Dihydroarteannuin ameliorates lupus symptom of BXSB mice by inhibiting production of TNF-alpha and blocking the signaling pathway NF-kappa B translocation

The aim of this study was to investigate the mechanisms of action of Dihydroarteannuin (DHA), a semi-synthesized agent from the starting material artemisinin extracted from the Chinese Traditional Herbs Artemisia annua, on ameliorating the symptoms of lupus on BXSB mice. The concentration of TNF-alpha in the culture supernatant of the peritoneal macrophages and in the sera of BXSB mice was determined by the ELISA method. NF-kappa B protein expression and translocation were assayed by the EMSA method and laser confocal scanning microscopy method, respectively. I kappa B-alpha and NF-kappa B p65 protein expression were determined by the Western blot method. Renal tissue of the BXSB mice was prepared for assaying inhibitory activity of DHA on NF-kappa B, p65 and I kappa B-alpha protein expression in vivo. The peritoneal macrophages were prepared for analysis inhibitory effects of DHA on translocation of NF-kappa B into nuclear in vitro. We found that DHA strongly reduced the production of TNF-alpha in the culture supernatant of the peritoneal macrophages and in the sera of BXSB mice in vitro or in vivo. The results demonstrated that DHA decreased the expression of NF-kappa B subunit p65 protein and the activation of NF-kappa B in the renal tissue of BXSB mice in vivo. DHA effectively inhibited the nuclear translocation of NF-kappa B in peritoneal macrophages of BXSB mice in vitro. Furthermore, it was demonstrated that the degradation of I kappa B-alpha protein was significantly inhibited by DHA. These observations suggested that the inhibitory effects of DRA on TNF-alpha production may result from the block in the NF-kappa B signaling pathway upstream of I kappa B degradation. (c) 2006 Elsevier B.V. All rights reserved.