascularization, Pathologic; Nuclear Proteins; Repressor Proteins; Up-Regulation

Corneal neovascularization is a leading cause for compromised vision. Therapeutic prevention of corneal neovascularization is a major clinical challenge, and there is a compelling need to seek effective and safe therapy for this pathology. This study is aimed to evaluate curcumin nanoparticle for prevention of corneal neovascularization. MePEG-PCL nanoparticles were successfully prepared and characterized. The nanoparticle of curcumin has shown increased efficiency in preventing angiogenic sprouting in vitro. Topical delivery of curcumin nanoparticle in the eye showed enhanced retention of curcumin in the cornea, and significant improvement in prevention of corneal neovascularization over free curcumin as graded clinically and by histopathology; suppression in the expression of VEGF, inflammatory cytokines, and MMP was evidenced in the treated cornea. Curcumin inhibited NFκB in LPS-induced corneal cells. Histopathology and scanning electron microscopy showed absence of any adverse change in the corneal structure following application of curcumin nanoparticle. Therefore, we conclude that curcumin nanoparticle can be a potential candidate for prevention of corneal neovascularization.. • Curcumin nanoparticles show enhanced retention of curcumin in the cornea. • Curcumin NPs suppress the expression of VEGF, inflammatory cytokines, and MMP. • Curcumin NPs prevent corneal neovascularization by suppressing the NFκB pathway. • Curcumin NPs may be a promising candidate for prevention of corneal neovascularization.

Topics: Angiogenesis Inhibitors; Animals; Aorta, Thoracic; Cells, Cultured; Cornea; Corneal Keratocytes; Corneal Neovascularization; Curcumin; Drug Carriers; Female; I-kappa B Proteins; Interleukin-1beta; Lipopolysaccharides; Male; Mice; Nanoparticles; NF-kappa B; NF-KappaB Inhibitor alpha; Polyesters; Polyethylene Glycols; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A

To investigate the anti-angiogenic effect of topical curcumin on corneal neovascularization in a rabbit model.. One week after suturing, six eyes were treated with balanced salt solution (BSS) (group A), and six eyes were treated with curcumin 40, 80, or 160 micromol/L (groups B, C, and D, respectively), topically two times a day. After one week, light microscopy was used to analyze corneal neovascularization. The concentration of vascular endothelial growth factor (VEGF) mRNA in the corneal tissue was measured by reverse transcriptase-polymerase chain reaction (RT-PCR), and the activation of NF-kappaB was examined by immunofluorescent staining.. Seven days after treatment, the sizes of the neovascularized areas were significantly reduced in groups B (50.1% +/- 6.7%), C (43.2% +/- 8.1%), and D (29.5% +/- 7.8%) compared with group A (69.5% +/- 1.5%) (p < 0.05). The corneal VEGF mRNA levels were significantly lower in groups C and D than they were in group A (p < 0.05). Immunofluorescent staining showed that phospho-NF-kappaB staining of the corneal tissue was weaker in group C than it was in groups A and B.. Topical application of curcumin was useful in reducing experimental corneal neovascularization and can be used to inhibit angiogenesis in the cornea.

Topics: Administration, Topical; Angiogenesis Inhibitors; Animals; Corneal Neovascularization; Curcumin; Disease Models, Animal; Fluorescent Antibody Technique, Indirect; Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating); NF-kappa B; Ophthalmic Solutions; Rabbits; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Vascular Endothelial Growth Factor A

To examine the effect of curcumin on the proliferation and the migration of human umbilical vein endothelial cells (HUVECs) and on the corneal neovascularization in the corneal alkaline burn rat model.. HUVEC proliferation, migration, and apoptosis were examined after treatment with various concentrations of curcumin. The effect of curcumin on the activation of nuclear factor-kappaB (NF-kappaB) was measured by an electrophoretic mobility shift assay (EMSA) in vivo. Corneal neovascularization was induced in vivo by an alkaline burn of the cornea in Sprague-Dawley rats. After topical drug treatments with curcumin, vascular endothelial growth factor (VEGF) was evaluated in the corneal tissue by reverse transcription polymerase chain reaction and by immunohistochemistry. Corneal neovascularization was evaluated by slit-lamp biomicroscopy.. Curcumin at a concentration of 40 micromol/l for 24 h significantly inhibited the growth of HUVECs. The Boyden microchamber assay showed that curcumin dramatically inhibited the migration of HUVECs at a concentration of 40 micromol/l. When TUNEL assays were performed, the number of apoptotic cells increased after treated with curcumin. The EMSA revealed that curcumin inhibits the activation of NF-kappaB in HUVECs. The expression of VEGF in the corneal tissues was inhibited by curcumin on days 7 and 14 after alkaline burn.. Curcumin may be useful as an angiogenic inhibitor in the treatment of corneal diseases that show neovascularization.

Topics: Alkalies; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Movement; Cell Proliferation; Cells, Cultured; Corneal Neovascularization; Curcumin; Disease Models, Animal; Electrophoretic Mobility Shift Assay; Gene Expression; Humans; Immunohistochemistry; In Situ Nick-End Labeling; Male; Neovascularization, Pathologic; Ophthalmic Solutions; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA; Treatment Outcome; Umbilical Veins; Vascular Endothelial Growth Factor A

Curcumin is a small-molecular-weight compound that is isolated from the commonly used spice turmeric. In animal models, curcumin and its derivatives have been shown to inhibit the progression of chemically induced colon and skin cancers. The genetic changes in carcinogenesis in these organs involve different genes, but curcumin is effective in preventing carcinogenesis in both organs. A possible explanation for this finding is that curcumin may inhibit angiogenesis.. Curcumin was tested for its ability to inhibit the proliferation of primary endothelial cells in the presence and absence of basic fibroblast growth factor (bFGF), as well as its ability to inhibit proliferation of an immortalized endothelial cell line. Curcumin and its derivatives were subsequently tested for their ability to inhibit bFGF-induced corneal neovascularization in the mouse cornea. Finally, curcumin was tested for its ability to inhibit phorbol ester-stimulated vascular endothelial growth factor (VEGF) mRNA production.. Curcumin effectively inhibited endothelial cell proliferation in a dose-dependent manner. Curcumin and its derivatives demonstrated significant inhibition of bFGF-mediated corneal neovascularization in the mouse. Curcumin had no effect on phorbol ester-stimulated VEGF production.. These results indicate that curcumin has direct antiangiogenic activity in vitro and in vivo. The activity of curcumin in inhibiting carcinogenesis in diverse organs such as the skin and colon may be mediated in part through angiogenesis inhibition.

Topics: Angiogenesis Inhibitors; Animals; Antineoplastic Agents; Cattle; Cell Differentiation; Cell Line, Transformed; Corneal Neovascularization; Curcumin; Endothelial Growth Factors; Endothelium, Vascular; Enzyme Activation; Enzyme Inhibitors; Fibroblast Growth Factor 2; Keratinocytes; Lymphokines; Male; Mice; Mice, Inbred C57BL; NAD(P)H Dehydrogenase (Quinone); Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors