Shikonin alleviates choroidal neovascularization by inhibiting proangiogenic factor production from infiltrating macrophages.

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.

• Authors: Ying Wang, Laiqing Xie, Manhui Zhu, Yang Guo, Yuanyuan Tu, Yamei Zhou, Jia Zeng, Linling Zhu, Shu Du, Zhenzhen Wang, Yuting Zhang, Xiaojuan Liu, E Song
• Journal: Experimental eye research (Exp Eye Res) Vol. 213 Pg. 108823 (12 2021) ISSN: 1096-0007 [Electronic] England
• PMID: 34752817 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.

Chemical References

• Angiogenesis Inducing Agents
• Angiogenesis Inhibitors
• Anti-Inflammatory Agents, Non-Steroidal
• Antigens, CD
• Antigens, Differentiation, Myelomonocytic
• CD163 antigen
• Coloring Agents
• Cytokines
• Drugs, Chinese Herbal
• Naphthoquinones
• Receptors, Cell Surface
• STAT3 Transcription Factor
• Stat3 protein, mouse
• shikonin
• Pkm protein, mouse
• Pyruvate Kinase
• Indocyanine Green

Topics

• Angiogenesis Inducing Agents (metabolism)
• Angiogenesis Inhibitors (therapeutic use)
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (therapeutic use)
• Antigens, CD (metabolism)
• Antigens, Differentiation, Myelomonocytic (metabolism)
• Blotting, Western
• Cells, Cultured
• Choroidal Neovascularization (drug therapy, 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 (drug effects, enzymology)
• Male
• Mice
• Mice, Inbred C57BL
• Naphthoquinones (therapeutic use)
• Phosphorylation
• Pyruvate Kinase (antagonists & inhibitors, metabolism)
• Receptors, Cell Surface (antagonists & inhibitors, metabolism)
• STAT3 Transcription Factor (antagonists & inhibitors, metabolism)