Guan-Cheng Jiang, Hong-Ye Pan, Lei Gu, Tian-Tian Cheng, Bing-Xue Zhu, Xuan-Qi Wang, Jia-Yu Yu, Feng Zhu, Ming Lin, Jiang-Ning Hu, Xia-Wei Wang
{"title":"菊花提取物通过VEGF和Nrf2通路调节抑制老年性黄斑变性病理性血管生成。","authors":"Guan-Cheng Jiang, Hong-Ye Pan, Lei Gu, Tian-Tian Cheng, Bing-Xue Zhu, Xuan-Qi Wang, Jia-Yu Yu, Feng Zhu, Ming Lin, Jiang-Ning Hu, Xia-Wei Wang","doi":"10.1016/j.jep.2025.120660","DOIUrl":null,"url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Chrysanthemum morifolium has long been utilized in Traditional Chinese Medicine to improve visual acuity and alleviate ocular damage. Although recent pharmacological studies highlight its antioxidant and vasoprotective effects, its efficacy against neovascular processes in age-related macular degeneration (AMD) has not been established.</p><p><strong>Aim of the study: </strong>This study aimed to investigate the therapeutic potential and underlying mechanisms of Chrysanthemum morifolium extract (CME) in managing neovascular AMD, emphasizing its effects on vascular endothelial growth factor (VEGF)-mediated angiogenesis and oxidative stress regulation.</p><p><strong>Materials and methods: </strong>In vitro, ARPE-19 retinal pigment epithelial cells underwent hypoxic and oxidative stress assays to measure VEGF, hypoxia-inducible factor 1-alpha (HIF-1α), and nuclear factor erythroid 2-related factor 2 (Nrf2) pathway activation. Human umbilical vein endothelial cells (HUVECs) were treated with a conditioned medium (CM) from CME-exposed ARPE-19 cells to assess migration, invasion, and tube formation. In vivo therapeutic efficacy was validated in cobalt chloride (CoCl<sub>2</sub>)-induced zebrafish and laser-induced rat choroidal neovascularization (CNV) models.</p><p><strong>Results: </strong>CME significantly attenuated hypoxia- and CoCl<sub>2</sub>-induced upregulation of VEGF and HIF-1α, enhanced Nrf2 signaling, and reduced reactive oxygen species (ROS) in ARPE-19 cells. CME-CM markedly suppressed HUVEC migration, invasion, and angiogenesis. In zebrafish and rat CNV models, CME treatment significantly reduced neovascular lesion area and preserved retinal architecture in a dose-dependent manner, without evident toxicity.</p><p><strong>Conclusions: </strong>CME exerts dual anti-angiogenic and antioxidant effects in AMD models by simultaneously targeting VEGF-driven angiogenesis and oxidative stress, supporting its therapeutic potential as a safe and effective herbal intervention for neovascular AMD.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"120660"},"PeriodicalIF":5.4000,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Chrysanthemum morifolium Extract Attenuates Pathological Angiogenesis of Age-Related Macular Degeneration via VEGF and Nrf2 Pathway Modulation.\",\"authors\":\"Guan-Cheng Jiang, Hong-Ye Pan, Lei Gu, Tian-Tian Cheng, Bing-Xue Zhu, Xuan-Qi Wang, Jia-Yu Yu, Feng Zhu, Ming Lin, Jiang-Ning Hu, Xia-Wei Wang\",\"doi\":\"10.1016/j.jep.2025.120660\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Ethnopharmacological relevance: </strong>Chrysanthemum morifolium has long been utilized in Traditional Chinese Medicine to improve visual acuity and alleviate ocular damage. Although recent pharmacological studies highlight its antioxidant and vasoprotective effects, its efficacy against neovascular processes in age-related macular degeneration (AMD) has not been established.</p><p><strong>Aim of the study: </strong>This study aimed to investigate the therapeutic potential and underlying mechanisms of Chrysanthemum morifolium extract (CME) in managing neovascular AMD, emphasizing its effects on vascular endothelial growth factor (VEGF)-mediated angiogenesis and oxidative stress regulation.</p><p><strong>Materials and methods: </strong>In vitro, ARPE-19 retinal pigment epithelial cells underwent hypoxic and oxidative stress assays to measure VEGF, hypoxia-inducible factor 1-alpha (HIF-1α), and nuclear factor erythroid 2-related factor 2 (Nrf2) pathway activation. Human umbilical vein endothelial cells (HUVECs) were treated with a conditioned medium (CM) from CME-exposed ARPE-19 cells to assess migration, invasion, and tube formation. In vivo therapeutic efficacy was validated in cobalt chloride (CoCl<sub>2</sub>)-induced zebrafish and laser-induced rat choroidal neovascularization (CNV) models.</p><p><strong>Results: </strong>CME significantly attenuated hypoxia- and CoCl<sub>2</sub>-induced upregulation of VEGF and HIF-1α, enhanced Nrf2 signaling, and reduced reactive oxygen species (ROS) in ARPE-19 cells. CME-CM markedly suppressed HUVEC migration, invasion, and angiogenesis. In zebrafish and rat CNV models, CME treatment significantly reduced neovascular lesion area and preserved retinal architecture in a dose-dependent manner, without evident toxicity.</p><p><strong>Conclusions: </strong>CME exerts dual anti-angiogenic and antioxidant effects in AMD models by simultaneously targeting VEGF-driven angiogenesis and oxidative stress, supporting its therapeutic potential as a safe and effective herbal intervention for neovascular AMD.</p>\",\"PeriodicalId\":15761,\"journal\":{\"name\":\"Journal of ethnopharmacology\",\"volume\":\" \",\"pages\":\"120660\"},\"PeriodicalIF\":5.4000,\"publicationDate\":\"2025-09-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of ethnopharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jep.2025.120660\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of ethnopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jep.2025.120660","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Chrysanthemum morifolium Extract Attenuates Pathological Angiogenesis of Age-Related Macular Degeneration via VEGF and Nrf2 Pathway Modulation.
Ethnopharmacological relevance: Chrysanthemum morifolium has long been utilized in Traditional Chinese Medicine to improve visual acuity and alleviate ocular damage. Although recent pharmacological studies highlight its antioxidant and vasoprotective effects, its efficacy against neovascular processes in age-related macular degeneration (AMD) has not been established.
Aim of the study: This study aimed to investigate the therapeutic potential and underlying mechanisms of Chrysanthemum morifolium extract (CME) in managing neovascular AMD, emphasizing its effects on vascular endothelial growth factor (VEGF)-mediated angiogenesis and oxidative stress regulation.
Materials and methods: In vitro, ARPE-19 retinal pigment epithelial cells underwent hypoxic and oxidative stress assays to measure VEGF, hypoxia-inducible factor 1-alpha (HIF-1α), and nuclear factor erythroid 2-related factor 2 (Nrf2) pathway activation. Human umbilical vein endothelial cells (HUVECs) were treated with a conditioned medium (CM) from CME-exposed ARPE-19 cells to assess migration, invasion, and tube formation. In vivo therapeutic efficacy was validated in cobalt chloride (CoCl2)-induced zebrafish and laser-induced rat choroidal neovascularization (CNV) models.
Results: CME significantly attenuated hypoxia- and CoCl2-induced upregulation of VEGF and HIF-1α, enhanced Nrf2 signaling, and reduced reactive oxygen species (ROS) in ARPE-19 cells. CME-CM markedly suppressed HUVEC migration, invasion, and angiogenesis. In zebrafish and rat CNV models, CME treatment significantly reduced neovascular lesion area and preserved retinal architecture in a dose-dependent manner, without evident toxicity.
Conclusions: CME exerts dual anti-angiogenic and antioxidant effects in AMD models by simultaneously targeting VEGF-driven angiogenesis and oxidative stress, supporting its therapeutic potential as a safe and effective herbal intervention for neovascular AMD.
期刊介绍：
The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.
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