Progress in anti-inflammatory effects of escin / 中国药理学与毒理学杂志

ABSTRACT

The fraction of horse chestnut seeds was named escins, which mainly consists of A, B, C, and D escin. Accumulating evidence suggests that escin exerts potent anti-inflammatory and anti-edematous effects. The effects of escin on inflammation and edema have been confirmed in various models. In a study in 1961, intravenous administration of escin was found to reduce acute edema in a rat paw. In the same study, escin was found to inhibit the increase in vascular permeability induced by egg white injection. Escin dose-dependently reduced the capillary permeability in chlo?roform-induced local inflammation in the abdominal skin surface of rabbits. The anti-inflammatory and anti-edematous effects of external use of escin were studied in carrageenan-induced paw edema and histamine-induced capillary perme?ability in rats. Escin gel decreased the contents of PGE2, TNF-α, and IL-1β, and reduced the raw edema and capillary permeability. The carrageenan-induced paw edema and pleuritis in bilaterally adrenalectomized rats were used to inves?tigate the anti-inflammatory effects of escin and glucocorticoid alone or combined. Co-administration of escin with corti?sone significantly reduced the volume of exudates and the number of white blood cells of exudates. The findings sug?gest escin can synergize with glucocorticoids to enhance their anti-inflammatory effect. The anti-inflammatory effect of escin was investigated in carrageenan-induced paw edema and acetic acid-induced capillary permeability in mice. Escin showed an anti-inflammatory effect, which is similar to that seen with dexamethasone treatment. However, escin showed a longer duration of the anti-inflammatory response than that of dexamethasone. Furthermore, escin had no signif?icant effects on spleen index, thymus index , proliferative capacity of splenocytes, lymphocyte count, and phagocytic rate. The findings suggest that escin is a potent anti-inflammatory drug with long-lasting anti-inflammatory effects without any immunosuppressive effects. Traditionally the mechanism of anti-inflammatory effect of escin is supposed to be rela?tive to release of PGF2α and corticosterone. The early studies showed that escin might promote the release of PGF2αand affect the pituitary adrenal system, stimulate the release of adrenocorticotropic hormone (ACTH) and glucocorticoid, which may explain its anti-inflammatory and anti-edema effects. Escin has glucocorticoid-like anti-inflammatory effect. However, escin did not exhibit an anti-inflammatory effect in low dose. Combination of suboptimal concentrations of escin with corticosterone inhibited the release of inflammatory factors including NO, TNF-αand IL-1βin the LPS-stimulated macrophage cells. Previous studies demonstrate that escin combined with glucocorticoid produced synergistic anti-inflammatory effects. The potential synergistic mechanisms may be associated with the property which escin regulates the glucocorticoid receptor (GR) signaling pathway. Escin can upregulate the expression of GR, promote the combina?tion of glucocorticoid and GR, then promote the activated GR transfer into the nucleus. Activated GR will inhibit the acti?vation of NF-κB directly, thus further inhibiting the expression of TNF-αand IL-1βand other inflammatory factors. Escin could inhibit 11β-HSD2 but not 11β-HSD1, thus decrease the metabolism of glucocorticoid. Escin and glucocorticoids have similar chemical structures. This indicate that one of the anti-inflammatory mechanisms of escin may be due to its stimulating GR by binding to it. Eacin might be a partial agonist of GR. A good many of researches have demonstrated the anti-inflammatory properties of escin, and shed light on the underlying mechanisms by which escin exerts these effects. Escin, as an oral or intravenous formulation, or a topical gel, inhibits inflammation, producing measurable improve?ments in edema and acute lung injury. Further clinical studies of escin are needed to demonstrate these properties in larger patient populations.