Herbal remedies, such as horsechestnut (Aesculus hippocastanum), have been used as medical treatments since the beginning of civilization. Its active ingredient, escin, despite the broad use, as the remedy for a chronic venous insufficiency, it has not undergone careful scientific assessment. This is probably due to the fact that escin is a mixture of triterpene saponins and the analysis of cellular responses following its administration may vary depending on the preparation. It is well established that endothelial cell activation caused by exposure to the hypoxic conditions, such as occur during blood stasis in chronic venous insufficiency patients, triggers inflammatory response in the vein. In the search for well-defined and effective venotropic drug with minimum side effects, we will employ several in vitro techniques assessing endothelial cell function. These will include analysis of endothelial cell activation, via assessment of various signaling pathways, gene activation and protein expression. We assume that such in vitro tests may provide sufficient data to choose best drug candidates to perform in vivo assay using murine model of chronic venous insufficiency. Histological techniques will be then used to evaluate the efficacy of newly synthesized escin derivatives as endothelial cell protective agents. The final stage of preclinical studies will focus on pharmacological properties and toxicological characteristics of tested compounds.

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