SEARCHOTHERophthalmology, retina

other·ophthalmology, retina, preclinical research, biomedical research, endocrinology·PMC10759264

Nanoscale coordination polymer Fe-DMY downregulating Poldip2-Nox4-H 2 O 2 pathway and alleviating diabetic retinopathy

Journal of Pharmaceutical Analysis · 11 authors, 8 centres

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TL;DR

Ultra-small Fe-DMY nano-coordinated polymer particles were synthesized and tested in a streptozotocin-induced diabetic retinopathy rat model and in vitro endothelial cell assays. Fe-DMY NCPs alleviated oxidative stress, reduced retinal vascular leakage and neovascularization, and inhibited the Poldip2-Nox4-H2O2 signaling pathway.

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This preclinical study synthesized ultra-small Fe-DMY nano-coordinated polymer particles by combining the natural flavonoid dihydromyricetin (DMY) with iron ions to address DMY's poor solubility and short half-life. In vivo, streptozotocin-induced diabetic retinopathy rats were treated with high-dose (60 mg/kg) or low-dose (10 mg/kg) Fe-DMY NCPs by gavage every three days over a 14-week intervention period. Fe-DMY NCPs alleviated retinal vascular leakage and neovascularization, scavenged excess ROS, and inhibited the Poldip2-Nox4-H2O2 signaling pathway while downregulating VCAM-1, HIF-1α, and VEGF. Biosafety assessment via hematoxylin and eosin staining of major organs showed no notable pathological changes.

STUDY TYPE

other

SPECIALTY

ophthalmology

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AI pipeline

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ORIGINAL PAPER

PMC10759264

Nanoscale coordination polymer Fe-DMY downregulating Poldip2-Nox4-H 2 O 2 pathway and alleviating diabetic retinopathy

Journal of Pharmaceutical Analysis

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ABSTRACT

Diabetic retinopathy (DR) is a prevalent microvascular complication of diabetes and the leading cause of blindness and severe visual impairment in adults. The high levels of glucose trigger multiple intracellular oxidative stress pathways, such as POLDIP2, resulting in excessive reactive oxygen species (ROS) production and increased expression of vascular cell adhesion molecule-1 (VCAM-1), hypoxia-inducible factor 1α (HIF-1α), and vascular endothelial growth factor (VEGF), causing microvascular dysfunction. Dihydromyricetin (DMY) is a natural flavonoid small molecule antioxidant. However, it exhibits poor solubility in physiological environments, has a short half-life in vivo, and has low oral bioavailability. In this study, we present, for the first time, the synthesis of ultra-small Fe-DMY nano-coordinated polymer particles (Fe-DMY NCPs), formed by combining DMY with low-toxicity iron ions. In vitro and in vivo experiments confirm that Fe-DMY NCPs alleviate oxidative stress-induced damage to vascular endothelial cells by high glucose, scavenge excess ROS, and improve pathological features of DR, such as retinal vascular leakage and neovascularization. Mechanistic validation indicates that Fe-DMY NCPs can inhibit the activation of the Poldip2-Nox4-H 2 O 2 signaling pathway and downregulate vital vascular function indicators such as VCAM-1, HIF-1α, and VEGF. These findings suggest that Fe-DMY NCPs could serve as a safe and effective antioxidant and microangio-protective agent, with the potential as a novel multimeric drug for DR therapy.

CITATION EXPORT

Si-Yu Gui, Xin-Chen Wang, Zhi-Hao Huang et al.. Nanoscale coordination polymer Fe-DMY downregulating Poldip2-Nox4-H2O2 pathway and alleviating diabetic retinopathy. Journal of Pharmaceutical Analysis. (2023). https://doi.org/10.1016/j.jpha.2023.05.002

AUTHORS

11 · 8 CENTRES

Si-Yu Gui, Xin-Chen Wang, Zhi-Hao Huang, Mei-Mei Li, Jia-Hao Wang, Si-Yin Gui, Gan-Hua Zhang, Yao Lu, Li-Ming Tao, Hai-Sheng Qian, Zheng-Xuan Jiang

aDepartment of Ophthalmology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China
bDepartment of Clinical Medicine, The Second School of Clinical Medicine, Anhui Medical University, Hefei, 230032, China
cDepartment of Clinical Medicine, The First School of Clinical Medicine, Anhui Medical University, Hefei, 230032, China
dDepartment of Laboratory, Fengtai County First People's Hospital, Huainan, Anhui, 232101, China
eDepartment of Immunology, The School of Medicine, Anhui University of Technology, Huainan, Anhui, 232100, China
fDepartment of Nursing, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China
gDepartment of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China
hSchool of Biomedical Engineering, Research and Engineering Center of Biomedical Materials, Anhui Medical University, Hefei, 230032, China