ESCULENTOSIDE-A INHIBITS TUMOR-NECROSIS-FACTOR, INTERLEUKIN-1, AND INTERLEUKIN-6 PRODUCTION INDUCED BY LIPOPOLYSACCHARIDE IN MICE

Esculentoside A, a kind of saponin isolated from the root of the Chine se herb Phytolaca esculenta, is reported to possess potent anti-inflam matory effects in acute and chronic experimental models. In the presen t study, we investigated the effects of esculentoside A on the product ion of tumor necrosis factor (TNF), interleukin-1 (IL-1) and interleuk in-6 (IL-6) induced by lipopolysaccharide (LPS) in mice. In vitro expe riments demonstrated that esculentoside A (0.1-10 mu mol/l) significan tly reduced the release of TNF from the peritoneal macrophages derived from mice pretreated with thioglycolate. IL-1 and IL-6 secretion was also obviously inhibited in a concentration-dependent manner by escule ntoside A from 0.01 to 10 mu mol/l. In vivo experiments demonstrated t hat detectable TNF was observed 0.25 h after injection, was maximal at 0.5 h, and returned to baseline at 4 h. Maximal production of IL-1 an d IL-6 were observed to be 1 and 2 h, respectively, after injection of LPS. Pretreatment of mice with 5, 10, or 20 mg/kg esculentoside A onc e a day for 7 consecutive days dose-dependently decreased the TNF, IL- 1 and IL-6 levels in the sera of mice following LPS challenge. TNF, IL -1, and IL-6 are important cytokines involved in the pathogenesis of i nflammatory lesions. Inhibition of inflammatory cytokine production ma y contribute to the anti-inflammatory effects of esculentoside A.