Catalpol Protects Against Retinal Ischemia Through Antioxidation, Anti-Ischemia, Downregulation of β-Catenin, VEGF, and Angiopoietin-2 : In Vitro and In Vivo Studies
department or school: Science, Faculty of
department or school: Non UBC
data provider: DSpace
identifier citation: International Journal of Molecular Sciences 26 (9): 4019 (2025)
creator: Chao, Howard Wen-Haur
creator: Chao, Windsor Wen-Jin
creator: Chao, Hsiao-Ming
issued: 2025-05-28T16:16:09Z
issued: 2025-04-24
description: Retinal ischemic disorders present significant threats to vision, characterized by inadequate blood supply oxygen–glucose deprivation (OGD), oxidative stress, and cellular injury, often resulting in irreversible injury. Catalpol, an iridoid glycoside derived from Rehmannia glutinosa, has demonstrated antioxidative and neuroprotective effects. This study aimed at investigating the protective effects and mechanisms of catalpol against oxidative stress or OGD in vitro and retinal ischemia in vivo, focusing on the modulation of key biomarkers of retinal ischemia, including HIF-1α, vascular endothelial growth factor (VEGF), angiopoietin-2, MCP-1, and the Wnt/β-catenin pathway. Cellular viability was assessed using retinal ganglion cell-5 (RGC-5) cells cultured in DMEM; a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed. H2O2 (1 mM)/OGD was utilized. Vehicle or different catalpol concentrations were administered 15 min before the ischemic-like insults. The Wistar rat eyes’ intraocular pressure was increased to 120 mmHg for 60 min to induce retinal ischemia. Intravitreous injections of catalpol (0.5 or 0.25 mM), Wnt inhibitor DKK1 (1 μg/4 μL), anti-VEGF Lucentis (40 μg/4 μL), or anti-VEGF Eylea (160 μg/4 μL) were administered to the rats’ eyes 15 min before or after retinal ischemia. Electroretinogram (ERG), fluorogold retrograde labeling RGC, Western blotting, ELISA, RT-PCR, and TUNEL were utilized. In vitro, both H2O2 and OGD models significantly (p < 0.001/p < 0.001; H2O2 and OGD) induced oxidative stress/ischemic-like insults, decreasing RGC-5 cell viability (from 100% to 55.14 ± 2.19%/60.84 ± 4.57%). These injuries were insignificantly (53.85 ± 1.28% at 0.25 mM)/(63.46 ± 3.30% at 0.25 mM) and significantly (p = 0.003/p = 0.012; 64.15 ± 2.41%/77.63 ± 8.59% at 0.5 mM) altered by the pre-administration of catalpol, indicating a possible antioxidative and anti-ischemic effect of 0.5 mM catalpol. In vivo, catalpol had less effect at 0.25 mM …
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/91209
note: Academic Editor: J. FieldingHejtmancikReceived: 20 February 2025Revised: 7 April 2025Accepted: 7 April 2025Published: 24 April 2025Citation: Chao, H.W.-H.; Chao,W.W.-J.; Chao, H.-M. Catalpol ProtectsAgainst Retinal Ischemia ThroughAntioxidation, Anti-Ischemia,Downregulation ofβ-Catenin, VEGF,and Angiopoietin-2: In Vitro and InVivo Studies. Int. J. Mol. Sci. 2025, 26,4019. https://doi.org/10.3390/ijms26094019Copyright: © 2025 by the authors.Licensee MDPI, Basel, Switzerland.This article is an open access articledistributed under the terms andconditions of the Creative CommonsAttribution (CC BY) license(https://creativecommons.org/licenses/by/4.0/).ArticleCatalpol Protects Against Retinal Ischemia ThroughAntioxidation, Anti-Ischemia, Downregulation of β-Catenin,VEGF, and Angiopoietin-2: In Vitro and In Vivo Studies †Howard Wen-Haur Chao 1,2, Windsor Wen-Jin Chao 1,3 and Hsiao-Ming Chao 4,5,6,*1 Department of Medicine, School of Medicine, Aston University, Birmingham B4 7ET, UK2 Department of Medical Education, Leeds University, Leeds LS2 9JT, UK3 Department of Science, University of British Columbia, Vancouver, BC V6T 1Z4, Canada4 Department of Chinese Medicine, School of Chinese Medicine, China Medical University,Taichung 404, Taiwan5 Institute of Pharmacology, Department of Medicine, School of Medicine,National Yang Ming Chiao Tung University, Taipei 11221, Taiwan6 Department of Ophthalmology, Shin Kong Hospital, Taipei 105, Taiwan* Correspondence: hsiaoming.chao@gmail.com† This study was accepted to perform both a Rapid Fire oral talk and a poster presentation at the26th European Association for Vision and Eye Research (EVER) Congress on 26–28 October 2023at Valencia Conference Center, Spain.Abstract: Retinal ischemic disorders present significant threats to vision, characterizedby inadequate blood supply oxygen–glucose deprivation (OGD), oxidative stress, andcellular injury, often resulting in irreversible injury. Catalpol, an iridoid glycoside de-rived from Rehma…
has type: Article
is shown at: 10.14288/1.0448963
language: eng
peer review status: Reviewed
provider: Vancouver : University of British Columbia Library
publisher: Multidisciplinary Digital Publishing Institute
publisher DOI: 10.3390/ijms26094019
rights: CC BY 4.0
rights URI: https://creativecommons.org/licenses/by/4.0/
scholar level: Faculty
scholar level: Researcher
subject: catalpol
subject: H2O2
subject: OGD
subject: retinal ischemia
subject: neuroprotection
subject: Chinese medicine
subject: β-catenin
subject: VEGF
subject: angiopoietin-2
subject: HIF-1α
subject: MCP-1
type: Text
identifier URI: http://hdl.handle.net/2429/91209