Inhibitory effects of safranal on laser-induced choroidal neovascularization and human choroidal microvascular endothelial cells and related pathways analyzed with transcriptome sequencing
AIM: To determine the effects of safranal on choroidal neovascularization (CNV) and oxidative stress damage of human choroidal microvascular endothelial cells (HCVECs) and its possible mechanisms. METHODS: Forty-five rats were used as a laser-induced CNV model for testing the efficacy and safety of...
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| Format: | Article |
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Press of International Journal of Ophthalmology (IJO PRESS)
2021-07-01
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| Series: | International Journal of Ophthalmology |
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| Online Access: | http://ies.ijo.cn/en_publish/2021/7/20210704.pdf |
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| author | Qin-Xiao Yao-Yao Sun Zhan-Jun Lu Tian-Zi Zhang Shan-Shan Li Ting Hua Suriguga Wen-Lin Chen Lin-Lin Ran Wen-Zhen Yu Fei Yang Burenbatu |
| author_facet | Qin-Xiao Yao-Yao Sun Zhan-Jun Lu Tian-Zi Zhang Shan-Shan Li Ting Hua Suriguga Wen-Lin Chen Lin-Lin Ran Wen-Zhen Yu Fei Yang Burenbatu |
| author_sort | Qin-Xiao |
| collection | DOAJ |
| description | AIM: To determine the effects of safranal on choroidal neovascularization (CNV) and oxidative stress damage of human choroidal microvascular endothelial cells (HCVECs) and its possible mechanisms. METHODS: Forty-five rats were used as a laser-induced CNV model for testing the efficacy and safety of safranal (0.5 mg/kg·d, intraperitoneally) on CNV. CNV leakage on fluorescein angiography (FA) and CNV thickness on histology was compared. HCVECs were used for a H2O2-induced oxidative stress model to test the effect of safranal in vitro. MTT essay was carried to test the inhibition rate of safranal on cell viability at different concentrations. Tube formation was used to test protective effect of safranal on angiogenesis at different concentrations. mRNA transcriptome sequencing was performed to find the possible signal pathway. The expressions of different molecules and their phosphorylation level were validated by Western blotting. RESULTS: On FA, the average CNV leakage area was 0.73±0.49 and 0.31±0.11 mm2 (P?=?0.012) in the control and safranal-treated group respectively. The average CNV thickness was 127.4±18.75 and 100.6±17.34 μm (P=0.001) in control and safranal-treated group. Under the condition of oxidative stress, cell proliferation was inhibited by safranal and inhibition rates were 7.4%-35.4% at the different concentrations. For tube formation study, the number of new branches was 364 in control group and 35, 42, and 17 in 20, 40, and 80 μg/mL safranal groups respectively (P<0.01). From the KEGG pathway bubble graph, the PI3K-AKT signaling pathway showed a high gene ratio. The protein expression was elevated of insulin receptor substrate (IRS) and the phosphorylation level of PI3K, phosphoinositide-dependent protein kinase 1/2 (PDK1/2), AKT and Bcl-2 associated death promoter (BAD) was also elevated under oxidative stress condition but inhibited by safranal. CONCLUSION: Safranal can inhibit CNV both in vivo and in vitro, and the IRS-PI3K-PDK1/2-AKT-BAD signaling pathway is involved in the pathogenesis of CNV. |
| first_indexed | 2024-12-17T07:08:40Z |
| format | Article |
| id | doaj.art-15ad60dcb0964aafbb63dc9cfef1de43 |
| institution | Directory Open Access Journal |
| issn | 2222-3959 2227-4898 |
| language | English |
| last_indexed | 2024-12-17T07:08:40Z |
| publishDate | 2021-07-01 |
| publisher | Press of International Journal of Ophthalmology (IJO PRESS) |
| record_format | Article |
| series | International Journal of Ophthalmology |
| spelling | doaj.art-15ad60dcb0964aafbb63dc9cfef1de432022-12-21T21:59:06ZengPress of International Journal of Ophthalmology (IJO PRESS)International Journal of Ophthalmology2222-39592227-48982021-07-0114798198910.18240/ijo.2021.07.0420210704Inhibitory effects of safranal on laser-induced choroidal neovascularization and human choroidal microvascular endothelial cells and related pathways analyzed with transcriptome sequencingQin-Xiao0Yao-Yao Sun1Zhan-Jun Lu2Tian-Zi Zhang3Shan-Shan Li4Ting Hua5Suriguga6Wen-Lin Chen7Lin-Lin Ran8Wen-Zhen Yu9Fei Yang10Burenbatu11Burenbatu. Department of Hematology, Affiliated Hospital of Inner Mongolia University for Nationalities, No.1742 East Huolinhe Avenue, Tongliao 028007, Inner Mongolia Autonomous Region, China. dr_burenbatu@126.comDepartment of Ophthalmology, Peking University People's Hospital, Beijing100044, ChinaDepartment of Ophthalmology, Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao 028007, Inner Mongolia Autonomous Region, ChinaDepartment of Ophthalmology, Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao 028007, Inner Mongolia Autonomous Region, ChinaDepartment of Ophthalmology, Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao 028007, Inner Mongolia Autonomous Region, ChinaCollege of Mongolian Medicine, Inner Mongolia University for Nationalities, Tongliao 028000, Inner Mongolia Autonomous Region, ChinaCollege of Mongolian Medicine, Inner Mongolia University for Nationalities, Tongliao 028000, Inner Mongolia Autonomous Region, ChinaCollege of Mongolian Medicine, Inner Mongolia University for Nationalities, Tongliao 028000, Inner Mongolia Autonomous Region, ChinaCollege of Mongolian Medicine, Inner Mongolia University for Nationalities, Tongliao 028000, Inner Mongolia Autonomous Region, ChinaDepartment of Ophthalmology, Peking University People's Hospital, Beijing100044, ChinaDepartment of Ophthalmology, Peking University International Hospital, Beijing 100026, ChinaDepartment of Hematology, Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao 028007, Inner Mongolia Autonomous Region, ChinaAIM: To determine the effects of safranal on choroidal neovascularization (CNV) and oxidative stress damage of human choroidal microvascular endothelial cells (HCVECs) and its possible mechanisms. METHODS: Forty-five rats were used as a laser-induced CNV model for testing the efficacy and safety of safranal (0.5 mg/kg·d, intraperitoneally) on CNV. CNV leakage on fluorescein angiography (FA) and CNV thickness on histology was compared. HCVECs were used for a H2O2-induced oxidative stress model to test the effect of safranal in vitro. MTT essay was carried to test the inhibition rate of safranal on cell viability at different concentrations. Tube formation was used to test protective effect of safranal on angiogenesis at different concentrations. mRNA transcriptome sequencing was performed to find the possible signal pathway. The expressions of different molecules and their phosphorylation level were validated by Western blotting. RESULTS: On FA, the average CNV leakage area was 0.73±0.49 and 0.31±0.11 mm2 (P?=?0.012) in the control and safranal-treated group respectively. The average CNV thickness was 127.4±18.75 and 100.6±17.34 μm (P=0.001) in control and safranal-treated group. Under the condition of oxidative stress, cell proliferation was inhibited by safranal and inhibition rates were 7.4%-35.4% at the different concentrations. For tube formation study, the number of new branches was 364 in control group and 35, 42, and 17 in 20, 40, and 80 μg/mL safranal groups respectively (P<0.01). From the KEGG pathway bubble graph, the PI3K-AKT signaling pathway showed a high gene ratio. The protein expression was elevated of insulin receptor substrate (IRS) and the phosphorylation level of PI3K, phosphoinositide-dependent protein kinase 1/2 (PDK1/2), AKT and Bcl-2 associated death promoter (BAD) was also elevated under oxidative stress condition but inhibited by safranal. CONCLUSION: Safranal can inhibit CNV both in vivo and in vitro, and the IRS-PI3K-PDK1/2-AKT-BAD signaling pathway is involved in the pathogenesis of CNV.http://ies.ijo.cn/en_publish/2021/7/20210704.pdfchoroidal neovascularizationsafranalhuman choroidal microvascular endothelial cellsoxidative stresstranscriptomics |
| spellingShingle | Qin-Xiao Yao-Yao Sun Zhan-Jun Lu Tian-Zi Zhang Shan-Shan Li Ting Hua Suriguga Wen-Lin Chen Lin-Lin Ran Wen-Zhen Yu Fei Yang Burenbatu Inhibitory effects of safranal on laser-induced choroidal neovascularization and human choroidal microvascular endothelial cells and related pathways analyzed with transcriptome sequencing International Journal of Ophthalmology choroidal neovascularization safranal human choroidal microvascular endothelial cells oxidative stress transcriptomics |
| title | Inhibitory effects of safranal on laser-induced choroidal neovascularization and human choroidal microvascular endothelial cells and related pathways analyzed with transcriptome sequencing |
| title_full | Inhibitory effects of safranal on laser-induced choroidal neovascularization and human choroidal microvascular endothelial cells and related pathways analyzed with transcriptome sequencing |
| title_fullStr | Inhibitory effects of safranal on laser-induced choroidal neovascularization and human choroidal microvascular endothelial cells and related pathways analyzed with transcriptome sequencing |
| title_full_unstemmed | Inhibitory effects of safranal on laser-induced choroidal neovascularization and human choroidal microvascular endothelial cells and related pathways analyzed with transcriptome sequencing |
| title_short | Inhibitory effects of safranal on laser-induced choroidal neovascularization and human choroidal microvascular endothelial cells and related pathways analyzed with transcriptome sequencing |
| title_sort | inhibitory effects of safranal on laser induced choroidal neovascularization and human choroidal microvascular endothelial cells and related pathways analyzed with transcriptome sequencing |
| topic | choroidal neovascularization safranal human choroidal microvascular endothelial cells oxidative stress transcriptomics |
| url | http://ies.ijo.cn/en_publish/2021/7/20210704.pdf |
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