Tetrandrine Increased the Survival Rate of Mice with Lipopolysaccharide- Induced Endotoxemia

Backgrounds: Endotoxemia usually causes significant morbidity and mortality, and treatment of endotoxemia is often ineffective. The effects of tetrandrine (a bisbenzylisoquinoline alkaloid) on lipopolysaccharide ( LPS)- induced endotoxemia were investigated in mice. Methods: The peritoneal macrophages were stimulated with LPS and treated with or without tetrandrine. The amounts of tumor necrosis factor (TNF)-alpha, interleukin IL-1 beta, and IL-6, and IL- 10 secreted by peritoneal macrophages were measured by enzymelinked immunosorbent assay. Mice were intraperitoneally injected with LPS to induce endotoxemia and were treated or not treated with oral gavage with 150 mg /kg tetrandrine 1 hour before or after LPS injection. The survival rate of the mice was determined after they were treated with various regiments. The amounts of TNF-alpha, IL -1 beta, IL-6, and IL-10 in the serum of the mice were measured by enzyme-linked immunosorbent assay, and the high mobility group box 1 (HMGB 1) concentration was studied by Western blot analysis. Results: Tetrandrine suppressed the LPS-induced increase of TNF-alpha, IL-1 beta, and HMGB1 secretion by peritoneal macrophages but did not affect the IL-6 and IL-10 concentrations. The animals treated with tetrandrine either 1 hour before or after LPS injection had a 100% survival rate, which was significantly higher than that of the control group (40%) (p = 0.005). The LPS-induced increase in serum TNF-alpha, IL-1 beta, and HMGB1 concentrations was reduced by tetrandrine treatment administered either I hour before or after LPS injection (p< 0.0001). In contrast, tetrandrine prolonged the LPS- induced elevation in serum IL-10 concentrations only mildly changed the serum IL-6 concentrations. Conclusions: Tetrandrine treatment either 1 hour before or 1 hour after LPS injection reduced the mortality rate of the mice with LPS-induced endotoxemia. The effects of tetrandrine on LPS- induced endotoxemia might be related to the suppression of TNF-alpha, IL-1 beta, and HMGB1 concentrations