Syringaresinol Alleviates Early Diabetic Retinopathy by Downregulating HIF‐1α/VEGF via Activating Nrf2 Antioxidant Pathway
Scope Early diabetic retinopathy (DR) is characterized by chronic inflammation, excessive oxidative stress, and retinal microvascular damage. Syringaresinol (SYR), as a natural polyphenolic compound, has been proved to inhibit many disease progression due to its antiinflammatory and antioxidant prop...
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| Veröffentlicht in: | Molecular nutrition & food research 2024-02, Vol.68 (4), p.e2200771-n/a |
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| creator | Liu, Chang Cheng, Tianwei Wang, Yufei Li, Guangru Wang, Yachen Tian, Wencong Feng, Lifeng Zhang, Shengzheng Xu, Yang Gao, Yang Li, Jing Liu, Jie Cui, Jianlin Yan, Jie Cao, Lei Pan, Zhongjie Qi, Zhi Yang, Liang |
| description | Scope
Early diabetic retinopathy (DR) is characterized by chronic inflammation, excessive oxidative stress, and retinal microvascular damage. Syringaresinol (SYR), as a natural polyphenolic compound, has been proved to inhibit many disease progression due to its antiinflammatory and antioxidant properties. The present study focuses on exploring the effect of SYR on hyperglycemia‐induced early DR as well as the underlying mechanisms.
Methods and results
Wild‐type (WT) and nuclear factor erythroid 2‐related factor 2 (Nrf2)‐knockout C57BL/6 mice of type 1 diabetes and high glucose (HG)‐induced RF/6A cells are used as in vivo and in vitro models, respectively. This study finds that SYR protects the retinal structure and function in diabetic mice and reduces the permeability and apoptosis of HG‐treated RF/6A cells. Meanwhile, SYR distinctly mitigates inflammation and oxidative stress in vivo and vitro. The retinal microvascular damages are suppressed by SYR via downregulating hypoxia‐inducible factor‐1α (HIF‐1α)/vascular endothelial growth factor (VEGF) pathway. Whereas, SYR‐provided protective effects are diminished in Nrf2‐knockout mice, indicating that SYR improves DR progression by activating Nrf2. Similarly, SYR cannot exert protective effects against HG‐induced oxidative stress and endothelial injury in small interfering RNA (siRNA)‐Nrf2‐transfected RF/6A cells.
Conclusion
In summary, SYR suppresses oxidative stress via activating Nrf2 antioxidant pathway, which ameliorates retinal microvascular damage by downregulating HIF‐1α/VEGF, thereby alleviating early DR progression.
Schematic diagram of the protective effect of syringaresinol (SYR) against retinal microvascular damage of DR in a manner dependent on Nrf2 antioxidant pathway activation. SYR suppresses oxidative stress via activating Nrf2/HO‐1/SOD2 pathway, which ameliorates retinal vascular damage by downregulating HIF‐1α/VEGF pathway, ultimately alleviating DR progression. In addition, SYR controls gliosis and inhibits neuronal apoptosis induced by hyperglycemia. |
| doi_str_mv | 10.1002/mnfr.202200771 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2927211845</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2932870165</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3688-3fe3c2ec0acad35b6e85bf1a1b037fe15a1e34cea76b900b06a3243a429117fd3</originalsourceid><addsrcrecordid>eNqFkc9OGzEQh60KVCjl2mNliUsvCR57_-UY0QSQgFYUuK5mndnUyPGm9i7pHir1EfoqvAgP0Sepo9AcuHDxWDOfP431Y-wDiCEIIY8XrvZDKaQUIs_hDduHDNQgAaV2tneZ7rF3IdwLoUAm6i3bU4VKM5Gk--zXt94bN0dPwbjG8rG19GCwpcAn6G3PPxusqDWaX8fTNUtsv_e8iv1m5TzNO4uxPedn59O_v__A0-Px3eR0yqOCj3VrHjbTK19LPnataX6aGbqWf42aFfbv2W6NNtDhcz1gt9PJzcnZ4OLL6fnJ-GKgVVYUA1WT0pK0QI0zlVYZFWlVA0IlVF4TpAikEk2YZ9VIiEpkqOJHMZEjgLyeqQP2aeNd-uZHR6EtFyZoshYdNV0o5UjmEqBI0ogevUDvm867uF2klCxyAdmaGm4o7ZsQPNXl0psF-r4EUa6DKdfBlNtg4oOPz9quWtBsi_9PIgLJBlgZS_0ruvLyanqdZHmh_gFQ_pui</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2932870165</pqid></control><display><type>article</type><title>Syringaresinol Alleviates Early Diabetic Retinopathy by Downregulating HIF‐1α/VEGF via Activating Nrf2 Antioxidant Pathway</title><source>Wiley Online Library Journals Frontfile Complete</source><creator>Liu, Chang ; Cheng, Tianwei ; Wang, Yufei ; Li, Guangru ; Wang, Yachen ; Tian, Wencong ; Feng, Lifeng ; Zhang, Shengzheng ; Xu, Yang ; Gao, Yang ; Li, Jing ; Liu, Jie ; Cui, Jianlin ; Yan, Jie ; Cao, Lei ; Pan, Zhongjie ; Qi, Zhi ; Yang, Liang</creator><creatorcontrib>Liu, Chang ; Cheng, Tianwei ; Wang, Yufei ; Li, Guangru ; Wang, Yachen ; Tian, Wencong ; Feng, Lifeng ; Zhang, Shengzheng ; Xu, Yang ; Gao, Yang ; Li, Jing ; Liu, Jie ; Cui, Jianlin ; Yan, Jie ; Cao, Lei ; Pan, Zhongjie ; Qi, Zhi ; Yang, Liang</creatorcontrib><description>Scope
Early diabetic retinopathy (DR) is characterized by chronic inflammation, excessive oxidative stress, and retinal microvascular damage. Syringaresinol (SYR), as a natural polyphenolic compound, has been proved to inhibit many disease progression due to its antiinflammatory and antioxidant properties. The present study focuses on exploring the effect of SYR on hyperglycemia‐induced early DR as well as the underlying mechanisms.
Methods and results
Wild‐type (WT) and nuclear factor erythroid 2‐related factor 2 (Nrf2)‐knockout C57BL/6 mice of type 1 diabetes and high glucose (HG)‐induced RF/6A cells are used as in vivo and in vitro models, respectively. This study finds that SYR protects the retinal structure and function in diabetic mice and reduces the permeability and apoptosis of HG‐treated RF/6A cells. Meanwhile, SYR distinctly mitigates inflammation and oxidative stress in vivo and vitro. The retinal microvascular damages are suppressed by SYR via downregulating hypoxia‐inducible factor‐1α (HIF‐1α)/vascular endothelial growth factor (VEGF) pathway. Whereas, SYR‐provided protective effects are diminished in Nrf2‐knockout mice, indicating that SYR improves DR progression by activating Nrf2. Similarly, SYR cannot exert protective effects against HG‐induced oxidative stress and endothelial injury in small interfering RNA (siRNA)‐Nrf2‐transfected RF/6A cells.
Conclusion
In summary, SYR suppresses oxidative stress via activating Nrf2 antioxidant pathway, which ameliorates retinal microvascular damage by downregulating HIF‐1α/VEGF, thereby alleviating early DR progression.
Schematic diagram of the protective effect of syringaresinol (SYR) against retinal microvascular damage of DR in a manner dependent on Nrf2 antioxidant pathway activation. SYR suppresses oxidative stress via activating Nrf2/HO‐1/SOD2 pathway, which ameliorates retinal vascular damage by downregulating HIF‐1α/VEGF pathway, ultimately alleviating DR progression. In addition, SYR controls gliosis and inhibits neuronal apoptosis induced by hyperglycemia.</description><identifier>ISSN: 1613-4125</identifier><identifier>EISSN: 1613-4133</identifier><identifier>DOI: 10.1002/mnfr.202200771</identifier><identifier>PMID: 38356045</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject>Antioxidants ; Apoptosis ; Damage ; Diabetes ; diabetes mellitus ; Diabetes mellitus (insulin dependent) ; Diabetic retinopathy ; Growth factors ; Hyperglycemia ; Hypoxia ; In vivo methods and tests ; Inflammation ; Microvasculature ; NRF2 protein ; Oxidative stress ; Permeability ; Retina ; retinal microvascular damage ; Retinopathy ; siRNA ; Structure-function relationships ; SYR ; Vascular endothelial growth factor</subject><ispartof>Molecular nutrition & food research, 2024-02, Vol.68 (4), p.e2200771-n/a</ispartof><rights>2024 Wiley‐VCH GmbH</rights><rights>2024 Wiley-VCH GmbH.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3688-3fe3c2ec0acad35b6e85bf1a1b037fe15a1e34cea76b900b06a3243a429117fd3</citedby><cites>FETCH-LOGICAL-c3688-3fe3c2ec0acad35b6e85bf1a1b037fe15a1e34cea76b900b06a3243a429117fd3</cites><orcidid>0000-0002-1032-8603</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fmnfr.202200771$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fmnfr.202200771$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38356045$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Chang</creatorcontrib><creatorcontrib>Cheng, Tianwei</creatorcontrib><creatorcontrib>Wang, Yufei</creatorcontrib><creatorcontrib>Li, Guangru</creatorcontrib><creatorcontrib>Wang, Yachen</creatorcontrib><creatorcontrib>Tian, Wencong</creatorcontrib><creatorcontrib>Feng, Lifeng</creatorcontrib><creatorcontrib>Zhang, Shengzheng</creatorcontrib><creatorcontrib>Xu, Yang</creatorcontrib><creatorcontrib>Gao, Yang</creatorcontrib><creatorcontrib>Li, Jing</creatorcontrib><creatorcontrib>Liu, Jie</creatorcontrib><creatorcontrib>Cui, Jianlin</creatorcontrib><creatorcontrib>Yan, Jie</creatorcontrib><creatorcontrib>Cao, Lei</creatorcontrib><creatorcontrib>Pan, Zhongjie</creatorcontrib><creatorcontrib>Qi, Zhi</creatorcontrib><creatorcontrib>Yang, Liang</creatorcontrib><title>Syringaresinol Alleviates Early Diabetic Retinopathy by Downregulating HIF‐1α/VEGF via Activating Nrf2 Antioxidant Pathway</title><title>Molecular nutrition & food research</title><addtitle>Mol Nutr Food Res</addtitle><description>Scope
Early diabetic retinopathy (DR) is characterized by chronic inflammation, excessive oxidative stress, and retinal microvascular damage. Syringaresinol (SYR), as a natural polyphenolic compound, has been proved to inhibit many disease progression due to its antiinflammatory and antioxidant properties. The present study focuses on exploring the effect of SYR on hyperglycemia‐induced early DR as well as the underlying mechanisms.
Methods and results
Wild‐type (WT) and nuclear factor erythroid 2‐related factor 2 (Nrf2)‐knockout C57BL/6 mice of type 1 diabetes and high glucose (HG)‐induced RF/6A cells are used as in vivo and in vitro models, respectively. This study finds that SYR protects the retinal structure and function in diabetic mice and reduces the permeability and apoptosis of HG‐treated RF/6A cells. Meanwhile, SYR distinctly mitigates inflammation and oxidative stress in vivo and vitro. The retinal microvascular damages are suppressed by SYR via downregulating hypoxia‐inducible factor‐1α (HIF‐1α)/vascular endothelial growth factor (VEGF) pathway. Whereas, SYR‐provided protective effects are diminished in Nrf2‐knockout mice, indicating that SYR improves DR progression by activating Nrf2. Similarly, SYR cannot exert protective effects against HG‐induced oxidative stress and endothelial injury in small interfering RNA (siRNA)‐Nrf2‐transfected RF/6A cells.
Conclusion
In summary, SYR suppresses oxidative stress via activating Nrf2 antioxidant pathway, which ameliorates retinal microvascular damage by downregulating HIF‐1α/VEGF, thereby alleviating early DR progression.
Schematic diagram of the protective effect of syringaresinol (SYR) against retinal microvascular damage of DR in a manner dependent on Nrf2 antioxidant pathway activation. SYR suppresses oxidative stress via activating Nrf2/HO‐1/SOD2 pathway, which ameliorates retinal vascular damage by downregulating HIF‐1α/VEGF pathway, ultimately alleviating DR progression. In addition, SYR controls gliosis and inhibits neuronal apoptosis induced by hyperglycemia.</description><subject>Antioxidants</subject><subject>Apoptosis</subject><subject>Damage</subject><subject>Diabetes</subject><subject>diabetes mellitus</subject><subject>Diabetes mellitus (insulin dependent)</subject><subject>Diabetic retinopathy</subject><subject>Growth factors</subject><subject>Hyperglycemia</subject><subject>Hypoxia</subject><subject>In vivo methods and tests</subject><subject>Inflammation</subject><subject>Microvasculature</subject><subject>NRF2 protein</subject><subject>Oxidative stress</subject><subject>Permeability</subject><subject>Retina</subject><subject>retinal microvascular damage</subject><subject>Retinopathy</subject><subject>siRNA</subject><subject>Structure-function relationships</subject><subject>SYR</subject><subject>Vascular endothelial growth factor</subject><issn>1613-4125</issn><issn>1613-4133</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNqFkc9OGzEQh60KVCjl2mNliUsvCR57_-UY0QSQgFYUuK5mndnUyPGm9i7pHir1EfoqvAgP0Sepo9AcuHDxWDOfP431Y-wDiCEIIY8XrvZDKaQUIs_hDduHDNQgAaV2tneZ7rF3IdwLoUAm6i3bU4VKM5Gk--zXt94bN0dPwbjG8rG19GCwpcAn6G3PPxusqDWaX8fTNUtsv_e8iv1m5TzNO4uxPedn59O_v__A0-Px3eR0yqOCj3VrHjbTK19LPnataX6aGbqWf42aFfbv2W6NNtDhcz1gt9PJzcnZ4OLL6fnJ-GKgVVYUA1WT0pK0QI0zlVYZFWlVA0IlVF4TpAikEk2YZ9VIiEpkqOJHMZEjgLyeqQP2aeNd-uZHR6EtFyZoshYdNV0o5UjmEqBI0ogevUDvm867uF2klCxyAdmaGm4o7ZsQPNXl0psF-r4EUa6DKdfBlNtg4oOPz9quWtBsi_9PIgLJBlgZS_0ruvLyanqdZHmh_gFQ_pui</recordid><startdate>202402</startdate><enddate>202402</enddate><creator>Liu, Chang</creator><creator>Cheng, Tianwei</creator><creator>Wang, Yufei</creator><creator>Li, Guangru</creator><creator>Wang, Yachen</creator><creator>Tian, Wencong</creator><creator>Feng, Lifeng</creator><creator>Zhang, Shengzheng</creator><creator>Xu, Yang</creator><creator>Gao, Yang</creator><creator>Li, Jing</creator><creator>Liu, Jie</creator><creator>Cui, Jianlin</creator><creator>Yan, Jie</creator><creator>Cao, Lei</creator><creator>Pan, Zhongjie</creator><creator>Qi, Zhi</creator><creator>Yang, Liang</creator><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7QP</scope><scope>7T5</scope><scope>7T7</scope><scope>7TK</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-1032-8603</orcidid></search><sort><creationdate>202402</creationdate><title>Syringaresinol Alleviates Early Diabetic Retinopathy by Downregulating HIF‐1α/VEGF via Activating Nrf2 Antioxidant Pathway</title><author>Liu, Chang ; Cheng, Tianwei ; Wang, Yufei ; Li, Guangru ; Wang, Yachen ; Tian, Wencong ; Feng, Lifeng ; Zhang, Shengzheng ; Xu, Yang ; Gao, Yang ; Li, Jing ; Liu, Jie ; Cui, Jianlin ; Yan, Jie ; Cao, Lei ; Pan, Zhongjie ; Qi, Zhi ; Yang, Liang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3688-3fe3c2ec0acad35b6e85bf1a1b037fe15a1e34cea76b900b06a3243a429117fd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Antioxidants</topic><topic>Apoptosis</topic><topic>Damage</topic><topic>Diabetes</topic><topic>diabetes mellitus</topic><topic>Diabetes mellitus (insulin dependent)</topic><topic>Diabetic retinopathy</topic><topic>Growth factors</topic><topic>Hyperglycemia</topic><topic>Hypoxia</topic><topic>In vivo methods and tests</topic><topic>Inflammation</topic><topic>Microvasculature</topic><topic>NRF2 protein</topic><topic>Oxidative stress</topic><topic>Permeability</topic><topic>Retina</topic><topic>retinal microvascular damage</topic><topic>Retinopathy</topic><topic>siRNA</topic><topic>Structure-function relationships</topic><topic>SYR</topic><topic>Vascular endothelial growth factor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Chang</creatorcontrib><creatorcontrib>Cheng, Tianwei</creatorcontrib><creatorcontrib>Wang, Yufei</creatorcontrib><creatorcontrib>Li, Guangru</creatorcontrib><creatorcontrib>Wang, Yachen</creatorcontrib><creatorcontrib>Tian, Wencong</creatorcontrib><creatorcontrib>Feng, Lifeng</creatorcontrib><creatorcontrib>Zhang, Shengzheng</creatorcontrib><creatorcontrib>Xu, Yang</creatorcontrib><creatorcontrib>Gao, Yang</creatorcontrib><creatorcontrib>Li, Jing</creatorcontrib><creatorcontrib>Liu, Jie</creatorcontrib><creatorcontrib>Cui, Jianlin</creatorcontrib><creatorcontrib>Yan, Jie</creatorcontrib><creatorcontrib>Cao, Lei</creatorcontrib><creatorcontrib>Pan, Zhongjie</creatorcontrib><creatorcontrib>Qi, Zhi</creatorcontrib><creatorcontrib>Yang, Liang</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular nutrition & food research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Chang</au><au>Cheng, Tianwei</au><au>Wang, Yufei</au><au>Li, Guangru</au><au>Wang, Yachen</au><au>Tian, Wencong</au><au>Feng, Lifeng</au><au>Zhang, Shengzheng</au><au>Xu, Yang</au><au>Gao, Yang</au><au>Li, Jing</au><au>Liu, Jie</au><au>Cui, Jianlin</au><au>Yan, Jie</au><au>Cao, Lei</au><au>Pan, Zhongjie</au><au>Qi, Zhi</au><au>Yang, Liang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Syringaresinol Alleviates Early Diabetic Retinopathy by Downregulating HIF‐1α/VEGF via Activating Nrf2 Antioxidant Pathway</atitle><jtitle>Molecular nutrition & food research</jtitle><addtitle>Mol Nutr Food Res</addtitle><date>2024-02</date><risdate>2024</risdate><volume>68</volume><issue>4</issue><spage>e2200771</spage><epage>n/a</epage><pages>e2200771-n/a</pages><issn>1613-4125</issn><eissn>1613-4133</eissn><abstract>Scope
Early diabetic retinopathy (DR) is characterized by chronic inflammation, excessive oxidative stress, and retinal microvascular damage. Syringaresinol (SYR), as a natural polyphenolic compound, has been proved to inhibit many disease progression due to its antiinflammatory and antioxidant properties. The present study focuses on exploring the effect of SYR on hyperglycemia‐induced early DR as well as the underlying mechanisms.
Methods and results
Wild‐type (WT) and nuclear factor erythroid 2‐related factor 2 (Nrf2)‐knockout C57BL/6 mice of type 1 diabetes and high glucose (HG)‐induced RF/6A cells are used as in vivo and in vitro models, respectively. This study finds that SYR protects the retinal structure and function in diabetic mice and reduces the permeability and apoptosis of HG‐treated RF/6A cells. Meanwhile, SYR distinctly mitigates inflammation and oxidative stress in vivo and vitro. The retinal microvascular damages are suppressed by SYR via downregulating hypoxia‐inducible factor‐1α (HIF‐1α)/vascular endothelial growth factor (VEGF) pathway. Whereas, SYR‐provided protective effects are diminished in Nrf2‐knockout mice, indicating that SYR improves DR progression by activating Nrf2. Similarly, SYR cannot exert protective effects against HG‐induced oxidative stress and endothelial injury in small interfering RNA (siRNA)‐Nrf2‐transfected RF/6A cells.
Conclusion
In summary, SYR suppresses oxidative stress via activating Nrf2 antioxidant pathway, which ameliorates retinal microvascular damage by downregulating HIF‐1α/VEGF, thereby alleviating early DR progression.
Schematic diagram of the protective effect of syringaresinol (SYR) against retinal microvascular damage of DR in a manner dependent on Nrf2 antioxidant pathway activation. SYR suppresses oxidative stress via activating Nrf2/HO‐1/SOD2 pathway, which ameliorates retinal vascular damage by downregulating HIF‐1α/VEGF pathway, ultimately alleviating DR progression. In addition, SYR controls gliosis and inhibits neuronal apoptosis induced by hyperglycemia.</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>38356045</pmid><doi>10.1002/mnfr.202200771</doi><tpages>17</tpages><orcidid>https://orcid.org/0000-0002-1032-8603</orcidid></addata></record> |
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| subjects | Antioxidants Apoptosis Damage Diabetes diabetes mellitus Diabetes mellitus (insulin dependent) Diabetic retinopathy Growth factors Hyperglycemia Hypoxia In vivo methods and tests Inflammation Microvasculature NRF2 protein Oxidative stress Permeability Retina retinal microvascular damage Retinopathy siRNA Structure-function relationships SYR Vascular endothelial growth factor |
| title | Syringaresinol Alleviates Early Diabetic Retinopathy by Downregulating HIF‐1α/VEGF via Activating Nrf2 Antioxidant Pathway |
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