Geraniin Alleviates Mouse Laser‐Induced Choroidal Neovascularisation by Inhibiting Choroidal Endothelial Cell ACE2/Ang‐(1–7)/MasR/IL‐10 Pathway

• Published in: Journal of cellular and molecular medicine 2024-12, Vol.28 (23), p.e70228-n/a
• Main Authors: Lu, Hongyi, Cai, Qi, Li, Lele, Gu, Jiayi, Zhang, Yuting, Sun, Haotian, Su, Hui, Song, Lei
• Format: Article
• Language: English
• Subjects: ACE2; Angiogenesis; Angiotensin; Angiotensin I - metabolism; Angiotensin I - pharmacology; Angiotensin-converting enzyme 2; Angiotensin-Converting Enzyme 2 - metabolism; Animal models; Animals; Antibiotics; Antibodies; Cell culture; Cell Movement - drug effects; Cell Proliferation - drug effects; Choroid - drug effects; Choroid - metabolism; Choroid - pathology; choroidal endothelial cells; choroidal neovascularisation; Choroidal Neovascularization - drug therapy; Choroidal Neovascularization - etiology; Choroidal Neovascularization - metabolism; Choroidal Neovascularization - pathology; Disease Models, Animal; Drug resistance; Endothelial cells; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Enzymes; Geraniin; Glucosides - pharmacology; Humans; Hydrolyzable Tannins; Hypoxia; Interleukin-10 - metabolism; interleukin‐10; Laboratory animals; Lasers; Lasers - adverse effects; Liver cancer; Male; Medical imaging; Mice; Mice, Inbred C57BL; Ophthalmology; Original; Peptide Fragments - metabolism; Peptide Fragments - pharmacology; Peptidyl-Dipeptidase A - metabolism; Polymerase chain reaction; Proto-Oncogene Mas; Proto-Oncogene Proteins - metabolism; Receptors, G-Protein-Coupled - metabolism; Retina; Signal Transduction - drug effects; Toxicity; Vascular endothelial growth factor
• ISSN: 1582-1838; 1582-4934; 1582-4934
• DOI: 10.1111/jcmm.70228

ABSTRACT Anti‐vascular endothelial growth factor (VEGF) drugs suppress choroidal neovascularisation (CNV), thus improving vision. However, some patients may have a poor response or develop resistance to anti‐VEGF drugs. Geraniin (GE), a polyphenol isolated from an herb called Phyllanthus amarus, possesses anti‐angiogenic properties. This study aimed to explore the mechanism of action of GE in CNV. GE was found to activate the angiotensin‐converting enzyme 2 (ACE2)/angiotensin 1–7 (Ang‐[1–7])/MAS1 proto‐oncogene, G protein‐coupled receptor (MasR)/interleukin‐10 (IL‐10) pathway in hypoxic human choroidal endothelial cells (HCECs) in vitro and mouse models of laser‐induced CNV in vivo. Activation of the ACE2/Ang‐(1–7)/MasR/IL‐10 pathway by GE attenuated the proliferative, migratory, and tube‐forming abilities of hypoxic HCECs and prevented the development of CNV in mice. Notably, GE did not cause ocular or systemic toxicity in mice with CNV. These findings suggest that GE alleviates CNV by activating the ACE2/Ang‐(1–7)/MasR/IL‐10 pathway in choroidal endothelial cells (CECs).