title: Dietary Compound Chrysin Inhibits Retinal Neovascularization with Abnormal Capillaries in db/db Mice.
abstract: 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.
authors.affiliation: Department of Food Science and Nutrition, Hallym University, Chuncheon 24252, Korea. mitholy@hallym.ac.kr.
authors.forename: Min-Kyung
authors.initials: MK
authors.lastname: Kang
authors.affiliation: Department of Food Science and Nutrition, Hallym University, Chuncheon 24252, Korea. sinhyepark@hallym.ac.kr.
authors.forename: Sin-Hye
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Food Science and Nutrition, Hallym University, Chuncheon 24252, Korea. royalskim@hallym.ac.kr.
authors.forename: Yun-Ho
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Food Science and Nutrition, Hallym University, Chuncheon 24252, Korea. reydmswjd@naver.com.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Department of Food Science and Nutrition, Hallym University, Chuncheon 24252, Korea. lucia.dwiantika@gmail.com.
authors.forename: Lucia Dwi
authors.initials: LD
authors.lastname: Antika
authors.affiliation: Department of Food Science and Nutrition, Hallym University, Chuncheon 24252, Korea. ehddus3290@naver.com.
authors.forename: Dong Yeon
authors.initials: DY
authors.lastname: Kim
authors.affiliation: Department of Food Science and Nutrition, Hallym University, Chuncheon 24252, Korea. yjchoi79@hallym.ac.kr.
authors.forename: Yean-Jung
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: Department of Food Science and Nutrition, Hallym University, Chuncheon 24252, Korea. yhkang@hallym.ac.kr.
authors.forename: Young-Hee
authors.initials: YH
authors.lastname: Kang
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis; D015820:Cadherins / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000139:chemically induced / Q000188:drug therapy; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology*; D005947:Glucose; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D042787:Receptor, TIE-2 / Q000378:metabolism; D015861:Retinal Neovascularization / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D012259:Ribonuclease, Pancreatic / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000378:metabolism; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D005419:Flavonoids; D005947:Glucose; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042787:Receptor, TIE-2; D012259:Ribonuclease, Pancreatic; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; D062826:Zonula Occludens-1 Protein; D000099152:Cadherin 5; C497443:Hif1a protein, mouse; C569043:Tjp1 protein, mouse; C467480:vascular endothelial growth factor A, mouse; C043561:chrysin; C000592875:Kdr protein, mouse; C079086:Tek protein, mouse; C046366:angiogenin; C099439:Ang2 protein, mouse
keywords: angiogenesis; blood retinal barrier; chrysin; diabetic retinopathy; retinal neovascularization