Effect of curcuminoids as anti-inflammatory agents on the hepatic microvascular response to endotoxin

Curcuminoids, derived from the plant Curcuma domestica Val., have been shown to be free radical scavengers that suppress the production of superoxide by macrophages and potent anti-inflammatory agents that inhibit the lipopolysacharide (LPS)-induced production of tumor necrosis factor alpha (TNFalpha), interleukin (IL)-1beta, and the activation of nuclear factor (NF)-kappaB in human monocytic derived cells. The present study was undertaken to determine the efficacy of curcuminoids in inhibiting the hepatic microvascular inflammatory response elicited by LPS. BALB/C mice were gavaged intragastricly with curcuminoids [40 mg/kg body weight (bw) or 80 mg/kg bw] 1 h before intravenous injection of LPS (Escherichia coli, O111:B4, 100 microg/kg bw). The liver was examined 2 h after LPS injection using in vivo microscopic methods. LPS-treated mice showed significantly increased phagocytic activity of centrilobular Kupffer cells. The numbers of leukocytes adhering to the sinusoidal wall and swollen endothelial cells increased significantly in both the periportal and centrilobular regions, concomitant with a reduction in the numbers of sinusoids containing flow. Pretreatment with curcuminoids at the doses of 40 mg/kg bw or 80 mg/kg bw to endotoxemic mice significantly reduced the phagocytic activity of Kupffer cells, the numbers of adhering leukocytes and swollen endothelial cells. As a result, the number of sinusoids containing flow was increased in animals treated with 40 mg/kg curcuminoids and restored to control levels with 80 mg/kg curcuminoids. Neutrophil sequestration was reduced when measured in sections stained with naphtol AS-D chloroacetate esterase technique. These results demonstrate that curcuminoids are effective in suppressing the hepatic microvascular inflammatory response to LPS and may be a natural alternative anti-inflammatory substance.