Dietary Compound Chrysin Inhibits Retinal Neovascularization with Abnormal Capillaries in db/db Mice

Diabetic retinopathy (DR) develops in a significant proportion of patients with chronic diabetes, characterized by retinal macular edema and abnormal retinal vessel outgrowth leading to vision loss. Chrysin, a naturally-occurring flavonoid found in herb and honeycomb, has anti-inflammatory, antioxid...

Descripción completa

Detalles Bibliográficos
Autores principales: Kang, Min-Kyung, Park, Sin-Hye, Kim, Yun-Ho, Lee, Eun-Jung, Antika, Lucia Dwi, Kim, Dong Yeon, Choi, Yean-Jung, Kang, Young-Hee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5188437/
https://www.ncbi.nlm.nih.gov/pubmed/27918469
http://dx.doi.org/10.3390/nu8120782
_version_ 1782487033886801920
author Kang, Min-Kyung
Park, Sin-Hye
Kim, Yun-Ho
Lee, Eun-Jung
Antika, Lucia Dwi
Kim, Dong Yeon
Choi, Yean-Jung
Kang, Young-Hee
author_facet Kang, Min-Kyung
Park, Sin-Hye
Kim, Yun-Ho
Lee, Eun-Jung
Antika, Lucia Dwi
Kim, Dong Yeon
Choi, Yean-Jung
Kang, Young-Hee
author_sort Kang, Min-Kyung
collection PubMed
description Diabetic retinopathy (DR) develops in a significant proportion of patients with chronic diabetes, characterized by retinal macular edema and abnormal retinal vessel outgrowth leading to vision loss. Chrysin, a naturally-occurring flavonoid found in herb and honeycomb, has anti-inflammatory, antioxidant, and anti-cancer properties. This study sought to determine the protective effects of chrysin on retinal neovascularization with abnormal vessels and blood-retinal barrier (BRB) breakdown in 33 mM glucose-exposed human retinal endothelial cells and in db/db mouse eyes. High glucose caused retinal endothelial apoptotic injury, which was inhibited by submicromolar chrysin. This compound diminished the enhanced induction of HIF-1α, vascular endothelial growth factor (VEGF), and VEGF receptor-2 (VEGFR2) in high glucose-exposed retinal endothelial cells. Consistently, oral administration of 10 mg/kg chrysin reduced the induction of these proteins in db/db mouse eye tissues. In addition, chrysin restored the decrement of VE-cadherin and ZO-1 junction proteins and PECAM-1 in hyperglycemia-stimulated retinal endothelial cells and diabetic mouse retina, possibly maintaining tight cell-cell interactions of endothelial cells and pericytes. Anti-apoptotic chrysin reduced the up-regulation of Ang-1, Ang-2, and Tie-2 crucial to retinal capillary occlusion and BRB permeability. Furthermore, orally treating chrysin inhibited acellular capillary formation, neovascularization, and vascular leakage observed in diabetic retinas. These observations demonstrate, for the first time, that chrysin had a capability to encumber diabetes-associated retinal neovascularization with microvascular abnormalities and BRB breakdown.
format Online
Article
Text
id pubmed-5188437
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-51884372017-01-03 Dietary Compound Chrysin Inhibits Retinal Neovascularization with Abnormal Capillaries in db/db Mice Kang, Min-Kyung Park, Sin-Hye Kim, Yun-Ho Lee, Eun-Jung Antika, Lucia Dwi Kim, Dong Yeon Choi, Yean-Jung Kang, Young-Hee Nutrients Article Diabetic retinopathy (DR) develops in a significant proportion of patients with chronic diabetes, characterized by retinal macular edema and abnormal retinal vessel outgrowth leading to vision loss. Chrysin, a naturally-occurring flavonoid found in herb and honeycomb, has anti-inflammatory, antioxidant, and anti-cancer properties. This study sought to determine the protective effects of chrysin on retinal neovascularization with abnormal vessels and blood-retinal barrier (BRB) breakdown in 33 mM glucose-exposed human retinal endothelial cells and in db/db mouse eyes. High glucose caused retinal endothelial apoptotic injury, which was inhibited by submicromolar chrysin. This compound diminished the enhanced induction of HIF-1α, vascular endothelial growth factor (VEGF), and VEGF receptor-2 (VEGFR2) in high glucose-exposed retinal endothelial cells. Consistently, oral administration of 10 mg/kg chrysin reduced the induction of these proteins in db/db mouse eye tissues. In addition, chrysin restored the decrement of VE-cadherin and ZO-1 junction proteins and PECAM-1 in hyperglycemia-stimulated retinal endothelial cells and diabetic mouse retina, possibly maintaining tight cell-cell interactions of endothelial cells and pericytes. Anti-apoptotic chrysin reduced the up-regulation of Ang-1, Ang-2, and Tie-2 crucial to retinal capillary occlusion and BRB permeability. Furthermore, orally treating chrysin inhibited acellular capillary formation, neovascularization, and vascular leakage observed in diabetic retinas. These observations demonstrate, for the first time, that chrysin had a capability to encumber diabetes-associated retinal neovascularization with microvascular abnormalities and BRB breakdown. MDPI 2016-12-03 /pmc/articles/PMC5188437/ /pubmed/27918469 http://dx.doi.org/10.3390/nu8120782 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kang, Min-Kyung
Park, Sin-Hye
Kim, Yun-Ho
Lee, Eun-Jung
Antika, Lucia Dwi
Kim, Dong Yeon
Choi, Yean-Jung
Kang, Young-Hee
Dietary Compound Chrysin Inhibits Retinal Neovascularization with Abnormal Capillaries in db/db Mice
title Dietary Compound Chrysin Inhibits Retinal Neovascularization with Abnormal Capillaries in db/db Mice
title_full Dietary Compound Chrysin Inhibits Retinal Neovascularization with Abnormal Capillaries in db/db Mice
title_fullStr Dietary Compound Chrysin Inhibits Retinal Neovascularization with Abnormal Capillaries in db/db Mice
title_full_unstemmed Dietary Compound Chrysin Inhibits Retinal Neovascularization with Abnormal Capillaries in db/db Mice
title_short Dietary Compound Chrysin Inhibits Retinal Neovascularization with Abnormal Capillaries in db/db Mice
title_sort dietary compound chrysin inhibits retinal neovascularization with abnormal capillaries in db/db mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5188437/
https://www.ncbi.nlm.nih.gov/pubmed/27918469
http://dx.doi.org/10.3390/nu8120782
work_keys_str_mv AT kangminkyung dietarycompoundchrysininhibitsretinalneovascularizationwithabnormalcapillariesindbdbmice
AT parksinhye dietarycompoundchrysininhibitsretinalneovascularizationwithabnormalcapillariesindbdbmice
AT kimyunho dietarycompoundchrysininhibitsretinalneovascularizationwithabnormalcapillariesindbdbmice
AT leeeunjung dietarycompoundchrysininhibitsretinalneovascularizationwithabnormalcapillariesindbdbmice
AT antikaluciadwi dietarycompoundchrysininhibitsretinalneovascularizationwithabnormalcapillariesindbdbmice
AT kimdongyeon dietarycompoundchrysininhibitsretinalneovascularizationwithabnormalcapillariesindbdbmice
AT choiyeanjung dietarycompoundchrysininhibitsretinalneovascularizationwithabnormalcapillariesindbdbmice
AT kangyounghee dietarycompoundchrysininhibitsretinalneovascularizationwithabnormalcapillariesindbdbmice