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

BACKGROUND: 5α-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 5α-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 5α-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 5α-Hydroxycostic acid can inhibit abnormal cell proliferation, migration and angiogenesis. Additionally, 5α-Hydroxycostic acid enhances cell adhesion by inhibiting the phosphorylation pathways of VEGFR2 and Tie2. In vivo experiments demonstrated that 5α-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: 5α-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.