VEINOTONIC EFFECT, VASCULAR PROTECTION, ANTIINFLAMMATORY AND FREE-RADICAL SCAVENGING PROPERTIES OF HORSE CHESTNUT EXTRACT

Horse chestnut extract (HCE), containing 70% escin, is the main active component of Veinotonyl 75(R). The aim of this work was to investigate pharmacological properties attempting to elucidate the efficacy of HCE in chronic venous insufficiency. Veinotonic and lymphagogue properties: HCE does dependently contracts the canine saphenous isolated vein (cumulative doese 5 10(-5) to 5 . 10(-4) g/ml). Its action lasts more than 5 h. In the perfused canine saphenous vein, HCE (25-50 mg in bolus) increases the venous pressure of the normal vein and the pathological vein stenosed 8 days before, and the contractile response to noradrenaline is significantly potentiated. Moreover, during the perfusion in inverse direction of the blood stream, a clear contracting effect on the valves is also obtained with HCE. In the anaesthetized dog, HCE in situ improves the femoral vein compliance and opposes the venous distension obtained during clamping in a carotido-femoral perfusion with constant flow In other respects, HCE significantly increases femoral venous pressure and flow together with thoracic lymphatic flow while respecting the arterial parameters (2.5 and 5 mg/kg iv.). Vasculotropic action: HCE dose dependently dimishes the cutaneous capillary hyperpermeability induced either by injections of phlogistic agents as histamine and serotonin in the rat (100 to 400 mg/kg p.o.), or by an irritative agent (chloroform) application in the rabbit (50 to 300 mg/kg p.o. and 2.5 to 5 mg/kg i.v.). It significantly increases the vascular resistance in the guinea pig fed a scorbutigenic diet as measured by the petechia method (50 to 400 mg/kg p.o.). Antiedema and antiinflammatory properties: HCE decreases the formation of edemas induced in the rat's hind paw, one of lymphatic origin, the other of inflammatory origin (200 to 400 mg/kg p.o.). In an experimental model of pleurisy in the rat HCE suppresses plasmatic extravasation and leucocytes emigration into the pleural cavity (200 to 400 mg/kg p.o., 1 to 10 mg/kg iv.). It decreases the connective tissue formation in the subchronic model of inflammatory granloma in the rat (400 mg/kg p.o. and 5-10 mg/kg sc). Antiradical mechanism of action both in vitro and in vivo. HCE dose dependently inhibits both enzymatic and non-enzymatic in vitro lipid peroxidation (5 . 10(-6) to 5 . 10(-4) g/ml). In vivo, HCE limits the deleterious action of free oxygenated radicals on cells and surrounding tissues when these free radicals are massively generated in two different protocols to produce tissue damage one by enzymatic production, inducing a local plantar inflammatory reaction, glucose-oxidase induced edema in mice (200-400 mg/kg p.o.), other by production of free radicals formed during the creation of an alloxanic diabetes in the rat (25 mg/kg i.v.). A positive action of HCE could be obtained on the different alteration levels in venous return circulation and allows to partly explain the efficacy of HCE in the chronic venous disease.