Preclinical Studies

The venotonic, antiedema and anti-inflammatory effects and beneficial effects on the balance between connective tissue formation and breakdown have been demonstrated in animal model studies. 13-16 The free radical scavenging action of the standardized extract containing 70% escin have been demonstrated13.

a. Protection against capillary hyperpermeability

Gullaume and Padioleau12 demonstrated the efficacy of orally administered 70% extract in offering protection against capillary hyperpermeability of rat skin induced by serotonin and histamine. In these study the degree of protection was measured by the time required for a dye to penetrate the walls. A dose-dependent protective effect was observed for both inflammatory mediators, with an 80% increase in dye appearance time was observed at a dose of 200 mg/kg of the extract (Figure 1A and 1B). 13

Effect of horse chestnut extract on the protection of rat skin against capillary hyperpermeability induced by serotonin.

Figure 1A. Effect of horse chestnut extract on the protection of rat skin against capillary hyperpermeability induced by serotonin.

Oral treatment 1 hr prior to intradermal injections n=3 to 7 experimental groups per dose, 4 animals each

Figure 1B : Effect of oral HCSE on the increase in capillary permeability of rat skin induced by histamine, expressed as cutaneous dye appearance time. (Oral treatment 1 hr prior to intradermal injections n=3 to 7 experimental groups per dose, 4 animals each.13 )



b. Antiedema and anti-inflammatory properties

Figure 2 shows the significant inhibition of the foot pad swelling induced by carrageenin, measured after 3 hours was observed, which is a suitable time where edema reaction is at its maximum.

Effect of HCSE on carrageenin induced edema in rats The HCSE was administered orally at the time of carrageenin injection

Figure 2 : Effect of HCSE on carrageenin induced edema in rats. The HCSE was administered orally at the time of carrageenin injection.13



c. Carrageenin pleurisy in rats

HCSE was found to significantly and dose-dependently inhibit inflammatory exudation. HCSE administered orally or intravenously inhibited plasmatic exudation at a dose of 5 mg/kg. Leucocyte migration at the local inflammation site was significantly inhibited by oral administration.

Effect of HCSE on carrageenin induced edema in rats The HCSE was administered orally at the time of carrageenin injection

Figure 3 : Effect of daily treatment with HCSE (5 and 10 mg/kg sub cutaneously) on the dry weight of the subcutaneous granulomas obtained 4 days after carrageenin in the rat.13



d. Inhibition of lipid peroxidation and hydroxyradical generation-induced cell damage

HCSE was found to inhibit lipid peroxidation in vitro in a concentration-dependent manner. The IC50 values of α-tocopherol and HCSE were 7.3x10-6 and 1.4x10-4 mol/L respectively, in a non-enzymatic test, whereas an enzymatic test reported an IC50 value of 1.7x10-5 for HCSE while α-tocopherol was inactive.

Oral administration of HCSE significantly reduced local inflammation induced by glucose oxidase injection in mice. The efficacy of HCSE is comparable to the anti-inflammatory effects of phenylbutazone as seen in Figure 4.

Effect of HCSE and phenylbutazone on oxygen free radical mediated paw swelling in mice

Figure 4 : Effect of HCSE and phenylbutazone on oxygen free radical mediated paw swelling in mice.12




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