Effect of fangchinoline in murine models of multiple organ dysfunction syndrome and septic shock

Objective and Design: To study the effect of the alkaloid fangchinoline on zymosan-induced multiple organ dysfunction syndrome (MODS) and Escherichia coli (E. coli)-induced septic shock. Material: Male ICR mice were used. Macrophages were isolated from peritoneal cavity for in vitro study. Treatment: Fangchinoline was administered i.p. at a dose of 1 or 5 mg/kg into the mice. Methods: MODS was induced by intraperitoneal (i. p.) injection of zymosan at a dose 1.0 or 0.8/g b.w. E. coli-induced septic shock was provoked by i. p. inoculation of 5 x 101 bacterial cells into mice. TNF-alpha in serum and supernatants from peritoneal macrophages was detected by the use of L-929 cell cytotoxic assay. Alternative pathway (AP) complement activity was determined by hemolytic assay. Results: Fangchinoline increased the survival rate in lethal MODS and septic shock. The alkaloid prevented the loss of body weight and liver enlargement in MODS and suppressed serum tumor necrosis factor-alpha (TNF-alpha) accumulation in MODS and septic shock. Conclusions: The result suggest that fangchinoline due mainly to its ability to downregulate TNF-alpha production might have protective effect in murine models of zymosan-induced MODS and E. coli-induced septic shock.