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Shikonin alleviates choroidal neovascularization by inhibiting proangiogenic factor production from infiltrating macrophages.
- Source :
-
Experimental eye research [Exp Eye Res] 2021 Dec; Vol. 213, pp. 108823. Date of Electronic Publication: 2021 Nov 06. - Publication Year :
- 2021
-
Abstract
- Choroidal neovascularization (CNV), a feature of neovasular age-related macular degeneration (AMD), acts as a leading cause of vision loss in the elderly. Shikonin (SHI), a natural bioactive compound extracted from Chinese herb radix arnebiae, exerts anti-inflammatory and anti-angiogenic roles and also acts as a potential pyruvate kinase M2 (PKM2) inhibitor in macrophages. The major immune cells macrophages infiltrate the CNV lesions, where the production of pro-angiognic cytokines from macrophage facilitates the development of CNV. PKM2 contributes to the neovascular diseases. In this study, we found that SHI oral gavage alleviated the leakage, area and volume of mouse laser-induced CNV lesion and inhibited macrophage infiltration without ocular cytotoxicity. Moreover, SHI inhibited the secretion of pro-angiogenic cytokine, including basic fibroblast growth factor (FGF2), insulin-like growth factor-1 (IGF1), chemokine (C-C motif) ligand 2 (CCL2), placental growth factor and vascular endothelial growth factor (VEGF), from primary human macrophages by down-regulating PKM2/STAT3/CD163 pathway, indicating a novel potential therapy strategy for CNV.<br /> (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Subjects :
- Angiogenesis Inducing Agents metabolism
Animals
Antigens, CD metabolism
Antigens, Differentiation, Myelomonocytic metabolism
Blotting, Western
Cells, Cultured
Choroidal Neovascularization enzymology
Chromatography, High Pressure Liquid
Coloring Agents administration & dosage
Cytokines metabolism
Disease Models, Animal
Drugs, Chinese Herbal therapeutic use
Enzyme-Linked Immunosorbent Assay
Fluorescein Angiography
Humans
In Situ Nick-End Labeling
Indocyanine Green administration & dosage
Macrophages enzymology
Male
Mice
Mice, Inbred C57BL
Phosphorylation
Pyruvate Kinase metabolism
Receptors, Cell Surface antagonists & inhibitors
Receptors, Cell Surface metabolism
STAT3 Transcription Factor antagonists & inhibitors
STAT3 Transcription Factor metabolism
Angiogenesis Inhibitors therapeutic use
Anti-Inflammatory Agents, Non-Steroidal therapeutic use
Choroidal Neovascularization drug therapy
Macrophages drug effects
Naphthoquinones therapeutic use
Pyruvate Kinase antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0007
- Volume :
- 213
- Database :
- MEDLINE
- Journal :
- Experimental eye research
- Publication Type :
- Academic Journal
- Accession number :
- 34752817
- Full Text :
- https://doi.org/10.1016/j.exer.2021.108823