Anti-angiogenic Activity of Sclareol: In Vivo and Ex Vivo Study

Abstract

Background: Angiogenesis plays a crucial role in the progression of cancer and other angiogenesis-dependent disorders. Natural products are an important source of novel anti-angiogenic agents. Sclareol, a naturally occurring labdane diterpene, has attracted interest because of its diverse pharmacological properties; however, its anti-angiogenic potential remains poorly understood. Objective: The objective of this study is to investigate the anti-angiogenic activity of sclareol in ex vivo and in vivo models. Methods: Anti-angiogenic activity was investigated ex vivo using the rat aortic ring (RAR) and in vivo chick chorioallantoic membrane (CAM) assays. In the RAR assay, thoracic aortic rings from male albino rats were treated with sclareol (6.25–200 µg/mL). Suramin (100 µg/mL) and 1% DMSO served as positive and negative controls, respectively. Microvessel outgrowth inhibition and the half-maximal inhibitory concentration (IC₅₀) were determined from dose-response analysis. In the CAM assay, fertilized chicken eggs were treated with sclareol (0.25 and 0.5 mg/mL), and anti-angiogenic activity was measured. Results: Sclareol inhibited microvessel outgrowths in a concentration-dependent manner, producing 91.28±1.51% inhibition at 100 µg/mL compared with 98.22±1.22% for suramin (IC₅₀=32.31 µg/mL; p<0.05). In the CAM assay, sclareol inhibited neovascularization with avascular inhibition zones of 10.33±1.75 mm and 7.16±0.75 mm at 0.5 and 0.25 mg/mL, respectively (p<0.01). Conclusions: Sclareol demonstrated potent concentration-dependent anti-angiogenic activity in both ex vivo and in vivo models, indicating its potential as a promising natural anti-angiogenic agent and supporting further investigation for the management of cancer and other angiogenesis-dependent disorders.