Lu Hongyi, Cai Qi, Li Lele, Gu Jiayi, Zhang Yuting, Sun Haotian, Su Hui, Song Lei
Department of Pediatrics, Nantong First People's Hospital (The Second Affiliated Hospital of Nantong University), Nantong, Jiangsu, China.
Department of Ophthalmology, Nantong First People's Hospital (The Second Affiliated Hospital of Nantong University), Nantong, Jiangsu, China.
J Cell Mol Med. 2024 Dec;28(23):e70228. doi: 10.1111/jcmm.70228.
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).
抗血管内皮生长因子（VEGF）药物可抑制脉络膜新生血管形成（CNV），从而改善视力。然而，一些患者可能对抗VEGF药物反应不佳或产生耐药性。香叶木素（GE）是从草药苦味叶下珠中分离出的一种多酚，具有抗血管生成特性。本研究旨在探讨GE在CNV中的作用机制。研究发现，GE在体外可激活缺氧人脉络膜内皮细胞（HCECs）中的血管紧张素转换酶2（ACE2）/血管紧张素1-7（Ang-[1-7]）/MAS1原癌基因、G蛋白偶联受体（MasR）/白细胞介素-10（IL-10）通路，在体内激光诱导的CNV小鼠模型中也可激活该通路。GE激活ACE2/Ang-(1-7)/MasR/IL-10通路可减弱缺氧HCECs的增殖、迁移和管形成能力，并预防小鼠CNV的发生。值得注意的是，GE对患有CNV的小鼠未造成眼部或全身毒性。这些发现表明，GE通过激活脉络膜内皮细胞（CECs）中的ACE2/Ang-(1-7)/MasR/IL-10通路来减轻CNV。
