5α-Hydroxycostic acid inhibits choroidal neovascularization in rats through a dual signalling pathway mediated by VEGF and angiopoietin 2

作者全名："Lei, Wulong; Xu, Huan; Yao, Hao; Li, Lanjiao; Wang, Menglei; Zhou, Xiyuan; Liu, Xueqin"

作者地址："[Lei, Wulong; Xu, Huan; Yao, Hao; Li, Lanjiao; Wang, Menglei; Zhou, Xiyuan; Liu, Xueqin] Chongqing Med Univ, Dept Gastroenterol, Affiliated Hosp 2, Chongqing 400010, Peoples R China; [Lei, Wulong; Xu, Huan; Yao, Hao] Chongqing Key Lab Ophthalmol, Chongqing 400010, Peoples R China"

通信作者："Zhou, XY; Liu, XQ (通讯作者)，Chongqing Med Univ, Dept Gastroenterol, Affiliated Hosp 2, Chongqing 400010, Peoples R China."

来源：MOLECULAR MEDICINE

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001095290500001

JCR分区：Q1

影响因子：5.7

年份：2023

卷号：29

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Choroidal neovascularization; 5 alpha-Hydroxycostic acid; VEGF; VEGFR2; Angiopoietin 2

摘要："Background: 5 alpha-Hydroxycostic acid is a eudemane sesquiterpene that is isolated from the natural plant, Laggera alata. It exerts anti-inflammatory and anti-angiogenic effects on human breast cancer cells, but its role and underlying mechanism in choroidal neovascularization (CNV) are still unclear. We conducted a study to verify that 5 alpha-Hydroxycostic acid can inhibit the formation and leakage of CNV, and describe the possible dual pathway by which it exerts its inhibitory effects in this process.Methods: An in vitro model of choroidal neovascularization was established using VEGF164, while a rat model of choroidal neovascularization was established using a 532 nm laser. In both models, the effects of 5 alpha-Hydroxycostic acid in vivo and in vitro were evaluated to determine its inhibitory effect on abnormal cell proliferation, migration and tubule formation, as well as its effect on pathological changes in choroidal tissues and the area of neovascularization leakage in rats. The levels of components in the VEGF/VEGFR and Ang2/Tie2 signaling pathways were measured in tissues and cells.Results: In vitro experiments have shown that 5 alpha-Hydroxycostic acid can inhibit abnormal cell proliferation, migration and angiogenesis. Additionally, 5 alpha-Hydroxycostic acid enhances cell adhesion by inhibiting the phosphorylation pathways of VEGFR2 and Tie2. In vivo experiments demonstrated that 5 alpha-Hydroxycostic acid has a positive therapeutic effect on choroidal neovascularization in rats. It can effectively reduce vascular leakage, consistent with the results of the cell experiments.Conclusion: 5 alpha-Hydroxycostic acid can inhibit choroidal neovascularization by interfering with the VEGF- and Ang2/Tie2-related pathways, and it may be a good candidate drug for treating CNV."

基金机构：We express our gratitude to the staff of the Chongqing Key Laboratory of Ophthalmology for their kind help during the study.

基金资助正文：We express our gratitude to the staff of the Chongqing Key Laboratory of Ophthalmology for their kind help during the study.